Gastroenterology Today Autumn 2023

Volume 34 No. 3 Autumn 2023
THE BEST DEFENCE IS
DEFENDO
DEFENDO TM sterile single use valves eliminate
the need for manual cleaning and reprocessing

RReeebmeeeddedddduuuuuuuucccccccaiiiiiiiinnnnnningogggggf yyyytyoooooooouuuuuuuurrerrrrrf wwwwwwwaaaaaaaaiiiiiiiittttttttiiiiiiiinnnnnningogggggf llllklliiiiiiiissssssssttttttttssssssssf aaaaaaaannnnnninddeddddf
iiiiiiiime mmmmmppppppparrerrrrroooooooovvvvvviiiiiiiinnnnnningogggggf pppppppaaaaaaaaattttttttiiiiiiiieeebmeeennnnnninttttttttf eeebmeeexxxpppppppaeeebmeeerrerrrrriiiiiiiieeebmeeennnnnnincccccccaeeebmeee
18f WWeeeeeesleeeeeeslkf Suuuuppppppppppppppoocooooorrrrerrrtttcntttf iiiiiiiisssassssf tttcnttthhhheeeeeeslf UK’ssssssssf llllklleeebmeeeaaaaaaaaddeddddiiiiiiiinnnnnningogggggf iiiiiiiinnnnnninssssssssoooooooouuuuuuuurrerrrrrcccccccaiiiiiiiinnnnnningogggggf
ppppppparrerrrrroooooooovvvvvviiiiiiiiddeddddeeebmeeerrerrrrr..
WWeeeeeeslf sssassssuuuuppppppppppppppoocooooorrrrerrrtttcntttf NHSf ttttttttrrerrrrruuuuuuuussssssssttttttttssssssssf mbyyf ppppppprrrrerrroocooooovviiiiiiiiddddiiiiiiiinnonnnnngggf eeeeeeslxpppppppeeeeeeslrrrrerrriiiiiiiieeeeeeslnnonnnnncca ccceeeeeeslddddf
ccaccplllliiiiiiiinnonnnnniiiiiiiiccaccaaateaaapllllfsssasssstttcntttaaateaaafftttcntttoocooooofrrerrrrreeebmeeeddedddduuuuuuuucccccccaeeebmeeefmbbaaaaaaaacccccccakkkkcllllklloooooooogogggggr,gfiiiiiiiinnnnnnincccccccarrerrrrreeebmeeeaaaaaaaasssssssseeebmeeefcccccccaaaaaaaaapppppppaaaaaaaaacccccccaiiiiiiiittttttttyyyytyy
aaateaaannonnnnnddddf ppppppprrrrerrroocooooovviiiiiiiiddddeeeeeeslf mbb eeebmeeetttttttttttttttteeebmeeerrerrrrrf pppppppaaaaaaaaattttttttiiiiiiiieeebmeeennnnnninttttttttf eeebmeeexxxpppppppaeeebmeeerrerrrrriiiiiiiieeebmeeennnnnnincccccccaeeebmeeef tttcntttrrrrerrreeeeeeslaaateaaatttcntttiiiiiiiinnonnnnngggf
pppppppaaateaaatttcntttiiiiiiiieeeeeeslnnonnnnntttcntttsssassssf iiiiiiiinnonnnnnf tttcnttthhhheeeeeesliiiiiiiirrrrerrrf tttcntttrrrrerrruuuusssasssstttcntttsssassss..
WWhhhhyyf cca ccchhhhoocooooooocooooosssasssseeeeeeslf iiiiiiiinnnnnninssssssssoooooooouuuuuuuurrerrrrrcccccccaiiiiiiiinnnnnningogggggf foooooooorrerrrrrf yyyytyoooooooouuuuuuuurrerrrrrf TTTTrrerrrrruuuuuuuussssssssttttttttr
Meeeeeesleeeeeesltttcntttf yyoocooooouuuurrrrerrrf RRTTTTTTTTf ttttttttaaaaaaaarrerrrrrgogggggeeebmeeettttttttssssssss
Innonnnnncca cccrrrrerrreeeeeeslaaateaaasssasssseeeeeeslf ppppppparrerrrrrooooooooddedddduuuuuuuucccccccattttttttiiiiiiiivvvvvviiiiiiiittttttttyyyyty
Geeeeeesltttcntttf vvvvvvaaaaaaaallllklluuuuuuuueeebmeeef foooooooorrerrrrrf me mmmmmoooooooonnnnnnineeebmeeeyyyyty
WWhhhhyyf woocooooorrrrerrrkf wiiiiiiiitttcnttthhhhf 18f WWeeeeeesleeeeeeslkf Suuuuppppppppppppppoocooooorrrrerrrtttcntttf aaateaaasssassssf aaateaaaf cccccccallllklliiiiiiiinnnnnniniiiiiiiicccccccaaaaaaaaallllkllf
ssssssssttttttttaaaaaaaafff me mmmmmeeebmeeeme mmmmmmbb eeebmeeerrerrrrrr
Eaaateaaarrrrerrrnnonnnnnf eeebmeeexxxttttttttrrerrrrraaaaaaaaf me mmmmmoooooooonnnnnnineeebmeeeyyyyty
Fiiiiiiiinnonnnnnddddf fllllklleeebmeeexxxiiiiiiiimbb llllklleeebmeeef sssssssshhiiiiiiiitfssssssssf aaateaaacca ccccca cccoocooooorrrrerrrddddiiiiiiiinnonnnnngggf tttcntttoocooooof yyoocooooouuuurrrrerrrf sssasssscca ccchhhheeeeeesldddduuuuplllleeeeeesl
TTTTrrerrrrraaaaaaaavvvvvveeebmeeellllkllf aaateaaacca cccrrrrerrroocooooosssasssssssassssf tttcnttthhhheeeeeeslf UK
Foocooooorrrrerrrf mmmoocooooorrrrerrreeeeeeslf iiiiiiiinnonnnnnfoocooooorrrrerrre mmmaaateaaatttcntttiiiiiiiioocooooonnonnnnnf oocooooonnonnnnnf hhhhoocooooowf tttcntttoocoooooy
wwwwwwwoooooooorrerrrrrkkkkcf wwwwwwwiiiiiiiitttttttthhf yyyytyoooooooouuuuuuuurrerrrrrf TTTTrrerrrrruuuuuuuussssssssttttttttr,gf pppppppplllleeeeeeslaaateaaasssasssseeeeeeslf eeeeeesle mmmaaateaaaiiiiiiiipllll
mbb uuuuuuuussssssssddeddddeeebmeeevvvvvv@@1188wwwwwwweeebmeeeeeebmeeekkkkcssssssssuuuuuuuupppppppapppppppaoooooooorrerrrrrtttttttt...cccccccaoooooooome mmmmm
Toocooooof rrrrerrreeeeeeslgggiiiiiiiisssasssstttcnttteeeeeeslrrrrerrrf tttcntttoocooooof wwwwwwwoooooooorrerrrrrkkkkcf wwwwwwwiiiiiiiitttttttthhf uuuuuuuussssssssf aaaaaaaassssssssf aaaaaaaay
cccccccallllklliiiiiiiinnnnnniniiiiiiiicccccccaaaaaaaaallllkllf ssssssssttttttttaaaaaaaafff mmmeeeeeesle mmmmbeeeeeeslrrrrerrrr,gf pppppppplllleeeeeeslaaateaaasssasssseeeeeeslf cca cccoocooooonnonnnnntttcntttaaateaaacca ccctttcnttt
rrerrrrreeebmeeecccccccarrerrrrruuuuuuuuiiiiiiiittttttttme mmmmmeeebmeeennnnnnintttttttt...tttttttteeebmeeeaaaaaaaame mmmmm@@1188wwwwwwweeebmeeeeeebmeeekkkkcssssssssuuuuuuuupppppppapppppppaoooooooorrerrrrrtttttttt...cccccccaoooooooome mmmmm

CONTENTS
CONTENTS
Gastroenterology Today
4 EDITOR’S COMMENT
08 FEATURE Celiac disease related liver manifestations in
two case study patients
This issue edited by:
Aaron Bhakta
c/o Media Publishing Company
Greenoaks, Lockhill
Upper Sapey, Worcester, WR6 6XR
12 FEATURE Fatigue in patients with inflammatory bowel
disease—strongly influenced by depression
and not identifiable through laboratory testing:
a cross-sectional survey study
23 NEWS
27 COMPANY NEWS
ADVERTISING & CIRCULATION:
Media Publishing Company
Greenoaks, Lockhill
Upper Sapey, Worcester, WR6 6XR
Tel: 01886 853715
E: info@mediapublishingcompany.com
www.ambulanceukonline.com
PUBLISHED DATES:
March, June, September and December.
COPYRIGHT:
Media Publishing Company
Greenoaks
Lockhill
Upper Sapey, Worcester, WR6 6XR
COVER STORY
With over 30 steps to sufficient manual cleaning and reprocessing of reusable
Biopsy, Air/Water, and Suction Valves, the DEFENDO range of sterile single use
valves from STERIS UK, eliminates these steps.
PUBLISHERS STATEMENT:
The views and opinions expressed in
this issue are not necessarily those of
the Publisher, the Editors or Media
Publishing Company
Next Issue Autumn 2023
DEFENDO Valves are high-performance, high-quality products that support
procedural control and efficiency. Our verification testing includes multiple tests
for force and suction to help create valves that don’t exhibit some of the common
issues with reusable and other single-use valves: clogging, sticking and loss of
insufflation. When you experience these issues during a procedure, the result
can be a longer, more difficult procedure.
In the range there is the DEFENDO Single Use Y-OPSY Valve, for when the
GI endoscope does not have a dedicated auxiliary water port for irrigation.
This product allows the user to biopsy and irrigate simultaneously through the
working channel.
The newest addition to the DEFENDO range is the DEFENDO Single Use
Cleaning Adapter for OLYMPUS ® endoscopes, used to flush the air/water
channel after the procedure as a first step in the manual cleaning process.
This can help prevent biofilm formation and is seen as one of the most
important steps in cleaning and disinfecting an endoscope.
Available in kits that include, Air/Water, Suction and Biopsy Valves, the DEFENDO
range is compatible with Olympus, Pentax and Fujinon endoscopes. For more
information and/or a free sample please contact your STERIS UK Endoscopy
representative.
Designed in the UK by TGDH
GASTROENTEROLOGY TODAY – AUTUMN 2023
3

EDITOR’S COMMENT
EDITOR’S COMMENT
Looking beyond the typical.
“Whilst medical
conditions
and diseases
commonly
present with
classical
symptoms
there are also a
host of atypical
presentations
that one must
be aware and
mindful of.”
The differential diagnosis is one of the cornerstones of the medical profession and directs our patient
assessment from the very beginning. From medical students to senior clinicians, it is an everyday part
of clinical practice. Whilst medical conditions and diseases commonly present with classical symptoms,
there are also a host of atypical presentations that one must be aware and mindful of. When the diagnosis
is not forthcoming, we must look beyond the typical.
In this edition of Gastroenterology Today we present two feature articles. The first highlighting the liver
manifestations of coeliac disease and the importance of exploring the possibility of coeliac disease as
a diagnosis in patients with elevated liver enzymes of unknown aetiology. In the second feature, the authors
encourage clinicians to look beyond disease activity and anaemia in inflammatory bowel disease patients
presenting with fatigue, with the recommendation that these patients should be screened for possible
sub-clinical depression.
Aaron Bhakta
GASTROENTEROLOGY TODAY – AUTUMN 2023
4

TRIAGE GASTROSCOPY
REFERRALS WITH
GastroPanel® Quick Test
GastroPanel® is a simple and effective noninvasive
test to identify atrophic gastritis
and Helicobacter pylori (H. pylori) prior to
endoscopy.
Atrophic gastritis – a chronic condition of the gastric
mucosa, is considered to be the greatest independent
risk factor for developing gastric cancer and guidelines
recommend that individuals with extensive gastric
atrophy undergo regular endoscopic surveillance
to closely monitor their disease. Early detection of
individuals with a significant risk of developing gastric
cancer is the key to effective patient management,
helping to reduce unnecessary referrals, and improving
survival rates through earlier diagnoses.
GastroPanel helps select cases for
gastroscopy.
GastroPanel is a simple, effective and low cost blood
test that, through extensive validation, has consistently
proven to be effective in the determination of chronic
atrophic gastritis non-invasively. When GastroPanel
is positive, it helps direct appropriate and effective
treatment plans, including, enhanced image endoscopy,
eradication therapy, and surveillance.
GastroPanel measures three stomach biomarkers
from a finger-prick or venous blood sample, enabling
a thorough and objective investigation of the whole
gastric mucosa, non-invasively, giving clinicians more
confidence in their diagnoses and referrals.
GastroPanel measures concentrations of Pepsinogen I, Pepsinogen II,
Gastrin-17 and H. pylori IgG and produces a comprehensive report.
When endoscopy resources and capacity are
stretched.
This patient-friendly blood test can help transform
the referral pathway for upper GI investigations by
identifying those who need enhanced endoscopy
with biopsies. Implementing GastroPanel could help
to relieve the burden on overstretched endoscopy
services, streamline referrals, and reduce costs.
Scan to find out more or visit www.biohithealthcare.co.uk/gastropanel
BIOHIT HealthCare Ltd
Pioneer House, Pioneer Business Park, North Road,
Ellesmere Port, Cheshire, United Kingdom CH65 1AD
Tel. +44 151 550 4 550
info@biohithealthcare.co.uk
www.biohithealthcare.co.uk

Advertorial feature
What is the ideal treatment strategy for mild to moderate ulcerative
colitis: early treatment escalation or mesalazine optimisation?
Dr Anups de Silva
Consultant Gastroenterologist
and IBD Lead Clinician
Norfolk and Norwich University
Hospitals NHS Foundation Trust
With the advent of novel biologics and small molecules, and the increasing
availability of advanced diagnostic and management tools, the aspirations
for patients with ulcerative colitis (UC) are higher than ever. As such,
the International Organization for the Study of Inflammatory Bowel Disease
have updated their short- and long-term treatment targets for patients with
inflammatory bowel disease (IBD): 1
• Systemic response
• Symptomatic remission and normalisation of C-reactive protein
• Decrease in calprotectin to an acceptable range; normal growth in children
• Endoscopic healing; normalised quality of life and absence of disability
However, the role and timing of treatment escalation to achieve these goals is a
key area of debate. 2 Should we utilise these newer therapies as soon as patients
are eligible for them, or should we ensure that first-line established therapies,
such as mesalazine, have been fully optimised before treatment escalation?
Treatment strategies should be tailored to patients’
disease course
Whilst treatment must be tailored to the severity of patients’ disease, it is likely
to change over time. 2–4
A 20-year, prospective, population-based study found that 69% of patients
(n=340) had a disease course characterised by initially highly-active disease
followed by long-term remission or instances of mild intestinal symptoms. 4
Therefore, many patients may achieve good outcomes without the need for
early intervention with biologics. 4
The most common long-term disease course in patients with UC 4
Initially highly-active disease
followed by remission or mild 69%
intestinal symptoms
0 years 20 years
Adapted from Monstad et al. 2021. 4
Early anti-TNF use does not reduce hospitalisation and
surgery rates
In a retrospective study in patients with UC (n=318), early anti-tumour necrosis
factor (TNF) use (≤2 years after diagnosis) had no effect on hospitalisation and
surgery rates compared with anti-TNF use >2 years after diagnosis. 5
Disease activity
In addition to the lack of evidence supporting general early anti-TNF use in UC,
several challenges must also be considered when determining the optimal
treatment strategy:
1
2
3
A Cochrane review examining the adverse effects of biologics concluded
that they were associated with statistically significantly higher rates of
serious infection, tuberculosis reactivation, total adverse events (AEs) and
withdrawal due to AEs compared with control treatment. 6 A separate
Cochrane review into the use of mesalazine for the maintenance of
remission of UC found little or no difference between mesalazine and
placebo in commonly reported AEs. These included flatulence, abdominal
pain, nausea, diarrhoea, headache and dyspepsia 7
Early use may limit the effectiveness of treatment, as previous anti-TNF
use is associated with a heightened probability of treatment failure and loss
of response with subsequent anti-TNF therapy 8
Anti-TNF therapies are vastly more expensive than standard first-line
treatments such as mesalazine. 9 Even in the age of biosimilars, a single
dose of an anti-TNF can cost more than a whole year’s treatment
with mesalazine 9
Mesalazine optimisation remains the recommended
treatment strategy
The British Society of Gastroenterology recommend optimising the use of
first-line mesalazine treatment in patients with mild to moderate UC before
escalating to other therapies by: 3
• Increasing the dose up to 4–4.8g/day for the induction of remission
• Combining oral and rectal mesalazine (sometimes referred to as ‘top and tail
treatment’) for patients with an incomplete response
• Tailoring the choice of formulation to take into account patients’ preferences,
likely adherence and cost
These strategies can have a profound effect on the outcomes that can be
achieved with mesalazine. 10–13
Dr de Silva’s case study: mesalazine dose optimisation to
control a flare
Patient characteristics:
• 37-year-old male
• 2-year history of left-sided UC
• Treated with Octasa ® 2.4g/day taken once-daily
Presenting complaint:
• For 3 weeks he had been experiencing an increased frequency of
looser-consistency bowel movements (4 times per day and once at night)
with increased urgency, tenesmus and blood on most occasions
• Admitted to periods of non-compliance due to a heavy work schedule and
personal stresses
Investigations:
• Stool samples were sent for analysis with enteric pathogen polymerase chain
reaction (PCR) and Clostridioides difficile assay. Both were negative
• Faecal calprotectin was 1,424µg/g
• A flexible sigmoidoscopy revealed a Mayo Clinic Score of 2 and colitis
extending to the descending colon, with solid stool beyond this
Solution:
• His treatment was optimised by:
– Increasing the dose of Octasa ® to 4.8g/day, taken in 2 divided doses
– Starting treatment with a 1g mesalazine liquid enema at night, along with
an Octasa ® 1g suppository 12 hours apart from the enema
• During reassessment 10 days later, his bowel movement frequency had
reverted back to his normal habit of twice daily with a more solid stool

Mesalazine optimisation can increase response rates vs
standard dosing
In a randomised, multicentre induction trial with an open-label extension,
patients with moderately active UC and moderate/severe mucosal inflammation
initially received Octasa ® 3.2g/day for 8 weeks (n=817). 10 At week 8, patients
had their doses adjusted depending on their response to treatment, with those
who did not respond having their dose increased to 4.8g/day. 10
Response rate after increasing the dose of Octasa ® in patients with
moderate UC who did not respond to initial treamtent 10
Non-responders to
Octasa ® 3.2g/day at
week 8 (n=243)
Adapted from D’Haens et al. 2017. 10
Dose increase to
4.8g/day for
8 weeks (n=243)
75.3% achieved a response
with Octasa ® optimisation
(n=183/243)
Mesalazine optimisation can allow more patients to achieve
mucosal healing vs standard dosing
A post-hoc analysis of two prospective 6-week, double-blind, randomised studies
compared mucosal healing rates (defined as a Mayo endoscopy subscore of 0 or 1)
in patients with moderate UC who received 2.4g/day vs 4.8g/day oral mesalazine. 11
Of those patients treated with 4.8g/day, 80% achieved mucosal healing vs only
68% treated with 2.4g/day (n=322; p=0.012). Furthermore, mucosal healing
was found to be well correlated with clinical response and improvement in
patient-reported quality of life. 11
Mesalazine optimisation can reduce treatment costs vs
standard treatment
Modelled data from meta-analyses were used to compare mesalazine dose
optimisation (using the maximum dose, and combined oral and rectal therapy
before treatment escalation) with standard treatment in 10,000 patients with
mild to moderate UC. 12 It found mesalazine dose optimisation:
• Increased the initial remission rate from 47% to 66%
(n=4,725 vs n=6,565) 12
• Potentially avoided AEs associated with other
treatment classes, including psychological,
gastrointestinal, dermatological and haematological
AEs, infections and injection/infusion-related
reactions 12
Despite greater initial acquisition costs of increased mesalazine doses, the
substantial improvements in patient outcomes associated with mesalazine dose
optimisation resulted in net annual savings of £272 per patient. 12 With over
200,000 people living with mild to moderate UC in the UK, it has the potential
to save the NHS over £54 million per year. 12,14,15
Mesalazine optimisation can help meet patient preferences
Up to 3 in 5 patients have been found to be non-adherent to mesalazine in
observational studies. 16–19 However, prescribing mesalazines according to
patients’ preferences may help to improve this and reduce their risk of
relapse. 13,19 Patients should be prescribed a mesalazine that gives them the
number of tablets per administration, number of administrations per day and
treatment appearance that they prefer. 13
Mesalazine optimisation is the clear choice for mild to
moderate UC
Mesalazine optimisation should be employed before early treatment escalation
due to the available evidence:
• The majority of patients’ disease courses do not warrant early anti-TNF use 4,5
• Early anti-TNF use can pose several challenges, including reduced
effectiveness when anti-TNFs are used subsequently and high costs 8,9
• Mesalazine optimisation can increase rates of response and mucosal
healing, meet patients’ preferences and limit treatment costs vs standard
dosing and treatment 10–13
References: 1. Turner D et al. Gastroenterology 2021; 160(5): 1570–1583. 2. Raine T et al. J Crohns Colitis 2022; 16(1): 2–17. 3. Lamb CA
et al. Gut 2019; 68(Suppl 3): s1–s106. 4. Monstad IL et al. J Crohns Colitis 2021; 15(6): 969–979. 5. Targownik LE et al. Clin Gastroenterol
Hepatol 2022; 20(11): 2607–2618.e14. 6. Singh JA et al. Cochrane Database Syst Rev 2011; 2: CD008794. 7. Murray A et al. Cochrane
Database Syst Rev 2020; 8: CD000544. 8. Atreya R et al. Front Med (Lausanne) 2020; 7: 517. 9. BNF. Accessed online, August 2023.
10. D’Haens GR et al. Aliment Pharmacol Ther 2017; 46(3): 292–302. 11. Lichtenstein GR et al. Aliment Pharmacol Ther 2011; 33(6):
672–678. 12. Louis E et al. BMJ Open Gastroenterol 2022; 9(1): e000853. 13. MacKenzie-Smith L et al. Inflamm Intest Dis 2018; 3(1):
43–51. 14. Crohn’s and Colitis UK. Epidemiology Summary: Incidence and Prevalence of IBD in the United Kingdom. Available at: https://
crohnsandcolitis.org.uk/media/4e5ccomz/epidemiology-summary-final.pdf [accessed August 2023]. 15. Schreiber S et al. J Crohns Colitis
2013; 7(6): 497–509. 16. Testa A et al. Patient Prefer Adherence 2017; 11: 297–303. 17. Kane SV et al. Am J Gastroenterol 2001; 96(10):
2929–2933. 18. Shale MJ et al. Aliment Pharmacol Ther 2003; 18(2): 191–198. 19. Kane SV et al. Am J Med 2003; 114(1): 39–43.
OCTASA 1g Suppositories (mesalazine) - Prescribing Information
Presentation: Suppository containing 1g mesalazine. Indications: Treatment of acute mild to moderate ulcerative proctitis. Maintenance of
remission of ulcerative proctitis Dosage and administration: Adults and older people: Acute treatment - one Octasa 1 g Suppository once
daily (equivalent to 1 g mesalazine daily) inserted into the rectum. Maintenance treatment - one Octasa 1 g Suppository once daily (equivalent
to 1 g mesalazine daily) inserted into the rectum. Children: Limited experience and data for use in children. Method of administration: for
rectal use, preferably at bedtime. Duration of use to be determined by the physician. Contra-indications: Hypersensitivity to salicylates
or any of the excipients, severe impairment of hepatic or renal function. Warnings and Precautions: Blood tests and urinary status (dip
sticks) should be determined prior to and during treatment, at discretion of treating physician. Caution in patients with impaired hepatic
function. Do not use in patients with impaired renal function. Consider renal toxicity if renal function deteriorates during treatment. Cases
of nephrolithiasis have been reported with mesalazine treatment. Ensure adequate fluid intake during treatment. Monitor patients with
pulmonary disease, in particular asthma, very carefully. Patients with a history of adverse drug reactions to sulphasalazine should be kept
under close medical surveillance on commencement of therapy, discontinue immediately if acute intolerance reactions occur (e.g. abdominal
cramps, acute abdominal pain, fever, severe headache and rash). Severe cutaneous adverse reactions (SCARS), including Drug reaction with
eosinophilia and systemic symptoms (DRESS), Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported.
Stop treatment immediately if signs and symptoms of severe skin reactions are seen. Mesalazine may produce red-brown urine discoloration
after contact with sodium hypochlorite bleach (e.g. in toilets cleaned with sodium hypochlorite contained in certain bleaches). Interactions:
No interaction studies have been performed. May increase the myelosuppressive effects of azathioprine, 6-mercaptopurine or thioguanine.
May decrease the anticoagulant activity of warfarin. Fertility, pregnancy and lactation: Only to be used during pregnancy and lactation
when the potential benefit outweighs the possible risk. No effects on fertility have been observed. Adverse reactions: Rare: Headache,
dizziness, myocarditis, pericarditis, abdominal pain, diarrhoea, flatulence, nausea, vomiting, constipation, photosensitivity, Very rare: Altered
blood counts (aplastic anaemia, agranulocytosis, pancytopenia, neutropenia, leukopenia, thrombocytopenia), peripheral neuropathy, allergic
and fibrotic lung reactions (including dyspnoea, cough, bronchospasm, alveolitis, pulmonary eosinophilia, lung infiltration, pneumonitis),
acute pancreatitis, impairment of renal function including acute and chronic interstitial nephritis and renal insufficiency, alopecia, myalgia,
arthraligia, hypersensitivity reactions (such as allergic exanthema, drug fever, lupus erythematosus syndrome, pancolitis), changes in liver
function parameters (increase in transaminases and parameters of cholestasis), hepatitis, cholestatic hepatitis, oligospermia (reversible). Not
known: Nephrolithiasis, Drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis.
Consult the Summary of Product Characteristics in relation to other adverse reactions. Marketing Authorisation Numbers, Package
Quantities and basic NHS price: PL36633/0011; packs of 10 suppositories (£9.87) and 30 suppositories (£29.62). Legal category:
POM. Marketing Authorisation Holder: Tillotts Pharma UK Ltd, The Larbourne Suite, The Stables, Wellingore Hall, Wellingore, Lincolnshire,
LN5 0HX, UK. Octasa is a trademark. © 2021 Tillotts Pharma UK Ltd. Further Information is available from the Marketing Authorisation Holder.
Date of preparation of PI: November 2022
Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk.
Adverse events should also be reported to Tillotts Pharma UK Ltd. (address as above) Tel: 01522 813500.
OCTASA 400mg, 800mg & 1600mg Modified Release Tablets (mesalazine) - Prescribing Information
Presentation: Modified Release tablets containing 400mg, 800mg or 1600mg mesalazine. Indications: All strengths: Ulcerative Colitis -
Treatment of mild to moderate acute exacerbations. Maintenance of remission. 400mg & 800mg only: Crohn’s ileocolitis - Maintenance of
remission. Dosage and administration: 400mg & 800mg tablets – Adults: Mild acute disease: 2.4g once daily or in divided doses, with
concomitant steroid therapy where indicated. Moderate acute disease: 2.4g – 4.8g daily. 2.4g may be taken once daily or in divided doses,
higher doses should be taken in divided doses. Maintenance therapy: 1.2g – 2.4g once daily or in divided doses. 1600mg tablets – Adults:
Acute exacerbations: up to 4.8g, once daily or in divided doses. Maintenance: 1600mg daily. Tablets must be swallowed whole. Elderly:
400mg & 800mg - normal adult dose may be used unless liver or renal function is severely impaired. 1600mg - no studies in elderly patients
have been conducted. Children: 400mg & 800mg - limited documentation of efficacy in children >6 years old. Dose to be determined
individually. Generally recommended that half the adult dose may be given to children up to a body weight of 40 kg; and the normal adult
dose to those above 40 kg. 1600mg – safety and efficacy not established in children. Contra-indications: Hypersensitivity to salicylates,
mesalazine or any of the excipients, severe impairment of hepatic or renal function (GFR less than 30 ml/min/1.73m 2 ). Warnings and
Precautions: Urinary status (dip sticks) should be determined prior to and during treatment, at discretion of treating physician. Caution
in patients with raised serum creatinine or proteinuria. Stop treatment immediately if renal impairment is evident. Cases of nephrolithiasis
have been reported with mesalazine treatment. Ensure adequate fluid intake during treatment. Severe cutaneous adverse reactions
(SCARS), including Drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson Syndrome (SJS) and toxic epidermal
necrolysis (TENS) have been reported. Stop treatment immediately if signs and symptoms of severe skin reactions are seen. Haematological
investigations are recommended prior to and during treatment, at discretion of treating physician. Stop treatment immediately if blood
dyscrasias are suspected or evident. Caution in patients with impaired hepatic function. Liver function should be determined prior to and
during treatment, at the discretion of the treating physician. Do not use in patients with previous mesalazine-induced cardiac hypersensitivity
and use caution in patients with previous myo- or pericarditis of allergic background. Monitor patients with pulmonary disease, in particular
asthma, very carefully. In patients with a history of adverse drug reactions to sulphasalazine, discontinue immediately if acute intolerance
reactions occur (e.g. abdominal cramps, acute abdominal pain, fever, severe headache and rash). Use with caution in patients with gastric
or duodenal ulcers. Intact 400mg & 800mg tablets in the stool may be largely empty shells. If this occurs repeatedly patients should consult
their physician. Use with caution in the elderly, subject to patients having normal or non-severely impaired renal and liver function. Patients
with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption, should not take
the 400mg or 800mg tablets. Mesalazine may produce red-brown urine discoloration after contact with sodium hypochlorite bleach (e.g.
in toilets cleaned with sodium hypochlorite contained in certain bleaches). Interactions: No interaction studies have been performed.
May decrease the anticoagulant activity of warfarin. Caution when used with known nephrotoxic agents such as NSAIDs, methotrexate
and azathioprine. May increase the myelosuppressive effects of azathioprine, 6-mercaptopurine or thioguanine. Monitoring of blood cell
counts is recommended if these are used concomitantly. Fertility, pregnancy and lactation: Only to be used during pregnancy and
lactation when the potential benefit outweighs the possible risk. No effects on fertility have been observed. Adverse reactions: Common:
dyspepsia, rash. Uncommon: eosinophilia (as part of an allergic reaction), paraesthesia, urticaria, pruritus, pyrexia, chest pain. Rare:
headache, dizziness, myocarditis, pericarditis, abdominal pain, diarrhoea, flatulence, nausea, vomiting, photosensitivity. Very rare: altered
blood counts (aplastic anemia, agranulocytosis, pancytopenia, neutropenia, leucopenia, thrombocytopenia), blood dyscrasia, hypersensitivity
reactions (such as allergic exanthema, drug fever, lupus erythematosus syndrome, pancolitis), peripheral neuropathy, allergic and fibrotic lung
reactions (including dyspnoea, cough, bronchospasm, alveolitis, pulmonary eosinophilia, lung infiltration, pneumonitis), interstitial pneumonia,
eosinophilic pneumonia, lung disorder, acute pancreatitis, changes in liver function parameters (increase in transaminases and cholestasis
parameters), hepatitis, cholestatic hepatitis, alopecia, myalgia, arthralgia, impairment of renal function including acute and chronic interstitial
nephritis and renal insufficiency, renal failure which may be reversible on withdrawal, nephrotic syndrome, oligospermia (reversible). Not
known: Drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson Syndrome, toxic epidermal necrolysis, pleurisy, lupuslike
syndrome with pericarditis and pleuropericarditis as prominent symptoms as well as rash and arthralgia, nephrolithiasis, intolerance
to mesalazine with C-reactive protein increased and/or exacerbation of symptoms of underlying disease, blood creatinine increased,
weight decreased, creatinine clearance decreased, amylase increased, red blood cell sedimentation rate increased, lipase increased, BUN
increased. Consult the Summary of Product Characteristics in relation to other adverse reactions. Marketing Authorisation Numbers,
Package Quantities and basic NHS price: 400mg - PL36633/0002; packs of 90 tablets (£19.50) and 120 tablets (£26.00). 800mg -
PL36633/0001; packs of 90 tablets (£40.38) and 180 tablets (£80.75). 1600mg – PL36633/0009; packs of 30 tablets (£30.08). Legal
category: POM. Marketing Authorisation Holder: Tillotts Pharma UK Ltd, The Larbourne Suite, The Stables, Wellingore Hall, Wellingore,
Lincolnshire, LN5 0HX, UK. Octasa is a trademark. © 2022 Tillotts Pharma UK Ltd. Further Information is available from the Marketing
Authorisation Holder. Date of preparation of PI: November 2022
Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk.
Adverse events should also be reported to Tillotts Pharma UK Ltd. (address as above) Tel: 01522 813500.
This advertorial has been funded and initiated by Tillotts Pharma UK (TPUK). The content in this
advertorial has been driven by Dr de Silva and written by TPUK. Dr de Silva has reviewed the
content, and TPUK have ensured technical accuracy and compliance with appropriate regulations
and legislation.
Date of preparation: August 2023. PU-01292.

FEATURE
CELIAC DISEASE RELATED LIVER
MANIFESTATIONS IN TWO CASE
STUDY PATIENTS
RESEARCH
Key words: celiac, gluten free, dietitian, liver, elevated liver enzymes
Kathleen Eustace, MPH, RDN, LD, CNSC Corresponding Author
UT Southwestern Medical Center Department of Clinical Nutrition
Associate professor
6011 Harry Hines Blvd. Dallas, TX 75390-8877
214-648-1520
kathleen.eustace@utsouthwestern.edu
Alicia Gilmore, MS, RD, CSO, LD
UT Southwestern Medical Center Department of Clinical Nutrition
Associate professor
6011 Harry Hines Blvd. Dallas, TX 75390-8877
214-648-1520
alicia.gilmore@utsouthwestern.edu
Funding/ Support Disclosure: No funding was received for this article.
Conflict of Interest: Neither author has any conflict of interests to report.
Abstract
from exposure of dietary gluten. CD primarily affects the small intestine
and resolves with a gluten free diet (1). Classic presentation includes
diarrhea, gassiness, abdominal pain, iron deficiency anemia, and weight
loss. Organs, connective tissues, skin, joints, and the nervous system
can also be affected by the systemic inflammatory response to gluten
(2). Non-gastrointestinal manifestations include joint pain, dermatitis
herpetiformis, low bone mineral density, and liver disease which
manifests initially as elevated alanine and aspartate aminotransferase
(ALT and AST, respectively) (1, 3). Diagnostic evaluation of CD should be
completed with any range of symptoms without an alternative etiology,
not just with presentation of historically associated symptoms.
Elevated transaminase levels, or liver function tests (LFTs), can be
a primary, and often overlooked, symptom of CD in the absence of
additional symptoms (3, 4, 5, 6, 7, 8). Elevated LFT levels are reported
in 40% of adults and 60% of children with CD (8). Undiagnosed celiac
disease accounts for 9% of patients with transaminase elevations of
unknown etiology (9, 10). The cause of CD related liver involvement
is unclear, but literature suggests a possible mechanism is increased
intestinal permeability of CD, allowing toxins and inflammatory mediators
to reach the liver via the lymphatic system (11). Dietary therapy will
reverse CD related liver disease, potentially preventing progression to
overt liver failure (3, 11).
GASTROENTEROLOGY TODAY – AUTUMN 2023
Celiac sprue or Celiac disease (CD) is an autoimmune disease that
resolves with the removal of gluten from the diet. Traditionally CD
presents with weight loss, iron deficiency anemia, and gastrointestinal
symptoms such as gas, pain, and/or bloating. However, there is an
increasing prevalence of novel presentations of CD, such as dermatitis
herpetiformis, joint pain, and elevated transaminase levels. Elevated
transaminase levels are cited in literature as the only presentation of
celiac disease. Progression to liver disease and even liver failure can
occur if not addressed in early stages with the initiation of a gluten
free diet. Physician awareness of CD related liver involvement is of the
upmost importance for both diagnosis and dietary nonadherence.
Registered Dietitian Nutritionists (RDN) specializing in gluten free diets
are poised to provide in-depth diet initiation and adherence support.
RDNs can also perform the important task of educating on long term
adherence to prevent poor outcomes including liver disease. This case
study reviews two patients presenting with CD related transaminase
elevations without other clinical manifestations. The purpose of this
review is to highlight the importance of recognizing CD as an etiology
for elevated transaminase levels and the valuable role the RDN plays
in supporting dietary treatment to prevent and treat CD related liver
disease.
Background
Celiac sprue or Celiac disease (CD) is an autoimmune disorder resulting
Strict adherence to the prescribed gluten free diet is paramount to the
prevention of CD related liver disease. Nonadherence occurs in 25-
40% of CD patients due to intentional and unintentional consumption
of gluten resulting in persistence and/or recurrence of symptoms (12,
13). Amelioration of symptoms that interfere with daily life supports
compliance with the required diet. However, if symptoms are silent, they
can be ignored by patients inclined to noncompliance with the gluten
free diet. CD related LFT abnormalities without other conspicuous
symptoms will often go unnoticed by the patient (3, 14, 15). Registered
dietitian nutritionist (RDN) educating on prescribed dietary therapy
will need to emphasize the risk of symptom occurrence with dietary
noncompliance at initial and follow up visits. In this article, we report
two cases of CD presenting solely with elevated LFTs. The first where
the diagnosis was incidental to elevated levels, while the second
demonstrates dietary non-compliance resulting in liver disease in the
absence of other symptoms. All HIPAA (Health Information Patient
Accountability Act) guidelines and privacy rules were followed with
respect to using or accessing PHI in the review of the cases.
Case Study 1
A 30-year-old Caucasian woman was referred to the Gastroenterology
Clinic for elevated transaminase levels found incidentally during a
pre-operative evaluation. Past medical history included thyroid cancer
with full thyroidectomy, type I diabetes, asthma, and childhood anemia.
8

FEATURE
A liver ultrasound was normal including size, texture, and echogenicity.
Immunoglobulin G and Immunoglobulin A antibodies were assessed
with both levels within the normal range. The patient denied weight
loss or gastrointestinal symptoms including diarrhea, gas, or post
prandial abdominal pain. Etiologies of nonalcoholic fatty liver disease
and hepatic glycogenosis (due to the patient’s diagnosis of type 1
Diabetes Mellitus) were suspected. The patient was referred for an
esophagogastroduodenoscopy (EGD) with biopsy. EGD was notable
for erythematous mucosa in the antrum as well as flattened mucosa
in the duodenum. Biopsies confirmed the diagnosis along with an
elevated serum tissue transglutaminase. The patient received the CD
diagnosis and a referral to an RDN. The completed nutrition assessment
included both anthropometrics and 24-hour diet recall. There had been
no change in weight prior to the visit or with the diagnosis of CD. Blood
glucose concentrations were stable, with the patient using a Medtronic
pump and Dexcom monitor. Transaminase levels are noted in Table 1.
The patient admitted difficulty identifying hidden sources of gluten, as
well as concerns for both eating out safely and the potential for nutrient
deficiencies (iron, b vitamins). Formal gluten free diet education was
provided and individualized to the patients’ need. Supplementation of
a gluten free multivitamin and mineral supplement was recommended.
Lifelong dietary adherence was emphasized with the patient as a
requirement for long term positive outcomes. Dietary compliance with a
gluten free diet was measured by normalization of LFTs and a reduction
in tissue transglutaminase level at 5 months and 11 months respectively
after initial diagnosis.
Subsequent scheduled follow ups were cancelled by the patient,
and she was lost to follow up.
Case Study 2
A 49-year-old Caucasian female with a history of CD presented for
dietary re-education due to long-term gluten free diet non-adherence.
The patient presented nine years prior with abdominal pain and irregular
stool output including diarrhea and constipation. Serologies from an
outside facility were consistent with a diagnosis of CD and an EGD with
small bowel biopsy supported the diagnosis of CD. The patient received
formal education on a gluten free diet at initial diagnosis. The patient
reported good dietary adherence initially but gradually reintroduced
gluten without recurrence of symptoms. Mildly elevated transaminase
levels were noted four years after diagnosis but normalized until eight
years after diagnoses (Table 2). No alternative etiology for her elevated
LFTs was determined leading to the conclusion that her underlying
CD and subsequent dietary noncompliance was the cause of her
transaminase elevations. Subsequent serology revealed an elevated
serum tissue transglutaminase. The patient reinitiated a gluten free diet
and a formal RDN referral was placed. A nutrition assessment revealed
normal weight status, supplementation of iron, calcium, and vitamin
D, as well as recent initiation of gluten free diet. A diet recall revealed
gluten ingestion via flour-based cake, bread, and foods with a high risk
of cross contamination including specialty coffees, hot cereals, and
foods cooked with unknown seasonings. Individualized formal education
was provided to reinforce adherence to a gluten free diet. The RDN
emphasized strict diet adherence to prevent further complications.
Liver transaminase levels returned to normal limits six weeks after
reinitiating a strict gluten free diet (Table 2). Follow up with the RDN
was scheduled on an as needed basis.
Discussion
Fifteen to fifty-five percent of CD patients experience elevated
transaminase levels and/or changes in liver morphology (1, 2, 3, 4, 5, 6,
7, 8, 9, 10). Non-adherence to a gluten free diet can lead to progressive
liver disease and advancement to cirrhosis and liver failure in some
individuals (3). Adherence to a gluten free diet is critical to prevent CD
related liver disease progression. Both physicians and RDNs should
recognize nonstandard presentations of CD. Case 1 highlights the
importance of recognizing and diagnosing CD in the setting of isolated
transaminase elevations. An inclusive work up with a liver panel and tissue
Table 1 Liver Chemistry Results Before and After Diagnosis of Celiac Disease
Baseline 2 months 5 months 9 months 11 months
Alk Phos (U/mL) 109 116 117 92
Alpha 1 Antitrypsin 200
ALT (U/mL) 59 56 29 23
AST (U/mL) 38 37 20 22
Tissue transglutaminase AB, IGA, S (U/mL) ≥100.0 7
Table 2 Liver Chemistry Results After Diagnosis of Celiac Disease for Case 2
Post 4 years Post 7 years Post 8 years a
January April July October December
AST (U/L) 60 29 61 53 45 38 22
ALT (U/L) 68 24 41 37 52 52 29
TTG (U/mL) 15.9
GASTROENTEROLOGY TODAY – AUTUMN 2023
a
Labs were drawn throughout the year due to the initial findings of hypertransaminemia
9

FEATURE
transglutaminase collected prior to diagnosis should be repeated after
6-12 months of strict adherence to a gluten free diet (5). These tests act as
an indicator of dietary adherence and disease activity. As with the patient
in Case 1, transaminase levels are expected to return to normal on a strict
gluten free diet.
Case 2 highlights how CD patients non-compliant with dietary restrictions
can expect morphological and/or systemic changes. Elevated liver
transaminase levels were not part of her initial presentation, but an
unexpected consequence of gluten reintroduction. Gradual introduction
of gluten overtime without overt symptoms recurrence led to increased
dietary noncompliance, as reported by the patient. Dietary education
must emphasize adherence even after initial symptom resolution due to
the underlying pathological changes that can occur with gluten ingestion
in patients with CD. Physicians and RDNs should reinforce the importance
of dietary adherence to prevent long term consequences of untreated
CD. Emphasis should be placed on the risk associated with dietary nonadherence
even in the absence of obvious clinical symptoms such as
elevated plasma transaminase levels.
Restrictive diets such as the gluten free diet can present a challenge.
Education and reinforcement of a strict gluten free diet by an RDN can
prevent poor dietary adherence (16). The Nutrition Care Manual ® , a
nutrition intervention guide provided by the Academy of Nutrition and
Dietetics. recommends ‘if the potential exists for a nutrition diagnosis
to develop (i.e., dietary nonadherence), the registered dietitian should
establish an appropriate method and interval for follow up (17). This
guideline is designed to reinforce dietary adherence to prevent CD
manifestations of severe negative consequence including not only the
reviewed CD-related hepatic pathology reviewed here, but others such as
an increased risk of certain cancers (1, 7). Unfortunately, neither patient
was seen for follow up after initial diagnosis and consultation. Case 2 had
no follow up with an RDN over the 8 years from initial CD diagnosis until
liver complications developed. Likewise, case 1 failed to schedule a follow
up consultation. Physician appointments with CD patients should include
screening for dietary adherence with subsequent referral to RDNs as
needed to reinforce adherence to a strict gluten free diet.
gluten-free diet may reverse hepatic failure. Gastroenterology.
2002;122(4):881-8.
4. Korpimaki S, Kaukinen K, Collin P, Haapala AM, Holm P, Laurila K,
et al. Gluten-Sensitive Hypertransaminasemia in Celiac Disease:
An Infrequent and Often Subclinical Finding. American Journal of
Gastroenterology. 2011;106(9):1689-96.
5. Kamath PS. Clinical approach to the patient with abnormal liver
test results. Mayo Clin Proc. 1996;71(11):1089-94; quiz 94-5.
6. Rubio-Tapia A, Murray JA. The liver in celiac disease. Hepatology.
2007;46(5):1650-8.
7. Sainsbury A, Sanders DS, Ford AC. Meta-analysis: Coeliac
disease and hypertransaminasaemia. Aliment Pharmacol Ther.
2011;34(1):33-40.
8. Rubio-Tapia A, Abdulkarim AS, Wiesner RH, Moore SB,
Krause PK, Murray JA. Celiac disease autoantibodies in severe
autoimmune liver disease and the effect of liver transplantation.
Liver Int. 2008;28(4):467-76.
9. Volta U, De Franceschi L, Lari F, Molinaro N, Zoli M, Bianchi FB.
Coeliac disease hidden by cryptogenic hypertransaminasaemia.
Lancet. 1998;352(9121):26-9.
10. Bardella MT, Vecchi M, Conte D, Del Ninno E, Fraquelli M,
Pacchetti S, et al. Chronic unexplained hypertransaminasemia may
be caused by occult celiac disease. Hepatology. 1999;29(3):654-
7.
11. Villavicencio Kim J, Wu GY. Celiac Disease and Elevated Liver
Enzymes: A Review. J Clin Transl Hepatol. 2021;9(1):116-24.
12. Gladys K, Dardzinska J, Guzek M, Adrych K, Malgorzewicz
S. Celiac Dietary Adherence Test and Standardized Dietician
Evaluation in Assessment of Adherence to a Gluten-Free Diet in
Patients with Celiac Disease. Nutrients. 2020;12(8).
13. Hall NJ, Rubin GP, Charnock A. Intentional and inadvertent nonadherence
in adult coeliac disease. A cross-sectional survey.
Appetite. 2013;68:56-62.
14. Hagander B, Berg NO, Brandt L, Norden A, Sjolund K,
Stenstam M. Hepatic injury in adult coeliac disease. Lancet.
1977;2(8032):270-2.
15. Ludvigsson JF, Elfstrom P, Broome U, Ekbom A, Montgomery
SM. Celiac disease and risk of liver disease: a general populationbased
study. Clin Gastroenterol Hepatol. 2007;5(1):63- 9 e1.
16. Nealis C LC, Hollenbeck C. The Recovery Experience of Celiac
Patients Following a Gluten-Free Diet: An ExploratoryStudy.
Journal of the Academy of Nutrition and Dietetics. 2016;116;
9:A96.
17. Dietetics AoNa. Celiac Disease. Nutrition Therapy Efficacy 2021
[Available from: https://www.nutritioncaremanual.org/topic.
cfm?ncm_category_id=1&lv1=5522&lv2=22684&lv3=269416&n
cm_toc_id=269416&ncm_heading=Nutrition%20Care.
Conclusion
GASTROENTEROLOGY TODAY – AUTUMN 2023
Currently, a consensus regarding evaluation of CD in patients with nonclassical
symptom presentations does not exist; however, exploration
of CD as a diagnosis is recommended in those presenting with elevated
transaminase levels of unknown etiology (1). Once diagnosed, education
on the risk dietary nonadherence should be routinely emphasized by both
the treating physicians and RDNs. Elevated transaminase and progressive
liver disease is a specific long-term consequence of CD that can easily
be overlooked as both a symptom of the disease and a sign of nonadherence
to a gluten free diet.
References
1. Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA. ACG
clinical guidelines: diagnosis and management of celiac disease.
Am J Gastroenterol. 2013;108(5):656-76.
2. Tovoli F, De Giorgio R, Caio G, Grasso V, Frisoni C, Serra M, et al.
Autoimmune Hepatitis and Celiac Disease: Case Report Showing
an Entero-Hepatic Link. Case Rep Gastroenterol. 2010;4(3):469-
75.
3. Kaukinen K, Halme L, Collin P, Farkkila M, Maki M, Vehmanen
P, et al. Celiac disease in patients with severe liver disease:
10

Optimising
maintenance therapy
for ulcerative colitis:
Real
choices
When mesalazine doesn’t seem to be working, stepping
up to immunosuppressants isn’t the only option
Together we know more.
Together we do more.
Real
solution
Salofalk Granules are easy to take, they have a
pleasant vanilla flavour, and they’re a proven way to
help patients get the most from their mesalazine 1-3
Optimising therapy with once-daily Salofalk Granules in patients
who were inadequately maintained on previous mesalazine resulted in: 2
69% 45% 50%
fewer
days
off work
fewer
GP visits
due to UC
fewer
steroid
courses used
Mesalazine, the Dr Falk way
Prescribing Information Information (refer (refer to to full full SPC SPC before before prescribing): prescribing):
Salofalk
Presentation:
gastro-resistant
Salofalk 250mg
prolonged-release
gastro-resistant tablets:
granules
gastro-resistant tablet
containing 250mg mesalazine. Salofalk 500mg and 1g gastro-resistant tablet
Presentation: (UK ONLY) containing Stick-formed 500mg or and round, 1g mesalazine greyish white respectively. gastro-resistant Salofalk
prolonged-release 500mg/1000mg/1500mg/3000mg granules in sachets prolonged-release containing granules: 500mg, prolongedrelease
or granules 3g mesalazine containing per 500mg,1000mg, sachet. Indications: 1500mg or Treatment 3000mg mesalazine of acute
1000mg,
1.5g
episodes per sachet. and Indications: the maintenance Salofalk 250mg of remission tablets (UK): of ulcerative treatment colitis. and
Dosage: maintenance Adults: of remission Once daily of 1 mild/moderate sachet of 3g granules, ulcerative 1 colitis. or 2 sachets Salofalk of
1.5g 250mg granules tablets or (Ireland): 3 sachets as of an 1000mg anti-inflammatory 500mg granules in the management (equivalent of to
1.5
ulcerative
– 3.0g
colitis
mesalazine
and in
daily)
the treatment
preferably
of Crohn’s
taken in
disease.
the morning,
Salofalk
according
500mg
tablets (UK): treatment and maintenance of remission of ulcerative colitis.
to
Salofalk
individual
1g tablets
clinical
(UK):
requirement.
treatment
May
of acute
be taken
episodes
in three
of mild/moderate
divided doses
(1 ulcerative sachet colitis. of 500mg Salofalk granules granules: three treatment times daily of acute or 1 sachet episodes of 1000mg and the
granules maintenance three of remission times daily) of mild if more to moderate convenient. ulcerative Maintenance: colitis. Dosage: 0.5g
mesalazine Salofalk 250mg three tablets times - Adults daily and elderly: (morning, acute treatment midday 6 -12 and tablets evening) daily
corresponding 3 divided doses. to Maintenance a total dose treatment of 1.5g mesalazine 6 tablets daily per in day. 3 divided For patients doses.
known Salofalk to 500mg be at tablets increased (UK only): risk for 1 relapse or 2 tablets for 3 medical times daily. reasons Maintenance: or due to
difficulties 1 tablet 3 times to adhere daily. Salofalk to three 1g tablets daily doses, (UK only): give 1 tablet 3.0g mesalazine three times daily. as a
Salofalk granules – adults: acute treatment – once daily 1 sachet of 3g
single daily dose, preferably in the morning. Children: There is only
granules, 1 or 2 sachets of Salofalk 1.5g granules, 3 sachets of 500mg
granules limited documentation or 3 sachets of for 1000mg an effect granules in children (equivalent (age to 6-18 1.5 – years). 3.0g
mesalazine Children 6 daily), years preferably of age and taken older: in the Active morning. disease: Alternatively, To be the determined dose can
be individually, taken divided starting three with doses. 30-50mg/kg/day Maintenance treatment once daily – 1 preferably sachet of 500mg in the
granules morning 3 or times in divided daily (1.5g doses. mesalazine Maximum daily). dose: Where 75mg/kg/day. needed, 3.0g per The day total in
a dose single should morning not dose exceed may be taken. the maximum Method of administration: adult dose. Maintenance oral. Tablets
treatment: - taken whole To without be determined chewing, with individually, liquid, one starting hour before with meals. 15-30mg/kg/day Granules
in
- taken
divided
on the
doses.
tongue
The
and
total
swallowed,
dose should
without
not
chewing,
exceed
with
the
plenty
recommended
of liquid.
Duration of treatment is usually 8 weeks. To be determined by physician.
adult
Children
dose.
(all formulations):
It is generally
there
recommended
is only limited
that
documentation
half the adult
for
dose
an effect
may
be in children given to (age children 6-18 years). up to a Children body weight 6 years of and 40kg; older: and active the normal disease – adult on
dose individual to those basis starting above with 40kg. 30-50mg/kg/day Method of administration: either once daily Taken (granules) on the or
tongue in divided and doses swallowed, (tablets and without granules). chewing, Maximum with 75mg/kg/day. plenty of liquid. Total Contraindications:
should not exceed Hypersensitivity recommended to adult salicylates dose. Maintenance or any of the - on excipients. individual
dose
Severe basis starting impairment with 15-30mg/kg/day of renal or hepatic in divided function. doses. Warnings/Precautions:
Total dose should not
Blood
exceed
tests
recommended
and urinary
adult
status
dose.
(dip
Generally
sticks) should
recommended
be determined
that half
prior
the
adult dose may be given to children up to a body weight of 40kg and the
to
normal
and
adult
during
dose
treatment.
to those above
Caution
40kg.
is
Contra-indications:
recommended in
Hypersensitivity
patients with
impaired to salicylates hepatic or any of function. the excipients. Should Severe not impairment be used of in renal patients or hepatic with
impaired function. Warnings/Precautions: renal function. Mesalazine-induced Blood tests and urinary renal toxicity status (dip should sticks) be
considered should be determined if renal function prior deteriorates to and during during treatment. treatment. Caution Cases is of
recommended in patients with impaired hepatic function. Should not be
used in patients with impaired renal function. Mesalazine-induced renal
toxicity should be considered if renal function deteriorates during treatment
- stop treatment immediately in such cases. Cases of nephrolithiasis
reported; ensure good hydration. Serious blood dyscrasias have been
reported very rarely with mesalazine. Hematological investigations should
be performed if patients suffer from unexplained haemorrhages, bruises,
purpura, anaemia, fever or pharyngolaryngeal pain. Salofalk should be
nephrolithiasis
discontinued in case
reported;
of suspected
ensure
or confirmed
good hydration.
blood dyscrasia.
Patients
Cardiac
with
hypersensitivity reactions (myocarditis, and pericarditis) induced by
pulmonary
mesalazine have
disease,
been rarely
in
reported.
particular
Salofalk
asthma,
should
should
then be
be
discontinued
carefully
monitored. immediately. Patients with with pulmonary a history disease, of adverse in particular drug asthma, reactions should to
preparations be carefully monitored. containing Severe sulphasalazine cutaneous should adverse be reactions kept under (SCARs), close
medical including surveillance. drug reaction with If acute eosinophilia intolerance and systemic reactions symptoms e.g., abdominal (DRESS),
cramps, Stevens-Johnson acute abdominal syndrome pain, (SJS) and fever, toxic severe epidermal headache necrolysis and (TEN), rash, occur, have
stop been reported. treatment Discontinue immediately. treatment Severe at the cutaneous first appearance adverse of signs reactions and
(SCARs), symptoms of including severe skin Stevens-Johnson reactions, such as skin syndrome rash, mucosal (SJS) lesions, and or toxic any
other sign of hypersensitivity. Patients with a history of adverse drug reactions
epidermal necrolysis (TEN), have been reported. Discontinue
to preparations containing sulphasalazine should be kept under close
treatment medical surveillance. at the first If appearance acute intolerance of signs reactions and symptoms e.g., abdominal of severe cramps, skin
reactions, acute abdominal such pain, as skin fever, rash, severe mucosal headache lesions, and rash or occur, any stop other treatment sign of
hypersensitivity. immediately. Tablets Salofalk may granules be excreted contain undissolved aspartame, in patients a source with the of
phenylalanine ileocecal valve removed. that may Salofalk be harmful granules: for patients contain with aspartame, phenylketonuria. a source of
Salofalk phenylalanine. granules May contain be harmful sucrose: to patients 0.02mg, with phenylketonuria. 0.04mg, 0.06mg Granules and
0.12mg also contain (500mg/1g/1.5g sucrose: 0.04mg, and 0.08mg, 3g granules 0.12mg, respectively). 0.24mg (500mg/1g/1.5g
Interactions:
Specific
and 3g granules
interaction
respectively).
studies have
Salofalk
not
tablets:
been performed.
For patients on
Lactulose
a sodiumcontrolled
diet: the 250mg and 500mg tablets contain 48mg and 49mg of
or
similar
sodium,
preparations
equivalent to 2.4%
that
and
lower
2.5%
stool
of the recommended
pH: possible
maximum
reduction
daily
of
mesalazine intake for sodium. release Urine from may granules be discoloured due to red-brown decreased after pH contact caused with by
bacterial sodium hypochlorite metabolism bleach of lactulose. used in toilets. With Interactions: concomitant Specific treatment interaction with
azathioprine, studies have not 6-mercaptopurine been performed. or thioguanine With concomitant consider treatment a possible with
increase azathioprine, in their 6-mercaptopurine myelosuppressive or thioguanine, effects. There consider is weak a possible evidence increase that
mesalazine their myelosuppressive might decrease effects. the anticoagulant There is weak effect evidence of warfarin. that mesalazine Use in
pregnancy might decrease and the lactation: anticoagulant There are effect no of adequate warfarin. data. Salofalk Do granules not use
(additionally): lactulose, or similar preparations which lower stool pH:
during pregnancy unless the potential benefit outweighs the possible
possible reduction of mesalazine release from granules due to decreased pH
risks. caused Limited by bacterial experience metabolism in the of lactulose. lactation Use period. in pregnancy Use during and lactation: breastfeeding
do not use only Salofalk if the during potential pregnancy benefit unless outweighs the potential the possible benefit risks; outweighs if the
infant the possible develops risks. Limited diarrhoea, experience breast-feeding the lactation should period. be Salofalk discontinued. should
Undesirable only be used during effects: breast-feeding Headache, if dizziness, the potential peri- benefit and outweighs myocarditis, the
abdominal possible risks; pain, if the diarrhoea, breast-fed dyspepsia, infant develops flatulence, diarrhoea, nausea, breast-feeding vomiting,
aplastic should be discontinued. anaemia, agranulocytosis, Undesirable effects: pancytopenia, altered blood counts neutropenia, (aplastic
leukopenia,
anaemia, agranulocytosis,
thrombocytopenia,
pancytopenia,
peripheral
neutropenia,
neuropathy, allergic
leukopenia,
and
thrombocytopenia), hypersensitivity reactions such as allergic exanthema,
fibrotic
drug fever,
lung
lupus
reactions
erythematosus
(including
syndrome,
dyspnoea,
pancolitis,
cough,
headache,
bronchospasm,
dizziness,
alveolitis, peripheral neuropathy, pulmonary peri- eosinophilia, and myo-carditis, lung infiltration, allergic and pneumonitis), fibrotic lung
acute reactions pancreatitis, (including dyspnoea, impairment cough, of renal bronchospasm, function including alveolitis, pulmonary acute and
chronic eosinophilia, interstitial lung infiltration, nephritis pneumonitis), and renal insufficiency, abdominal nephrolithiasis,
pain, diarrhoea,
dyspepsia, flatulence, nausea, vomiting, acute pancreatitis, cholestatic
hepatitis, hepatitis, rash, pruritus, photosensitivity – especially with preexisting
skin conditions, alopecia, severe cutaneous adverse reactions
(SCARs) including drug reaction with eosinophilia and systemic symptoms
(DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis
(TEN), arthralgia, myalgia, impairment of renal function including acute and
chronic interstitial nephritis and renal insufficiency, nephrolithiasis, asthenia,
fatigue, oligospermia (reversible), changes in hepatic function parameters,
photosensitivity
changes in pancreatic
especially
enzymes,
with
eosinophil
pre-existing
count
skin
increased.
conditions,
Legal
alopecia,
category:
POM. Cost (UK - basic NHS price; Ireland - PtW): Salofalk 250mg tablets
Stevens-Johnson
(100s) £16.19; €13.48.
syndrome
Salofalk
(SJS),
500mg
toxic
tablets
epidermal
(100s) £32.38.
necrolysis
Salofalk
(TEN),
1g
myalgia, tablets (90s) arthralgia, £58.50. Salofalk hypersensitivity 500mg granules reactions (100 sachets) such £28.74; as allergic €27.93.
exanthema, Salofalk 1000mg drug granules fever, lupus (50 sachets) erythematosus £28.74; €32.87. syndrome, Salofalk pancolitis, 1500mg
changes granules in (60 hepatic sachets) function £48.85; parameters, €49.66. Salofalk hepatitis, 3g granules cholestatic (60 hepatitis sachets)
and £97.70; oligospermia €101.64. (reversible), Product licence asthenia, number: fatigue, Salofalk changes 250mg in pancreatic tablets:
enzymes, PL10341/0004; eosinophil PA573/4/3. count Salofalk increased. 500mg Legal tablets: category: PL08637/0019. POM. Salofalk Basic
cost: 1g tablets: Salofalk PL08637/0027. 500mg granules, Salofalk pack size 500mg 100 sachets granules: - £28.74; PL08637/0007; €30.39.
PA573/3/1. Salofalk 1000mg granules: PL08637/0008; PA573/3/2. Salofalk
Salofalk 1000mg granules, pack size 50 sachets – £28.74; 32.87€.
1500mg granules: PL08637/0016; PA573/3/7. Salofalk 3g granules:
Salofalk PL08637/0025; 1.5g Granules, PA573/3/6. pack Product size 60 licence sachets holder: - £48.85; Salofalk €50.02. 250mg Salofalk tablets
3g in Granules the UK: Dr pack Falk size Pharma 60 sachets UK Ltd, - Bourne £97.70; End €102.62 Business (UK- Park, NHS Cores price; End IE
- Road, PtW). Bourne Product End, SL8 licence 5AS. Salofalk number: 500mg Salofalk and 1g tablets 500mg and granules all granules: –
PL08637/0007; Dr Falk Pharma GmbH, PA573/3/1. Leinenweberstr.5, Salofalk 1000mg D-79108 granules Freiburg, – PL08637/0008;
Germany. Date
PA573/3/2. of preparation: Salofalk January 1.5g 2023 granules PL08637/0016; PA573/3/7. Salofalk
3g granules PL08637/0025; PA573/3/6.Product licence holder: Dr Falk
Pharma Further GmbH, information Leinenweberstr.5, is available on D-79108 request. Freiburg, Germany. Date of
preparation: January 2022.
Further Adverse information events should is available be reported. on request. In the UK: Reporting forms
and information can be found at https://yellowcard.mhra.gov.
Adverse uk/ In events Ireland: should Reporting be reported. forms Reporting and information forms and can information be found
can at be https://www.hpra.ie/homepage/about-us/report-an-issue/
found at https://yellowcard.mhra.gov.uk/ (UK residents) or in
Ireland human-adverse-reaction-form
at https://www.hpra.ie/homepage/about-us/report-anissue/human-adverse-reaction-form
reported to Dr Falk Pharma UK Ltd Adverse at PV@drfalkpharma.co.uk.
events should also be
Adverse events should also be
reported to Dr Falk Pharma UK Ltd at PV@drfalkpharma.co.uk
References:
References: 1. Salofalk Granules. Summary of Product Characteristics.
1. 2. Salofalk Aldulaimi Granules. D et al. Summary Poster DRF16/057 of Product presented Characteristics. at the
2. Aldulaimi BSG Annual D et Meeting, al. Poster June DRF16/057 2016, Liverpool presented UK. at the BSG Annual
3. Meeting, Keil R et June al. Scand 2016, J Liverpool Gastroenterol UK. 2018; 21: 1-7.
3. Keil R et al. Scand J Gastroenterol 2018; 21: 1-7.
UC: ulcerative colitis
UC: ulcerative colitis
Date of preparation: March 2023
Date
UI--2300070
of preparation: March 2022
UI--2200080
To find out more about Salofalk Granules
watch this 60s animation

FEATURE
FATIGUE IN PATIENTS WITH
INFLAMMATORY BOWEL DISEASE—
STRONGLY INFLUENCED BY DEPRESSION
AND NOT IDENTIFIABLE THROUGH
LABORATORY TESTING: A CROSS-
SECTIONAL SURVEY STUDY
Victoria Uhlir 1 , Andreas Stallmach 1 and Philip Christian Grunert 1 *
Uhlir et al. BMC Gastroenterology (2023) 23:288 https://doi.org/10.1186/s12876-023-02906-0
RESEARCH
Background
GASTROENTEROLOGY TODAY – AUTUMN 2023
Abstract
Background: Fatigue is a debilitating and highly relevant symptom in
patients with inflammatory bowel disease (IBD). However, awareness of
fatigue and treatment options remains limited. This study was aimed at
elucidating the influence of disease activity and common complications
(pain, anemia, depression, anxiety and quality of life) on fatigue in patients
with IBD to identify potential interventional targets for treating physicians.
Methods: A cross-sectional survey including five questionnaires (HADS,
Fatigue Assessment Scale, McGill Pain Questionnaire, IBDQ and general
well-being) was performed on patients with IBD (n = 250) at a university
IBD clinic. Additionally, demographic data, laboratory data, IBD history,
treatment and current disease activity (Harvey-Bradshaw Index, partial
Mayo Score, calprotectin and CRP) were recorded.
Results: A total of 189 patients were analyzed (59.8% with Crohn’s
disease (CD) and 40.2% with ulcerative colitis (UC)).
A total of 51.3% were fatigued, and 12.2% were extremely fatigued.
Multiple factors showed significant correlations in univariate analysis.
Multivariate analysis revealed that fatigue was correlated with
depression (CD, p = 0.002; UC, p = 0.02), diminished quality of life
(CD, p = 0.015), female sex (CD, p = 0.015) and younger age (UC,
p = 0.024), whereas the influence of anemia or disease activity was
non-significant.
Conclusions: Fatigue is burdensome and highly prevalent in
patients with active and inactive IBD. Considerations for fatigue
treatment, beyond targeting inflammation and anemia, should include
investigation of underlying subclinical depression.
Keywords: Fatigue, Crohn’s disease, Ulcerative colitis, Depression
Inflammatory bowel diseases (IBDs) are relapsing inflammatory bowel
conditions characterized by unclear etiology and an unpredictable
disease course. In addition to inflammatory activity, psychosocial
symptoms such as fatigue, persistent and extreme forms of mental
and/or physical exhaustion, tiredness or weakness occur [1]. In some
patients, the psychosocial symptoms of fatigue, is one of the most
frequent symptoms in IBD. As many as 80% of patients with active
disease and about 60% of patients in remission report this symptom
and find it even more debilitating than urgency, diarrhea, flatulence
and pain [3]. If left untreated, fatigue can increase over time [4]. Further
studies from the USA and France have reported similar high incidence
of fatigue (45–65%) in Crohn’s disease (CD) and ulcerative colitis
(UC) [5, 6], at rates comparable to those observed with other chronic
diseases such as cancer, multiple sclerosis or rheumatoid arthritis [7].
Although fatigue is highly relevant [3, 8], it is not well understood by
patients or practitioners [9], and it has received insufficient attention in
previous years. One reason for the low recognition of fatigue in clinical
consultations might be that fatigue assessment is challenging and
not clearly defined. Particularly in time-limited outpatient visits, the
psychosocial aspects of disease may be neglected, despite their high
importance in patients with IBD [10].
In previous studies, fatigue has been associated with depression [11–13],
pain [14], anxiety [15, 16], low quality of life [12, 17], psychological wellbeing
[4, 18], anemia [8, 19], and sex [20, 21]. The influence of disease
activity is controversial. Some studies have reported that disease activity
is a relevant factor [16, 22]. Physicians’ current management of fatigue
consists primarily of addressing inflammatory activity and nutritional
deficits. However, fatigue is highly prevalent even in quiescent disease
[2, 7, 23], at levels above those in healthy controls [2], and an increase in
*Correspondence:
Philip Christian Grunert philip.grunert@med.uni-jena.de
1
Department of Internal Medicine IV, Jena University Hospital, Universitätsklinikum Jena, Am Klinikum 1, 07747 Jena, Germany
12

FEATURE
fatigue over time is independent of disease pattern [4]. Thus, the causes
can be assumed to be multifactorial, and the dependence of fatigue on
potential influencing factors must be ruled out.
and ≥ 35 points indicating extreme fatigue. In a comparison of six
different fatigue questionnaires, the FAS has been found to be the
most promising measure of fatigue with good reliability and validity [26].
The aim of this study was to further elucidate the influence of disease
activity and common complications, such as pain, anemia, depression,
anxiety and decreased quality of life, on fatigue in patients with
IBD, to identify potential interventional targets for daily practice. In
a cross-sectional study, a sizeable IBD cohort was assessed with
the Fatigue Assessment Scale (FAS), IBD disease activity clinical
scores, paraclinical activity parameters and a large set of validated
questionnaires.
Patients and methods
Study population
This cross-sectional paper-based survey study was performed at the
Department of Internal Medicine, Jena University Hospital, a third-level
IBD clinic with approximately 2,100 patients with IBD. Patients were
recruited by the hospital staff during outpatient visits.
The inclusion criteria were 1) patients 18 years of age and older, 2)
diagnosis of Crohn`s disease (CD) or ulcerative colitis (UC) and 3)
German language proficiency.
Data collection
A total of 250 patients were asked to participate in the study between
June 27, 2018 and November 11, 2018. After providing written
consent, the patients completed five questionnaires evaluating
fatigue, depression and anxiety, pain, health related quality of life and
general well-being. Additionally, demographic information on sex, age,
occupation and current medications was recorded. Disease activity
was assessed by the treating physician. Laboratory values were
obtained from blood results measured no more than 4 weeks before or
after the appointment. Patients were included in the analysis when at
least 95% of questionnaire items were completed.
Measurements and instruments
Ascertainment of anxiety and depression
Anxiety and depression were assessed with the German version of
the Hospital Anxiety and Depression Scale, a 14-item self-reported
questionnaire with seven items each for the dimensions of depression
(HADS-D) and anxiety (HADS-A). Each item is rated 0–3 according to
severity, thus resulting in scores of 0–21 for each dimension [15]. A
score of 8–10 indicates suspicion, and a score > 10 points indicates
a disorder, of either anxiety or depression. This scale has been widely
used in patients with IBD [11, 13, 15, 16].
Ascertainment of quality of life
The Inflammatory Bowel Disease Questionnaire (IBDQ) is a disease
specific instrument used to assess the health-associated quality of life
(QoL) in patients with IBD. We used the German version, which has been
validated by Janke et al. It contains 32 items, each ranging from 1 (worst)
to 7 (best), and assesses the QoL in four dimensions (bowel, systemic,
emotional and social well-being) and provides a total score. Higher
scores indicate better QoL [31]. For our correlations, we used only the
total score.
Ascertainment of pain
The Short-Form McGill Pain Questionnaire is a well-established and
widely used measure to evaluate pain [32, 33]. It consists of three
parts. The first part assesses pain with adjectives, each graded
from 0 (none) to 3 (severe), thus illustrating the sensory (11 Items)
and affective (4 Items) component of pain (pain rating index). In
the second part, pain is quantified on a 0–100 Visual analogue Scale
(VAS). The present pain intensity is graded on a 5-point scale from
0 (no pain) to 5 (excruciating) in the third part. The scores for the
questionnaire can range from 0 to 45 on the pain rating index; from 0
to 10 cm on the VAS; and from 0 to 5 on present pain intensity.
Ascertainment of general well‐being
Patients were asked to rate their current general well-being on a Global
Assessment Scale ranging from 0 (very poor) to 100 (very good).
Clinical evaluation of disease activity
Disease activity in CD was assessed with the Harvey-Bradshaw Index
(HBI) [24]. Scores < 5 points indicated remission, 5–7 points indicated
mild disease, and higher scores indicated severe disease. UC disease
activity was graded with the partial Mayo Score (pMayo) [25]. Scores
< 2 points indicated remission, 2–4 points indicated mild disease, 5–6
points indicated moderate disease, and 7–9 points indicated severe
disease. Because the UC population was relatively small, we decided
to include patients with moderate to severe disease in one group, to
achieve better evaluation quality.
Ascertainment of fatigue
The FAS is a unidimensional ten item fatigue scale, which has
previously been used for the general public [26, 27] and for more than
26 other chronic diseases [27–30]. Each item is rated from 1 (never) to
5 (always), thus resulting in a total score ranging from 10 to 50 points,
with 10–21 points indicating no fatigue, 22–34 points indicating fatigue
Clinical laboratory values
To identify anemia, we evaluated hemoglobin (Hb), mean corpuscular
volume and mean corpuscular hemoglobin. Systemic inflammation was
assessed on the basis of the C-reactive protein (CRP), which we rated
as normal for all values under 7 mg/l. For IBD specific inflammation, we
used fecal calprotectin, a surrogate parameter for mucosal inflammation.
Values under 100 mg/kg stool were rated as normal/remission, whereas
values above 100 mg/kg indicated mucosal inflammation [34].
Data analysis
Descriptive analysis was performed with simple statistical standards,
such as percentages and mean values. Bar charts, histograms, and
box plots with percentages were used for presentation.
All metric scaled scores and age were tested with the determined
fatigue score with Pearson`s correlation coefficient and are presented
in scatter plots. Values above 0.5 indicated a strong effect.
GASTROENTEROLOGY TODAY – AUTUMN 2023
13

FEATURE
a N number of patients included for analysis
Table 1 Socio-demographic characteristics
CD N a UC N a Total N a
Socio-demographic characteristics
Total number of patients 113 (59.8%) 76 (40.2%) 189 189
Age 38 (18 -74) 47 (19–80) 40 (18–80) 189
Sex female/male 59/54 30/46 89/100 189
Employed 73 (67.6%) 108 45 (62.5%) 72 118 (65.6%) 180
Disease activity (HBI/partial Mayo) 104 71 175
Remission 59 (56.7%) 32 (45.1%) 91 (52.0%)
Mild disease 22 (21.2%) 23 (32.4%) 45 (25.7%)
Moderate to severe disease 23 (22.1%) 16 (22.5%) 39 (22.3%)
IBD Characteristics (Montreal) 112 76
Age at Diagnosis
A1 < 17 years 21 (18.8%)
A2 17–40 years 68 (60.7%)
A3 > 40 years 23 (20.5%)
Location (CD = L, UC = E)
L1 Terminal Ileum / E1 Proctitis 22 (19.6%) 2 (2.6%)
L2 Colon / E2 Left-sided 28 (25%) 41 (53.9%)
L3 Ileocolonic / E3 Pancolitis 47 (42%) 29 (38.2%)
Upper and lower GI-tract (+L4) / Ileal pouch 15 (13.4%) 4 (5.3%)
Behavior
B1 non-stricturing/non-penetrating 39 (34.8%)
B2 stricturing 30 (26.8%)
B3 penetrating 16 (14.3%)
B3p perianal disease 27 (24.1%)
Table 2 Results of psychometric tests and laboratory values
CD SD Min Max UC SD Min Max Total SD Min Max
GASTROENTEROLOGY TODAY – AUTUMN 2023
Psychosocial factors (N a )
FAS (189)
No fatigue 41 (36.3%) 28 (36.8%) 69 (36.5%)
Fatigue 60 (53.1%) 37 (48.7%) 97 (51.3%)
Extreme fatigue 12 (10.6%) 11 (14.5%) 23 (12.2%)
Mean value fatigue score 24.72 7.27 10 40 24.71 7.54 12 43 24.71 7.36 10 43
IBDQ10) 20 (17.9%) 18 (24.0%) 38 (20.3%)
HADS-D (depression) b (187) 5.04 4.1 0 17 5.41 3.78 0 16 5.19 3.96 0 17
Indicating depression (>10) 15 (13.5%) 7 (9.2%) 22 (11.8%)
McGill Pain Questionnaire (179)
Total pain none/ low – mild 35 (32.7%) 26 (36.1%) 61 (34.1%)
Total pain disstressing or worse 50 (46.7%) 32 (44.5%) 82 (45.8%)
Sensoric component of pain b (181) 5.59 5.4 0 21 4.75 5.78 0 25 5.25 5.56 0 25
Affective component of pain b (181) 2.63 3.08 0 12 2.12 2.56 0 11 2.43 2.89 0 12
Current pain on VAS b (182) 1.94 2.26 0 8.3 1.16 1.73 0 7.2 1.6 2.06 0 8.3
Laboratory values (N a )
Anaemia (169) 33 (33.0%) 28 (40.6%) 61 (36.1%)
CRP > 7 (163) 28 (28.9%) 16 (24.2%) 44 (27.0%)
Fecal calprotectin > 100 mg/kg (60) 18 (46.2%) 17 (81.0%) 35 (58.3%)
a N = number of patients included for analysis
b Mean value
14

FEATURE
Fig. 1 Mean fatigue scores (FAS), separated by IBD type. Data is grouped boxplots. N = 189
Table 3 Total fatigue score, tested against demographic factors/
laboratory values with Mann–Whitney U-test
p-value = p < 0.001
N a =
Employed b = employed, students and trainees
Unemployed c = unemployed and retired
Total fatigue score value
Factors N a median (IQR)
For mean value comparison, the variables to be tested were divided
into groups, which were tested against each other on the basis of the
achieved fatigue score. The groupings were as follows.
p-value
Anemia
No 108 24 (19–30.75) 0.538
Yes 61 24 (20–29.5)
CRP
Normal 119 24 (19–31) 0.109
Elevated 44 22.5 (18–28)
Fecal calprotectin
Normal 25 25 (20–30.5) 0.898
Elevated 35 24 (19–31)
Sex
Female 89 27 (23–31.5) < 0.001
Male 100 21 (18–28)
Diagnosis
CD 113 24 (19.5–30) 0.838
UC 76 24 (18–30.5)
Employment status
Employed B 134 24 (20–29) 0.357
Unemployed C 46 25.5 (18–33)
“elevated”; anemia: “yes” vs “no”; sex: “male” vs “female”; diagnosis:
“CD” vs “UC”; disease activity: “remission” vs “moderate to severe
disease”; anxiety and depression: “inconspicuous” vs “conspicuous,
severe to very severe symptoms”; and overall assessment of intensity
of pain: “non-low/mild” vs “distressing or worse.” Group analysis
was performed with the Mann–Whitney U-test. values < 0.05 were
considered significant. The Kruskal–Wallis test was used to assess
fatigue differences within the disease location, behaviour and age at
diagnosis groups.
For nominal (anemia, CRP elevation or fecal calprotectin elevation) or
ordinal (anxiety, depression, disease activity, quality of life or total pain)
variables, rank chi squared test (with trend test from three variables)
was performed, and cross tables were created. values < 0.05 were
considered significant.
To avoid a high number of missing cases in multiple linear regression
analysis, we conducted a univariate analysis for each variable to screen
for significant factors correlating with fatigue. For all metric scores
(HBI, pMayo, HADS-A/D, IBDQ, current pain, total pain and GAS) and
age, Pearson´s correlation coefficient was used. All nominal factors
(anemia, CRP elevation, fecal calprotectin elevation, sex and diagnosis,
surgery, medication, stoma) were tested by median comparison with
Mann– Whitney U-test. All variables showing a significant correlation (
< 0.05) in the univariate analysis, as well as sex and age, were included
in multiple linear regression analysis. Multiple regression analysis was
performed for CD and UC separately. All variables were tested for
collinearity. Analyses were performed in IBM SPSS Statistics version
25 (IBM Corp., Armonk, NY, USA).
Ethical considerations
GASTROENTEROLOGY TODAY – AUTUMN 2023
Laboratory values for CRP and fecal calprotectin: “normal” vs
Ethical approval was granted by the Ethics Committee of the Jena
15

FEATURE
Fig. 2 Mean fatigue scores (FAS), separated by IBD type and sex. Data is displayed as grouped boxplots. N = 189
GASTROENTEROLOGY TODAY – AUTUMN 2023
Table 4 Correlations among total scores of disease activity,
psychosocial factors and age, and the FAS score
p-value = p < 0.001
a
N =
University Hospital, Jena, Germany (5530– 05/18), and all patients provided
signed informed consent, according to the Declaration of Helsinki.
Results
A total of 250 patients were asked to participate in the study; 210
patients consented to participate, among whom a total of 189 patients
(76% response rate) completed at least 95% of the questionnaire
items and thus were included in the analysis. A total of 113 (59.8%)
patients had CD, and 76 (40.2%) patients had UC. Clinical and sociodemographic
characteristics are presented in Table 1. The results of
psychometric testing and laboratory values classified by type of IBD
are shown in Table 2.
Prevalence and severity of fatigue
Total fatigue score value
Total score value N a Pearson
correlation p-value R2 - value
HBI (for CD) 104 0.466 < 0.001 0.217
Partial Mayo Score (for UC) 71 0.183 0.183 0.026
HADS-A 187 0.616 < 0.001 0.379
HADS-D 187 0.679 < 0.001 0.46
IBDQ 186 -0.682 < 0.001 0.465
Current pain (McGill-Pain-Q.) 182 0.358 < 0.001 0.128
Total pain (McGill-Pain-Q.) 181 0.39 < 0.001 0.152
GAS 178 -0.562 < 0.001 0.316
Age 189 -0.012 0.869 1.449
The mean FAS fatigue scores were 24.72 (median: 24, IQR: 19,5–30)
and 24.71 (median 24, IQR: 18–30,5) for CD and UC, respectively (Fig.
1), and no statistical difference between diagnoses was observed ( =
0.838, Table 3). Two-thirds of patients were either fatigued (CD: 53.1%,
UC: 48.7%) or extremely fatigued (CD: 10.7%, UC: 14.5%). Fatigue
was significantly more frequent in women (80,9%) than in men (48,0%)
(median fatigue score 27 vs 21, < 0.001, Table 3, Fig. 2). Because we
did not find significant differences across IBD subtypes in univariate
analyses for all factors, we decided not to distinguish by diagnosis,
except for disease activity, for clarity of presentation in the tables.
Fatigue and disease characteristics
Fatigue was more often present in patients with moderate to severe
disease activity than in patients in remission (CD: 95.7% vs 46.6%,
UC: 75% vs 62.5%). This finding was significant in only CD ( < 0.001)
but not UC ( = 0.80). In CD, 82.1% of the patients without fatigue
were in remission, whereas 54.5% of those with extreme fatigue
had moderate to severe disease. This weak positive correlation was
statistically significant in univariate analysis ( < 0.001). Regarding
disease characteristics beyond disease activity, no correlations were
found between fatigue and age at diagnosis (H(2) = 0.183, = 0.913),
disease location (H(3) = 1.09, = 0.779), or disease behaviour (H(3) =
2.36, = 0.501) in patients with Crohn’s disease (CD) or disease location
(H(3) = 0.507, = 0.917) in patients with ulcerative colitis (UC). In the HBI
documented complications for CD (fistulas, erythema nodosum etc.)
did not correlate with higher levels of fatigue. 22 patients reported
having undergone bowel surgery. There was no significant influence
of surgery on fatigue ( = 0.864). 5 patients had a stoma which also
did not impact fatigue scores ( = 0.881). IBD specific medication did
not influence fatigue levels (any IBD medication n = 162, p = 0.108;
biologics n = 89, p = 0.351; mesalazine n = 64, p = 0.555; thiopurines
n = 28, p = 0.439; steroids n = 48, p = 0.724).
Psychosocial factors associated with fatigue
Univariate factor analysis with Pearson´s correlation coefficient showed
that anxiety, depression, health related quality of life, general well-being
and pain were associated with the presence of fatigue and total fatigue
score. The strongest correlations were found for quality of life and
depression (Table 4, Figs. 3 and 4).
Fatigue and anxiety
Patients without conspicuous anxiety symptoms had significantly lower
16

FEATURE
Fig. 3 Correlation of fatigue score (FAS) and depression score (HADS-D), separated by diagnosis.
Data is displayed as grouped scatter plot. N = 187
mean fatigue scores than patients with conspicuous anxiety symptoms
(median fatigue scores: 21 vs 32, p < 0.001). A total of 83.8% of
patients without fatigue showed unremarkable anxiety symptoms,
whereas 60.9% of patients with extreme fatigue were classified as
anxious with HADS-A (p < 0.001).
Fatigue and depression
Similar strong effects were found regarding depression. Whereas
patients without depression had median fatigue scores of 22 points,
the group classified as depressed according to HADS-D had a
median fatigue score of 33 points (p < 0.001). Whereas 95.6% of
the group without fatigue had no quantifiable depressive symptoms,
the depression was severe to very severe in 43.5% of the extremely
fatigued group.
Fig. 4 Correlation of fatigue score (FAS) and depression score (HADS-D), separated by diagnosis.
Data is displayed as grouped scatter plot. N = 187
Fatigue and HRQoL
Patients with fatigue or extreme fatigue significantly more often had
low scores for the magnitude of active disease (IBDQ < 171) (extreme
fatigue: 100%, fatigue: 71.9%, no fatigue: 25.4%, p < 0.001). A total of
64.9% of the patients with IBDQ scores > 171 (suggestive of remission)
had “no fatigue.” In contrast, 84.4% of the patients with low IBDQ
scores experienced either fatigue or extreme fatigue. The majority of
the 32 items and all of the 4 domains of the IBDQ showed a significant
correlation with fatigue, as determined by Pearson’s correlation
coefficient (Additional file 1). There were some exceptions, including
UC items 1 (stool frequency), 5 (loose stools), 7 (worried about
surgery), 17 (passing gas), 22 (rectal bleeding) as well as 26 (soiling),
and CD item 22 (rectal bleeding). The strongest correlations for fatigue
were observed for item 2 (tired / worn out) (UC: r(74) = -0.717, p = <
GASTROENTEROLOGY TODAY – AUTUMN 2023
17

FEATURE
Table 5 Multiple linear regression analysis of factors associated with total fatigue score
Crohn´s disease
Ulcerative colitis
Factors
(95%CI)
p-value*
p-value*
Female vs male 2.333 (0.466–4.199) 0.015 1.603 (-1.270–4.476) 0.268
Age 0.067 (0.002–0.136) 0.057 -0.109 (-0.202—0.015) 0.024
HBI/Partial Mayo Score -0.223 (-0.535–0.090) 0.160 -0.593 (-1.270–0.084) 0.085
HADS-D 0.613 (0.231–0.996) 0.002 0.756 (0.126–1.386) 0.020
HADS-A 0.177 (-0.187–0.541) 0.337 0.470 (-0.011–0.950) 0.055
IBDQ -0.113 (-0.186–-0.041) 0.003 -0.032 (-0.110–0.046) 0.415
GAS 0.010 (-0.063–0.082) 0.794 -0.019 (-0.105–0.067) 0.663
Total pain (McGill-Pain-Q.) 0.058 (-0.104–0.221) 0.477 -0.051 (-0.246–0.145) 0.606
Current pain (McGill-Pain-Q.) -0.168 (-0.949–0.613) 0.670 0.576 (-0.399–1.546) 0.239
* = p < 0.05
GASTROENTEROLOGY TODAY – AUTUMN 2023
0.001; CD: r(111) = -0.750, p = < 0.001), item 6 (energy) (UC: r(74) =
-0.655, p = < 0.001); CD: r(110) = -0.641, p = < 0.001) and item 15
(depressed / discouraged) (UC: r(74) = -0.686, p = < 0.001;CD: r(112) =
-0.653, p = < 0.001).
Fatigue and general well‐being
Although a wider variation was observed than that in other factors, a
strongly significant, anti-proportional correlation was found ( R2 = 0,316,
p < 0.001, Table 4) between the total fatigue score and the GAS score.
Fatigue and pain
Pearson’s correlation coefficient indicated linear correlations of current
pain intensity on the VAS ( R2 = 0.128, p < 0.001, Table 4) with the
total verbal pain score ( R2 = 0.152, p < 0.001, Table 4) and the total
fatigue score. The subjective overall assessment of the pain intensity
caused by the disease indicated that 52.3% of patients who did not
have fatigue classified their pain as low or mild. In contrast, 77.2% of
the patients with extreme fatigue reported that their pain intensity was
distressing or worse (p < 0.001).
Fatigue and laboratory values
Univariate factor analysis of the total fatigue score and laboratory
values is shown in Table 3. No statistical differences were found
regarding anemia, elevated CRP or elevated fecal calprotectin. A total
of 36.1% (61) of participants had anemia. Analysis according to fatigue
indicated no significant difference between groups: 62.3% of the
anemic patients and 63.9% of the non-anemic patients had fatigue (p =
0.437). In addition, the inflammatory values in the blood and stool were
not found to be predictive factors for fatigue (p = 0.057; p = 0.27).
Multivariate analysis
In the multivariate analysis, we stratified by IBD diagnosis and
included all factors that were significant in the univariate analysis as
well as sex and age (Table 5). After controlling for each of the other
variables, sex (p = 0.015), depression (p = 0.002) and quality of life (p
= 0.003) in CD, and age (p = 0.024) and depression (0.02) in UC were
significantly associated with fatigue. Trends were observed for age
(p = 0.057) in CD and for anxiety (p = 0.055) in UC. Unexpectedly, an
antiproportional trend was found for disease activity and fatigue in UC.
All other factors were found to be confounders. The results are shown
in Table 5. Although association with sex was highly significant over
both diagnoses in univariate analysis, no correlation was observed for
UC in regression analysis. In contrast, age was not significant in the
univariate analysis but was significant in regression analysis for CD.
Discussion
Fatigue in patients with IBD remains poorly understood. This crosssectional
study of 189 patients with IBD, aimed to investigate the
prevalence of fatigue, explore its associations with various factors, and
identify important implications for clinical practice. It indicated three
major findings. First, fatigue was highly prevalent: 63.5% of patients
with IBD experienced either fatigue or severe fatigue, regardless of
disease type and activity. Second, to address fatigue, physicians
should look beyond laboratory parameters, because anemia and
lab values which reflect disease activity do not reliably correlate with
fatigue. Third, the diagnostic workup of patients presenting with fatigue
should include screening for depression.
In this study, the observed prevalence of fatigue in patients with IBD
was 63.5% (51.3% with fatigue and 12.3% with severe fatigue)—a
percentage four times higher than that reported in the general
population [35]. The FAS results in patients with IBD are consistent with
those in previously published studies using other fatigue instruments
[5, 6, 19, 36]. In line with findings from previous studies, no differences
between the type of IBD and the occurrence or severity of fatigue were
found [15, 16, 19, 22]. The prevalence of fatigue in patients with IBD in
remission was approximately 50% in our study. Nearly all past studies
have reported that a large number of patients in remission still have
fatigue [4, 13, 15]. Therefore, the fatigue response may be independent
of the degree of intestinal inflammation and may be signaled through
other pathways [13].
Management of fatigue in patients with IBD is challenging. If following
guidelines, laboratory testing for, and supplementing with, vitamin B12,
folate and iron are recommended [37].
Anemia is one of the most frequent complications in patients with IBD
[38, 39]. However, in this study, no association was found between
the presence of anemia and fatigue, as 62.3% of the anemic patients
and 63.9% of the non-anemic patients experienced fatigue. Conflicting
results have been reported [2, 8, 9, 37, 40], but, the majority of
18

FEATURE
studies are in agreement with our findings [13, 15, 19, 22, 41–43].
Vitamin B12, folate and iron levels were not assessed in the current
study, thus, subclinical deficiencies may have an impact. Likewise, a
recent randomized controlled trial demonstrated the effectiveness of
high-dose oral thiamine for the treatment of fatigue in patients with
quiescent IBD [44].
The influence of disease activity on fatigue development has been
investigated in previous studies. Most studies that performed multivariate
regression analysis, to account for possible confounders, did not find an
association between fatigue and disease activity, in accordance with our
data [2, 13, 15, 19, 45, 46]. Among the studies that found associations
for IBD [4, 17, 42, 47] or specific subtypes of IBD [16, 48], two studies
did not correct for psychosomatic dimensions (e.g., pain, anxiety and
depression) [17, 42], and those that did correct have found conflicting
results [4] or no correlation with disease activity after multivariate analysis
[47, 48]. Studies that have used the same activity scores (HBI and partial
Mayo) have come to the same conclusion that disease activity alone is
not the main driver of fatigue [13, 15].
In agreement with the observations of clinical scores, fecal
calprotectin, which correlates well with disease activity [34], and CRP
elevation did not show a correlation with fatigue in both CD or UC in
this study. This finding is consistent with previous studies [16, 22, 42,
47]. Huppertz-Hauss et al. and Bager et al. have described that the
perceived disease’s symptom burden, rather than its biochemical
markers, correlates with fatigue [16, 42]. Further analysis of the IBDQ
results in this study revealed that patient-reported items indicating
active disease, such as rectal bleeding (UC/CD), loose stools (UC), and
increased stool frequency (UC) did not show a significant correlation
with the level of fatigue. However, items related to disease burden,
such as disrupted / restricted participation in activities, embarrassment
and emotional aspects did correlate significantly. The findings of
Jelsness-Jorgensen et al. indicating that patients with inactive IBD
and additional irritable bowel syndrome have higher fatigue levels than
those without, underlines the influence of perceived burden rather than
actual inflammatory activity [49].
In our study, depression, measured by the HADS-D, showed
the strongest associations with fatigue in both CD and UC in the
multivariate analysis. Similar results have been reported by previous
studies [7, 13, 15, 46, 50, 51]. Depression and fatigue have common
behavioral, affective and cognitive characteristics; furthermore, they
may even share similar causal pathways [7, 46, 51]. Truyens et al.
[52] suspected fatigue to be a symptom of underlying undetected
depression. This hypothesis was supported by our study, in which
100% of patients with conspicuous values on the HADS-D scale
had fatigue. The connection between depression and IBD through
the gut-brain-axis has been shown to be bidirectional. Severe IBD
has been shown to impact psychology and is associated with newonset
depression [53]. Conversely, depression can negatively affect
the course of IBD [52, 54–56]. Hence identifying and appropriately
addressing depression in patients with IBD are crucial. Patients
reporting symptoms of fatigue should be screened for concomitant
depression, particularly when the common fatigue work-up is
unremarkable.
Despite strong correlations in the univariate analysis, the variables
anxiety, current well-being and pain did not remain significant in the
multivariate analysis and were found to be confounders. Nevertheless,
they should not be completely disregarded in the assessment of
fatigue, regarding anxiety there was a tendency for correlation in the
multivariate analysis in UC. Agerelated effects on fatigue exhibited a
weak and inconsistent correlation, possibly stemming from variations in
age and gender distribution between the two disease types [42].
As in any scientific investigation, this study has several limitations. The
participants in this study were patients from the outpatient department
of a tertiary referral center. This may limit the generalizability of the
findings to the entire IBD population, e.g., the level of fatigue among
outpatients in an oncological study was observed to be higher
compared to that of inpatients [57]. Laboratory values were recorded
not numerically but only nominally (increased or not increased). In
addition, the data were laboratory values from a maximum of 4 weeks
before or after completion of the questionnaires, thus potentially
leading to inaccuracy, given that therapeutic interventions or flares
might have occurred during the period between sample collection
and assessment of fatigue. Moreover, most surveyed patients were in
remission (52%) or had only mild symptoms (25.7% mild disease).
The FAS, which has been shown to be a reliable instrument to assess
fatigue [26, 27], is unidimensional, thereby hindering direct comparison
with previous IBD studies that have used other (multidimensional)
fatigue scores. The strengths of the study include the broad
assessment of possible factors influencing fatigue through a broad set
of validated questionnaires as well as clinical and paraclinical data in
almost 200 patients with IBD.
Conclusions
In conclusion, we demonstrated that fatigue is burdensome and highly
prevalent in patients with IBD. Fatigue should receive attention in
patients with active disease as well as disease in remission, because it
did not significantly correlate with anemia or disease activity. Thus, we
recommend implementing an easy to fill-out fatigue survey, such as the
FAS which takes about 2 min to complete, in daily practice. The strong
associations with depression highlight the importance of investigating
and addressing possible underlying sub-clinical depression in patients
reporting fatigue symptoms.
Abbreviations
CD Crohn’s disease
CRP C-reactive protein
FAS Fatigue Assessment Scale
GAS Global Assessment Scale
HADS Hospital Anxiety and Depression Scale
Hb Hemoglobin
HBI Harvey-Bradshaw Index
HRQoL Health related quality of life IBD Inflammatory bowel disease
IBDQ Inflammatory Bowel Disease Questionnaire p
Mayo Partial Mayo Score
UC Ulcerative colitis
VAS Visual analogue scale
Supplementary Information
The online version contains supplementary material available at
https://doi.org/10.1186/s12876-023-02906-0.
Additional file 1. Correlation between IBDQ items / domains and the
total fatigue score by PearsonÅLs correlation coefficient.
GASTROENTEROLOGY TODAY – AUTUMN 2023
19

FEATURE
GASTROENTEROLOGY TODAY – AUTUMN 2023
Acknowledgements
We wish to thank all the IBD patients for completing the questionnaires.
We thank Dr.-Ing., M.Sc. Heike Hoyer and Jana Ziegler (both: Institute of
Medical Statistics, Computer and Data Sciences, University Clinic Jena,
Germany) for support with data analysis.
Authors’ contributions
VU and PCG have made substantial contributions to the conception or
design of the work, the acquisition, analysis and interpretation of data for
the work. They drafted the work. AS has made substantial contributions
to the conception or design of the work. He revised the work critically
for important intellectual content. All authors gave final approval of the
version to be published and agreed to be accountable for all aspects of
the work in ensuring that questions related to the accuracy or integrity of
any part of the work are appropriately investigated and resolved.
Funding
Open Access funding enabled and organized by Projekt DEAL. No
funding was sourced for this project.
Availability of data and materials
The datasets used and analysed during the current study are available
from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
Ethical approval was granted by the Ethics Committee of the Jena
University Hospital, Jena, Germany (5530–05/18), and all patients
provided signed informed consent for participation in the study,
according to the Declaration of Helsinki.
Consent for publication
Not applicable.
Competing interests
VU reports no competing interests. AS reports research funding from
AbbVie and Celltrion and has received lecture fees from AbbVie, Amgen,
Astellas, Biogen, Celltrion, Institut Allergosan, Janssen, Falk Foundation,
Ferring, MSD, Recordati Pharma, Streamed-Up, and Takeda, and
consulting fees from AbbVie, Astellas, Amgen, Biogen, CLS Behring,
Consal, Galapagos, Hexal, Janssen, MSD, Norgine, Pfizer Pharma,
Takeda, Pharmacosmos, and Tillots Pharma. PCG obtained consulting
fees from Janssen and Takeda and lecture fees and from AbbVie,
Janssen, Pfizer, Falk, and Takeda.
Received: 12 March 2023 Accepted: 25 July 2023
Published online: 22 August 2023
References
1. Dittner AJ, Wessely SC, Brown RG. The assessment of fatigue: a
practical guide for clinicians and researchers. J Psychosom Res.
2004;56(2):157–70.
2. Yoo S, Jung YS, Park JH, Kim HJ, Cho YK, Sohn CI, Jeon WK,
Kim BI, Park DI. Fatigue severity and factors associated with high
fatigue levels in Korean patients with inflammatory bowel disease.
Gut and liver. 2014;8(2):148–53.
3. Farrell D, McCarthy G, Savage E. Self-reported symptom burden
in individuals with inflammatory bowel disease. J Crohns Colitis.
2016;10(3):315–22.
4. Graff LA, Clara I, Walker JR, Lix L, Carr R, Miller N, Rogala L,
Bernstein CN. Changes in fatigue over 2 years are associated with
activity of inflammatory bowel disease and psychological factors.
Clin Gastroenterol Hepatol. 2013;11(9):1140–6.
5. Williet N, Sarter H, Gower-Rousseau C, Adrianjafy C, Olympie
A, Buisson A, Beaugerie L, Peyrin-Biroulet L. Patient-reported
outcomes in a french nationwide survey of inflammatory bowel
disease patients. J Crohns Colitis. 2017;11(2):165–74.
6. Hashash JG, Ramos-Rivers C, Youk A, Chiu WK, Duff K, Regueiro
M, Binion DG, Koutroubakis I, Vachon A, Benhayon D, et al.
Quality of sleep and coexistent psychopathology have significant
impact on fatigue burden in patients with inflammatory bowel
disease. J Clin Gastroenterol. 2018;52(5):423–30.
7. Czuber-Dochan W, Ream E, Norton C. Review article: description
and management of fatigue in inflammatory bowel disease.
Aliment Pharmacol Ther. 2013;37(5):505–16.
8. Gasche C, Lomer MC, Cavill I, Weiss G. Iron, anaemia, and
inflammatory bowel diseases. Gut. 2004;53(8):1190–7.
9. Czuber-Dochan W, Norton C, Bredin F, Darvell M, Nathan I, Terry
H. Healthcare professionals’ perceptions of fatigue experienced by
people with IBD. J Crohns Colitis. 2014;8(8):835–44.
10. Christensen KR, Ainsworth MA, Skougaard M, Steenholdt C,
Buhl S, Brynskov J, Kristensen LE, Jorgensen TS. Identifying and
understanding disease burden in patients with inflammatory bowel
disease. BMJ Open Gastroenterol. 2022;9(1):e000994.
11. Banovic I, Gilibert D, Jebrane A, Cosnes J. Diagnostic profiles
determined by the C.A.R.T procedure: IBD patients and fatigue.
J Health Psychol. 2012;17(4):500–8.
12. Piche T, Ducrotté P, Sabate JM, Coffin B, Zerbib F, Dapoigny
M, Hua M, Marine-Barjoan E, Dainese R, Hébuterne X. Impact
of functional bowel symptoms on quality of life and fatigue
in quiescent Crohn disease and irritable bowel syndrome.
Neurogastroenterol Motil. 2010;22(6):626-e174.
13. Grimstad T, Norheim KB, Isaksen K, Leitao K, Hetta AK, Carlsen
A, Karlsen LN, Skoie IM, Goransson L, Harboe E, et al. Fatigue in
newly diagnosed inflammatory bowel disease. J Crohns Colitis.
2015;9(9):725–30.
14. Jelsness-Jorgensen LP, Frigstad SO, Moum B, Grimstad T,
Opheim R, Jahnsen J, Bernklev T. Pain may be an important factor
to consider in inflammatory bowel disease patients troubled by
fatigue. United European Gastroenterol J. 2017;5(5):687–93.
15. Chavarria C, Casanova MJ, Chaparro M, Barreiro-de Acosta
M, Ezquiaga E, Bujanda L, Rivero M, Arguelles-Arias F, Martin-
Arranz MD, Martinez-Montiel MP et al: Prevalence and Factors
Associated with Fatigue in Patients with Inflammatory Bowel
Disease: A Multicenter Study. Journal of Crohn’s & colitis 2019.
16. Huppertz-Hauss G, Hoivik ML, Jelsness-Jorgensen LP, Opheim R,
Henriksen M, Hoie O, Hovde O, Kempski-Monstad I, Solberg IC,
Jahnsen J, et al. Fatigue in a population-based cohort of patients
with inflammatory bowel disease 20 years after diagnosis: the
IBSEN study. Scand J Gastroenterol. 2017;52(3):351–8.
17. Romberg-Camps MJ, Bol Y, Dagnelie PC, Hesselink-van de Kruijs
MA, Kester AD, Engels LG, van Deursen C, Hameeteman WH,
Pierik M, Wolters F, et al. Fatigue and health-related quality of life
in inflammatory bowel disease: results from a population-based
study in the Netherlands: the IBD-South Limburg cohort. Inflamm
Bowel Dis. 2010;16(12):2137–47.
18. Hindryckx P, Laukens D, D’Amico F, Danese S. Unmet
needs in IBD: the case of fatigue. Clin Rev Allergy Immunol.
2018;55(3):368–78.
19. Jelsness-Jorgensen LP, Bernklev T, Henriksen M, Torp R, Moum
BA. Chronic fatigue is more prevalent in patients with inflammatory
bowel disease than in healthy controls. Inflamm Bowel Dis.
2011;17(7):1564–72.
20. Bager P, Vestergaard C, Juul T, Dahlerup JF. Population-based
normative data for the inflammatory bowel disease fatigue scale -
IBD-F. Scand J Gastroenterol. 2018;53(10–11):1274–9.
21. Villoria A, Garcia V, Dosal A, Moreno L, Montserrat A, Figuerola A,
Horta D, Calvet X, Ramirez-Lazaro MJ. Fatigue in out-patients with
inflammatory bowel disease: prevalence and predictive factors.
PLoS ONE. 2017;12(7):e0181435.
22. Graff LA, Vincent N, Walker JR, Clara I, Carr R, Ediger J, Miller N,
Rogala L, Rawsthorne P, Lix L, et al. A population-based study
of fatigue and sleep difficulties in inflammatory bowel disease.
Inflamm Bowel Dis. 2011;17(9):1882–9.
23. Minderhoud IM, Oldenburg B, van Dam PS, van Berge
Henegouwen GP. High prevalence of fatigue in quiescent
inflammatory bowel disease is not related to adrenocortical
insufficiency. Am J Gastroenterol. 2003;98(5):1088–93.
24. Harvey RF, Bradshaw JM. A simple index of Crohn’s-disease
activity. Lancet (London, England). 1980;1(8167):514.
25. Lewis JD, Chuai S, Nessel L, Lichtenstein GR, Aberra FN,
Ellenberg JH. Use of the noninvasive components of the Mayo
score to assess clinical response in ulcerative colitis. Inflamm
Bowel Dis. 2008;14(12):1660–6.
20

FEATURE
26. De Vries J, Michielsen HJ, Van Heck GL. Assessment of fatigue
among working people: a comparison of six questionnaires.
Occup Environ Med. 2003;60(Suppl 1):i10-15.
27. Michielsen HJ, De Vries J, Van Heck GL. Psychometric qualities of
a brief self-rated fatigue measure: the fatigue assessment scale.
J Psychosom Res. 2003;54(4):345–52.
28. Drent M, Lower EE, De Vries J. Sarcoidosis-associated fatigue.
Eur Respir J. 2012;40(1):255–63.
29. Cumming TB, Mead G. Classifying post-stroke fatigue: optimal
cut-off on the fatigue assessment scale. J Psychosom Res.
2017;103:147–9.
30. Hendriks C, Drent M, Elfferich M, De Vries J. The fatigue
assessment scale: quality and availability in sarcoidosis and other
diseases. Curr Opin Pulm Med. 2018;24(5):495–503.
31. Janke KH, Klump B, Steder-Neukamm U, Hoffmann J, Hauser
W. Validation of the German version of the Inflammatory bowel
disease questionnaire (Competence Network IBD, IBDQ-D).
Psychother Psychosom Med Psychol. 2006;56(7):291–8.
32. Melzack R. The short-form McGill pain questionnaire. Pain.
1987;30:191–7.
33. Stein CM, Mendl G. The German counterpart to McGill pain
questionnaire. Pain. 1988;32:251–5.
34. Zittan E, Kelly OB, Gralnek IM, Silverberg MS, Hillary Steinhart
A. Fecal calprotectin correlates with active colonic inflammatory
bowel disease but not with small intestinal Crohn’s disease activity.
JGH Open. 2018;2(5):201–6.
35. Martin A, Staufenbiel T, Gaab J, Rief W, Brahler E: The assessment
of chronic fatigue: psychometric properties of the Fatigue Scale
(FS). Z Kl Psych Psychoth 2010, 39(1)(1):33–44.
36. Römkens TE, van Vugt-van Pinxteren MW, Nagengast FM,
van Oijen MG, de Jong DJ. High prevalence of fatigue in
inflammatory bowel disease: a case control study. J Crohns Colitis.
2011;5(4):332–7.
37. Kreijne JE, Lie MR, Vogelaar L, van der Woude CJ. Practical
guideline for fatigue management in inflammatory bowel disease.
J Crohns Colitis. 2016;10(1):105–11.
38. Rogler G, Vavricka S. Anemia in inflammatory bowel disease: an
underestimated problem? Front Med (Lausanne). 2014;1:58.
39. Goodhand JR, Kamperidis N, Rao A, Laskaratos F, McDermott
A, Wahed M, Naik S, Croft NM, Lindsay JO, Sanderson IR, et al.
Prevalence and management of anemia in children, adolescents,
and adults with inflammatory bowel disease. Inflamm Bowel Dis.
2012;18(3):513–9.
40. Niepel D, Klag T, Malek NP, Wehkamp J. Practical guidance for the
management of iron deficiency in patients with inflammatory bowel
disease. Ther Adv Gastroenterol. 2018;11:1756284818769074.
41. Bager P. Fatigue and acute/chronic anaemia. Dan Med J.
2014;61(4):B4824.
42. Bager P, Befrits R, Wikman O, Lindgren S, Moum B, Hjortswang
H, Hjollund NH, Dahlerup JF. Fatigue in out-patients with
inflammatory bowel disease is common and multifactorial. Aliment
Pharmacol Ther. 2012;35(1):133–41.
43. Gracie DJ, Williams CJ, Sood R, Mumtaz S, Bholah MH,
Hamlin PJ, Ford AC. Poor correlation between clinical disease
activity and mucosal inflammation, and the role of psychological
comorbidity, in inflammatory bowel disease. Am J Gastroenterol.
2016;111(4):541–51.
44. Bager P, Hvas CL, Rud CL, Dahlerup JF. Randomised clinical
trial: high-dose oral thiamine versus placebo for chronic fatigue
in patients with quiescent inflammatory bowel disease. Aliment
Pharmacol Ther. 2021;53(1):79–86.
45. van Hoogmoed D, Fransen J, Bleijenberg G, van Riel P. Physical
and psychosocial correlates of severe fatigue in rheumatoid
arthritis. Rheumatology (Oxford). 2010;49(7):1294–302.
46. Cohen BL, Zoëga H, Shah SA, Leleiko N, Lidofsky S, Bright R,
Flowers N, Law M, Moniz H, Merrick M, et al. Fatigue is highly
associated with poor health-related quality of life, disability and
depression in newly-diagnosed patients with inflammatory bowel
disease, independent of disease activity. Aliment Pharmacol Ther.
2014;39(8):811–22.
47. Artom M, Czuber-Dochan W, Sturt J, Murrells T, Norton C. The
contribution of clinical and psychosocial factors to fatigue in 182
patients with inflammatory bowel disease: a cross-sectional study.
Aliment Pharmacol Ther. 2017;45(3):403–16.
48. Jelsness-Jørgensen LP, Bernklev T, Henriksen M, Torp R, Moum
BA. Chronic fatigue is associated with impaired health-related
quality of life in inflammatory bowel disease. Aliment Pharmacol
Ther. 2011;33(1):106–14.
49. Jelsness-Jørgensen LP, Bernklev T, Moum B. Fatigue and diseaserelated
worries among inflammatory bowel disease patients in
remission; is it a reflection of coexisting IBS-like symptoms? A
short report. J Psychosom Res. 2012;73(6):469–72.
50. van Langenberg DR, Gibson PR. Factors associated with
physical and cognitive fatigue in patients with Crohn’s disease:
a cross-sectional and longitudinal study. Inflamm Bowel Dis.
2014;20(1):115–25.
51. Keightley P, Reay RE, Pavli P, Looi JC. Inflammatory bowel
disease-related fatigue is correlated with depression and gender.
Australas Psychiatry. 2018;26(5):508–13.
52. Truyens M, De Ruyck E, Gonzales GB, Bos S, Laukens D,
De Vos M. Prevalence of fatigue and unrecognized depression
in patients with inflammatory bowel disease in remission
under immunosuppressants and biologicals. J Clin Med.
2021;10(18):4107.
53. Guo L, Rohde J, Farraye FA. Stigma and disclosure in
patients with inflammatory bowel disease. Inflamm Bowel Dis.
2020;26(7):1010–6.
54. Mittermaier C, Dejaco C, Waldhoer T, Oefferlbauer-Ernst A,
Miehsler W, Beier M, Tillinger W, Gangl A, Moser G. Impact of
depressive mood on relapse in patients with inflammatory bowel
disease: a prospective 18-month follow-up study. Psychosom
Med. 2004;66(1):79–84.
55. Kuznicki P, Kempinski R, Neubauer K. The emerging role of mood
disorders in inflammatory bowel diseases. Adv Clin Exper Med.
2020;29(12):1505–10.
56. Moulton CD, Pavlidis P, Norton C, Norton S, Pariante C, Hayee B,
Powell N: Depressive symptoms in inflammatory bowel disease:
an extraintestinal manifestation of inflammation? Clinical and
experimental immunology 2019.
57. Hochman MJ, Wolf S, Zafar SY, Portman D, Bull J, Kamal AH.
Comparing unmet needs to optimize quality: characterizing
inpatient and outpatient palliative care populations. J Pain
Symptom Manage. 2016;51(6):1033–9.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
GASTROENTEROLOGY TODAY – AUTUMN 2023
21

NEWS
“We know that this can also have a
detrimental effect on their mental wellbeing.
“The rates of microscopic colitis are
increasing and are likely to grow further as
the population ages, so it’s crucial that we
identify risk factors, provide specific training
for healthcare providers, continue to raise
awareness and invest in research to improve
diagnosis and treatments.”
Chris Probert, professor of gastroenterology
at the University of Liverpool, added:
“Undiagnosed microscopic colitis can cause
years of unnecessary suffering.
“The diarrhoea symptoms tend to be
very severe and house-limiting, leading to
considerable distress for patients.
Concern over undiagnosed
cases of severe bowel
condition
Ella Pickover, PA Health Correspondent
Microscopic colitis is a debilitating condition
which leads to inflammation of the large
bowel, it can cause symptoms including
persistent watery diarrhoea, stomach pain,
fatigue, urgency to go to the toilet and waking
in the night to empty the bowel.
“It’s not clear why cases of the condition are
on the increase but it is likely to be due to a
mixture of increased awareness of symptoms
leading to more diagnoses and environmental
factors such as a potential side effect of
common prescription drugs such as some
antidepressants.
More must be done to stop people suffering
unnecessarily due to a lack of awareness
about a severe bowel condition, a charity
has warned.
Some 17,000 people are diagnosed with
microscopic colitis each year in the UK but
Guts UK believes the real figure could be a lot
higher due to high rates of misdiagnosis and
the complex way the condition is detected.
Unlike other inflammatory bowel diseases,
microscopic colitis cannot be seen on a
camera and requires a tissue sample to be
taken from the bowel and examined under
a microscope.
Because this step is not always completed,
many are left undiagnosed, Guts UK said.
Experts have also suggested that people
aren’t seeking help for symptoms because
they are embarrassed or, if they do, they’re
often misdiagnosed with irritable bowel
syndrome (IBS).
The charity said that once diagnosed, there
is an effective treatment for most people
as it called for more to be done to improve
diagnosis rates.
A previous study has shown that one-inthree
patients with the condition were initially
diagnosed with irritable bowel syndrome.
The charity said that previous estimates have
suggested that some 67,000 people could be
living with the condition in the UK, with more
women thought be affected.
It said that, despite misdiagnoses, cases
are on the rise – in the UK incidence rate of
microscopic colitis in 2016 was twice that
observed in 2009.
“It’s terribly sad that thousands of people
are suffering with the debilitating symptoms
of microscopic colitis,” said Julie Harrington,
chief executive of Guts UK.
“Most people with the condition can be easily
treated with a course of gut-specific steroids
or with symptom-relieving medicines but
getting a diagnosis is the first, essential step.
“People living with the condition but without
the benefit of a correct diagnosis and effective
treatments often can often feel very isolated
due to the urgent nature of their symptoms
and their need to be near to toilet facilities at
all times.
“The good news is that effective treatments
are available so people experiencing
symptoms could benefit enormously by
talking with their GP.”
One women, known only as Victoria, age
33 from London, was diagnosed with
microscopic colitis last year.
“I spent 12 years living with undiagnosed
microscopic colitis,” she said.
“On my worst days, I was going to the toilet
30 to 40 times per day and suffered from
awful stomach cramps.
“I ended up becoming agoraphobic because I
was so distressed. I went to the doctor again
and again but it took me all these years to get
a correct diagnosis. I even went to A&E but
was told it was ‘just IBS’ and I was sent home
with no treatment plan.
“The treatment I have received after getting
my diagnosis has changed my life. I feel like
I’ve regained some semblance of normal.”
Guts UK has created a new resource for
patients to find out more about the condition.
GASTROENTEROLOGY TODAY – AUTUMN 2023
23

NEWS
Severe bowel condition on
the rise in the UK
Many people suffer with the condition for years
but the correct diagnosis and treatment can
make a huge difference. [8]
continue to raise awareness and invest in
research to improve diagnosis and treatments.”
Professor Chris Probert, Professor of
• Resource for patients published by the national
charity Guts UK highlights the growing number
of microscopic colitis cases in the UK.
Victoria, age 33 from London, was diagnosed
with microscopic colitis last year. She said:
Gastroenterology at the University of
Liverpool said:
• The charity has raised concerns about the
number of people suffering with a misdiagnosis
or living with undiagnosed and debilitating
symptoms.
• 17,000 new cases are being diagnosed each
year, but the real number could be a lot higher.
Experts have raised concerns about the
number of people suffering with undiagnosed
microscopic colitis, a debilitating bowel condition
thought to affect thousands of adults in the UK.
The national charity Guts UK has published a
resource for patients during Microscopic Colitis
Awareness Week to raise awareness of the
disease and is calling for more research into
prevention, faster diagnoses and developments
in treatments.
“I spent 12 years living with undiagnosed
microscopic colitis. On my worst days, I was going
to the toilet 30 to 40 times per day and suffered
from awful stomach cramps. I ended up becoming
agoraphobic because I was so distressed. I went
to the doctor again and again but it took me all
these years to get a correct diagnosis. I even went
to A&E but was told it was ‘just IBS’ and I was sent
home with no treatment plan.
“By 2022 I became scared of eating in case
it triggered symptoms and my flare ups were
becoming more frequent. I felt more tired than I’d
ever felt in my life and completely hopeless. I was
also trying to parent my baby son while living with
the condition.
“The treatment I have received after getting my
diagnosis has changed my life. I feel like I’ve
regained some semblance of normal.”
“Undiagnosed microscopic colitis can cause years
of unnecessary suffering. The diarrhoea symptoms
tend to be very severe and houselimiting leading to
considerable distress for patients.
“It’s not clear why cases of the condition are on
the increase but it is likely to be due to a mixture
of increased awareness of symptoms leading to
more diagnoses and environmental factors such
as a potential side effect of common prescription
drugs such as some antidepressants.
“The good news is that effective treatments are
available so people experiencing symptoms could
benefit enormously by talking with their GP.”
Resources published in March 2022 by Guts UK
to raise awareness of microscopic colitis showed
that women are 700% more likely than men to
suffer with the condition.
Microscopic colitis is an inflammation of the large
intestine (bowel) that causes persistent, frequent
and watery diarrhoea (throughout the day and
night), stomach pain, fatigue, faecal incontinence
and weight loss. It is frequently misdiagnosed
and the prevalence of the condition is higher than
previously thought. [1]
Microscopic colitis is named because, unlike
other inflammatory bowel diseases, like Crohn’s
disease or ulcerative colitis, it can’t be diagnosed
with a colonoscopy alone and a sample of tissue
taken from the bowel must be examined under a
microscope to identify the condition. Because of
this, the disease is often misdiagnosed.
The causes of microscopic colitis are still unclear.
As it is a relatively new disease (first described
in 1976) it has led to a presumption that it is
environmental as opposed to genetic factors that
are responsible for its occurrence.
For more information visit gutscharity.org.uk
GASTROENTEROLOGY TODAY – AUTUMN 2023
Scientists estimate that around 67,000 people
are living with microscopic colitis in the UK or at
least 1 in 1,000 adults.[2][3] 17,000 new cases
are being diagnosed each year, but the real
number could be a lot higher because it’s often
underreported and misdiagnosed.[4]
A 2012 study showed that one in three patients
with microscopic colitis were initially incorrectly
diagnosed with Irritable Bowel Syndrome (IBS)
and “a large, hidden burden of undiagnosed and
untreated microscopic colitis likely exists in the
UK population owing to systematic misdiagnosis
of microscopic colitis as IBS.”[5][6]
Despite the missed diagnoses, cases of
microscopic colitis are on the rise globally. The
UK incidence rate of microscopic colitis in 2016
was twice that observed in 2009.[7]
Microscopic colitis is a leading cause of
diarrhoea in older adults and it can have a
devastating impact on a person’s quality of life.
Julie Harrington, CEO of Guts UK, said:
“It’s terribly sad that thousands of people
are suffering with the debilitating symptoms
of microscopic colitis. Most people with the
condition can be easily treated with a course of
gut-specific steroids or with symptom-relieving
medicines but getting a diagnosis is the first,
essential step.
“People living with the condition but without
the benefit of a correct diagnosis and effective
treatments often can often feel very isolated due
to the urgent nature of their symptoms and their
need to be near to toilet facilities at all times. We
know that this can also have a detrimental effect
on their mental wellbeing.
“The rates of microscopic colitis are increasing
and are likely to grow further as the population
ages, so it’s crucial that we identify risk factors,
provide specific training for healthcare providers,
#MicroscopicColitisAwareness
[1] Undiagnosed microscopic colitis: a hidden cause
of chronic diarrhoea and a frequently missed
treatment opportunity: https://fg.bmj.com/
content/11/3/228
[2] Aprox. 67,000 people are living with Microscopic
Colitis in the UK - around 58,600 women and
8,400 men.
[3] Microscopic colitis includes two related
inflammatory bowel disorders, lymphocytic
colitis and collagenous colitis that have a
combined prevalence of 103 cases per 100 000
population: May 2019.
[4] https://www.crohnsandcolitis.org.uk/aboutcrohns-and-colitis/publications/microscopiccolitis
[5] https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC3484793/
[6] https://drive.google.com/file/d/1XF-
FoJM3wGeoO1krPzh-aQiACXSYwPSf/
view?usp=sharing
[7] https://gut.bmj.com/content/66/Suppl_2/A156.1
[8] https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC8776530/
[9] 87.5% of people suffering with the condition are
female - most of whom are diagnosed between
the ages of 50 and 70.
24

Revolutionise Your Your IBD Revolutionise Management:
IBD Your IBD Revo M
BDoc IBDoc ® Calprotectin ® Calprotectin Home IBDoc Home Test ® Calprotectin with
Test with Hom IB
Swift, Swift, Direct Direct to Patient to Patient Swift, Delivery Direct Delivery to Patien
Discover the Discover future of
the future of
healthcare at healthcare your
at your
doorstep with doorstep our
with our
all-new direct all-new to patient
direct to patient
Discover the future of
healthcare at your
doorstep with our
all-new direct to patient
kit delivery for kit the delivery IBDoc for the IBDoc Elevate ®
Your
Elevate Your kit delivery for the IBDoc ®
Elevate Yo
ctin self-testing calprotectin system. self-testing This solution
system. This solution calprotectin Healthcare self-testing Approach
Healthcare system. Approach This solution calprotectin Healthcar
rs both empowers patients both and patients clinicians, and redefining
clinicians, redefining empowers with Seamless both with patients Remote
Seamless and clinicians, Remote redefining empowers with Seam b
agement.
IBD management.
IBD Testing management. using Testing the BUHLMANN using the IBDoc BUHLMANN :
IBDoc ® : IBD Testing manage us
ves requirement f
Removes for requirement administrative for logistics
administrative logistics f fRemoves Excellent requirement correlation f Excellent for with administrative correlation laboratory
with logistics
laboratory
f fRemoves Excellen r
ding kits to in sending patients
kits to patients
in tests sending and kits endoscopic to tests patients
and findings
endoscopic findings
in sending tests an
ves shelf f life Improves and stock shelf level life and management
stock level management f fImproves Swift quantitative shelf flife Swift and testing, quantitative stock level giving management
testing, results
giving results
f fImproves Swift qu s
ed deliveries:
f
Tracked deliveries:
f Tracked the same deliveries: day for the the same clinical day team for the and clinical the patient
team and the patient f Tracked the sam de
eekly reports Z
Weekly of dispatch reports requests of dispatch available
requests availablef Z Minimized Weekly reports pre-analytical f Minimized of dispatch errors pre-analytical requests thanks available to errors simple
thanks to simple fZ
Minimiz Weekl
sample preparation
sample preparation
sample
illing only Zwhen Billing kits are only sent when out
kits are sent out
Z Billing only when kits are sent out
Z Billing
f Individualised f kit Individualised containing everything kit containing the patient everything the patient f Individu
le delivery f
Flexible options delivery (number options of kits (number and location)
of kits and location) f Flexible
needs
delivery
for a single
options needs test
for
(number a single
of test
kits and location) f Flexible
needs
de
f
ers in As innovative pioneers in healthcare
innovative healthcare As pioneers in innovative healthcare
As pioneers i
, we're solutions, proud to we're announce proud to our
announce our solutions, we're proud to announce our
solutions, we
approach enhanced to approach home testing to home logistics.
testing logistics. Elevate enhanced your Elevate approach IBD management your to home IBD management testing today logistics.
today Elevate enhanced your ap IB
boratories Alpha Laboratories now presents now the
presents the Reach Alpha out Laboratories Reach us at out digestivedx@alphalabs.co.uk
now to us presents at the
Reach Alpha out Labora to us
ity for opportunity direct IBDoc for ® direct kit delivery,
IBDoc ® kit delivery, opportunity for direct IBDoc ® kit delivery,
opportunity
he patients’ right to the homes.
patients’ homes.
right to the patients’ homes.
right to the p
3000 02380 • sales@alphalabs.co.uk 483000 • sales@alphalabs.co.uk • www.alphalabs.co.uk
• www.alphalabs.co.uk
02380 483000 • sales@alphalabs.co.uk • www.alphalabs.co.uk 02380 48300

NEWS
Inflammatory bowel disease
treatments reach inflection
point requiring active
comparators, says GlobalData
At Digestive Disease Week (DDW)
2023, a comment was made following a
presentation discussing the preliminary
induction findings from GlobalData, a
leading data and analytics company.
The attendant continued by pointing out that
GUS was shown to only effect remission in less
than a quarter of the treated patients (22.5%),
with a moderate benefit over placebo of only
approximately 12%. The commenter concluded
the argument with the observation that GUS and
many other inflammatory bowel disease (IBD)
therapies do not meet the historical therapeutic
standards, referencing a recent meta-analysis
study that showed that treatments generally
achieve a 20% delta over placebo.
Adeleke Badejo, Senior Analyst – Immunology
at GlobalData, comments: “At the crux of this
line of thought is a lack of evidence to support the
market narrative and messaging of high-quality
current and upcoming IBD therapies, and a need
for better data.”
Observed from recent interviews of key opinion
leaders (KOLs) within IBD conducted by
GlobalData, the unmet need for more evidence
to define the most efficacious therapy in the
field has been echoed repeatedly. One such
thought leader acknowledged the current status
quo with companies being able to “get away, so
to speak, in the IBD field with these placebocontrolled
trials”.
Adding that the sole use of placebo is not the
norm with other indications. “I think you see more
comparative effectiveness trials in some of the
other fields, certainly in oncology… it’s always
the standard of care versus the new thing”.
Addressing this situation, not only improves the
quality of care for the IBD patient population,
but it also would benefit companies in a quickly
evolving and expanding market.
Badejo continues: “The significance of
addressing this unmet need is of increased
importance in light of recent bets within IBD and
immunology through mergers and acquisitions,
such as the purchase of Prometheus
Biosciences by Dice Therapeutics.”
In addition to the effect these strategic
transactions will have on the market in the coming
years, long-established agents such as Humira
and Stelara are transitioning to legacy assets,
providing the opportunity for the next generation
of treatments to capture significant market share.
The current situation would be best addressed
through clinical asset evaluation through trials
with active comparators, but of the eight latestage
pipeline agents at the beginning of this
year, only Lilly’s mirikizumab and AstraZeneca’s
brazikumab were being evaluated against
active comparators (ustekinumab and
adalimumab respectively), with the former
program ending following assessment of the
competitive landscape.
Badejo concludes: “The apparent risk with
higher probability of failure associated with
incorporating active comparators during therapy
development is known, but the benefit in
establishing confidence with decision makers
should not be overlooked.”
GASTROENTEROLOGY TODAY – AUTUMN 2023
26

COMPANY NEWS
A New Portal To Ef-FITciency:
Introducing The
Alpha Portal (TAP) by Alpha
Laboratories
The Faecal Immunochemical Test (FIT)
has revolutionised the colorectal cancer
referral pathway with its quick and
user-friendly nature, making it an easily
integrated test for efficient patient triaging.
However, the valuable benefits of FIT
have brought forth logistical challenges,
primarily concerning sample collection
kit distribution to healthcare providers
and patients. The increasing demand for
this essential test is rapidly outpacing the
current capacity.
To tackle these challenges head-on, Alpha
Laboratories has collaborated with FIT users
to introduce the Alpha Portal (TAP), marking
the next phase in FIT evolution. TAP is a
cutting-edge solution designed to streamline
and manage the logistics associated with
the Faecal Immunochemical Test, providing
a scalable and efficient system to meet
the surging demand. Already proving its
effectiveness, Southmead Hospital in Bristol
has experienced significant improvements in
its FIT service following the implementation
of TAP.
Key features of the Alpha Portal include:
FIT-KIT Stock Management: Offering a
snapshot of FIT-KIT stock levels, lot and
expiry dates, and real-time tracking to ensure
a continuous and seamless supply.
Print-Ready Documents: Providing
healthcare providers with easily accessible
and print-ready documents detailing kit
components and product descriptions.
Traceable Ordering System: Implementing
a sophisticated ordering system to deliver
FIT-KITs to any location in the UK, ensuring
prompt and reliable distribution.
Order Reports: Generating comprehensive
order reports that highlight demand at each
site and ordering frequency, allowing for
better inventory management.
The Alpha Portal has been met with
enthusiasm and praise from various
healthcare facilities across the UK,
significantly reducing unnecessary workload
and enhancing the scalability of the FIT
service. As Alpha Laboratories remains
committed to delivering top-notch solutions, it
has exciting plans for additional offerings from
TAP in the near future.
In conclusion, the Alpha Portal (TAP) is
a game-changing tool for managing the
logistical challenges associated with the
Faecal Immunochemical Test (FIT). It
provides an efficient and reliable means of
tracking, ordering, and distributing FIT-KIT
components, enabling healthcare providers
to meet the soaring demand for this crucial
test. By adopting TAP, healthcare facilities
can optimize their FIT services and focus on
providing timely and effective care to patients.
Please visit www.faecal-immunochemicaltest.co.uk/TAP
for further information or
contact Alpha Laboratories on 0800 38 77 32
or email marketing@alphalabs.co.uk
Microbiome characterisation
ensures success in faecal
microbiota transplantation
Graham Johnson, Managing Director,
BIOHIT Healthcare.
Faecal microbiota transplantation (FMT)
is becoming a more widespread treatment
for dysbiosis-associated conditions, in
particular, for gastrointestinal disorders,
and its use was further endorsed
recently when, in 2022, the National
Institute for Health and Care Excellence
(NICE) approved it for treating recurrent
Clostridium difficile infections.[1]
However, several randomized controlled
trials investigating FMT in irritable bowel
syndrome (IBS) patients have revealed
huge variability in treatment response.
[2] These contradictory findings may be
attributable to a lack of standardisation
in various aspects of the trial protocol
design, one of which is donor selection
criteria.[3] At the same time, there has
been a rising tendency to recruit ‘superdonors’
– favourable both in terms
of their microbial diversity and stool
composition – with the aim of ensuring
positive outcomes for recipient patients.
[4, 5] The gut microbiota of these donors
is currently not always characterised, but
some advocates of FMT are beginning to
suggest that this may be more valuable
than simple clinical screening when it
comes to matching recipients to donors,
especially with the innovative diagnostic
tools that are now available.[6] Microbial
profiling undoubtedly provides key
information, such as the abundance and
diversity of bacteria in the gut – as well as
a measure of dysbiosis in patients – and
applying this approach across the board
as a measure of standardisation could
help to refine therapeutic FMT strategies
and lead to more consistent study results
with favourable patient outcomes.[7]
Purposeful protocol design
This is certainly the strategy chosen by Magdy
El-Salhy, Professor of Gastroenterology
and Hepatology at the University of Bergen,
whose research team recently conducted a
clinical trial to determine the efficacy of FMT
for IBS patients.[8] The study found that FMT
is an effective therapy for IBS, with up to 89.1
% of patients responding to treatment, and
around half of all patients experiencing clinical
improvements in abdominal symptoms,
fatigue and quality of life. However, Magdy is
convinced that protocol design was key to
ensuring the validity of the study results. There
were five important factors: the super-donors
were screened against set criteria; there
was frequent faecal analysis of the donor to
monitor microbiome stability; the fresh donor
faeces were immediately frozen; the sample
was mixed manually prior to administration;
and the donor material was administered
by gastroscope directly into the recipient’s
duodenum.
The right tool for the job
On top of this, the GA-map ® Dysbiosis
Test (GA-map ® Test) – a gut microbiota
DNA-based platform that identifies and
characterises dysbiosis – was used
throughout the trial, as Magdy explained:
“The GA map ® Test was fundamental to the
analytical element of our trial; we used it to
profile the faecal samples from the donor and
to evaluate the intestinal bacterial profiles of
patients following transplantation.” GA-map ®
Test assigns each sample with an index that
ranges from 1 for ‘normobiosis’ to any score
greater than 2 to represent an increasing
degree of dysbiosis. Samples are then
cross-indexed with an additional value that
represents the abundance of present species
compared to the reference population.
Indexing in this manner refines the definition
of dysbiosis and multiple FMT studies have
correlated the GA-map ® Test index with
effectiveness of therapeutic intervention.[9-12]
Standardisation for success
The trial protocol included faecal analysis of
the super-donor at the start of the study to
ensure that they had normal gut microbiota,
and then at three monthly intervals
throughout the year to confirm stability of
their microbiome. Christina Casèn, Senior
Vice President, Clinical and Medical Affairs at
GASTROENTEROLOGY TODAY – AUTUMN 2023
27

COMPANY NEWS
GASTROENTEROLOGY TODAY – AUTUMN 2023
Genetic Analysis AS, said: “A standardised
and validated test that could be conducted
in situ was vital for this study as it involved
repeated sampling and measurements of
the donor. Performing analyses with the
GA-map ® Test allowed the trial clinicians to
compare results from different time periods
instantaneously and evaluate FMT efficacy
on site.”
Characterisation to further understanding
The study conducted by Magdy and his
team confirmed that the outcome of FMT
in IBS patients is donor dependent, and
demonstrated that standardisation of key
aspects of the trial protocol is critical. A donor
needs to be well defined with both a normal
dysbiosis index and a favourable specific
microbial signature, and using dysbiosis
testing platforms for characterisation can
reduce variability in clinical response and
ultimately ensure success of the FMT method.
When clinicians are able to perform DNAbased
faecal analysis themselves during
trials – without needing to send samples to an
external sequencing laboratory – they benefit
from instantaneous information that guides
FMT as an effective therapeutic intervention.
References
[1] NICE recommends transplant with
good bacteria taken from poo to resolve
recurrent Clostridium difficile infections |
News | News | NICE, https://www.nice.
org.uk/news/nice-recommends-faecalmicrobiota-transplant-for-recurrentclostridioides-difficile-infection
(accessed
16 January 2023).
[2] Cammarota G, Ianiro G, Tilg H, et al.
European consensus conference on
faecal microbiota transplantation in
clinical practice. Gut 2017; 66: 569–580.
[3] El-Salhy M, Hausken T, Hatlebakk
JG. Current status of fecal microbiota
transplantation for irritable bowel
syndrome. Neurogastroenterology
and Motility; 33. Epub ahead of print
1 November 2021. DOI: 10.1111/
NMO.14157.
[4] Koren O, Fiorucci S, O’sullivan JM,
et al. The Super-Donor Phenomenon
in Fecal Microbiota Transplantation.
Frontiers in Cellular and Infection
Microbiology | www.frontiersin.org; 1.
Epub ahead of print 2019. DOI: 10.3389/
fcimb.2019.00002.
[5] Moayyedi P, Surette MG, Kim PT, et
al. Fecal Microbiota Transplantation
Induces Remission in Patients With
Active Ulcerative Colitis in a Randomized
Controlled Trial. Gastroenterology 2015;
149: 102-109.e6.
[6] Allegretti JR, Mullish BH, Kelly C, et
al. The evolution of the use of faecal
microbiota transplantation and emerging
therapeutic indications. The Lancet 2019;
394: 420–431.
[7] Ianiro G, Puncochár M, Karcher N, et
al. Variability of strain engraftment and
predictability of microbiome composition
after fecal microbiota transplantation
across different diseases. Nature
Medicine 2022 28:9 2022; 28: 1913–
1923.
[8] El-Salhy M, Gunnar Hatlebakk J,
Kristoffersen AB, et al. Gut microbiota
Efficacy of faecal microbiota
transplantation for patients with irritable
bowel syndrome in a randomised,
double-blind, placebo-controlled study.
Gut 2020; 69: 859–867.
[9] Wei S, Bahl MI, Dahl Baunwall SM, et
al. Determining Gut Microbial Dysbiosis:
a Review of Applied Indexes for
Assessment of Intestinal Microbiota
Imbalances. Epub ahead of print 2021.
DOI: 10.1128/AEM.00395-21.
[10] El-Salhy M, Hausken T, Hatlebakk JG.
Increasing the Dose and/or Repeating
Faecal Microbiota Transplantation (FMT)
Increases the Response in Patients with
Irritable Bowel Syndrome (IBS). DOI:
10.3390/nu11061415.
[11] Mazzawi T, Lied GA, Sangnes DA,
et al. The kinetics of gut microbial
community composition in patients with
irritable bowel syndrome following fecal
microbiota transplantation. PLoS One
2018; 13: e0194904.
[12] El-Salhy M, Hatlebakk JG, Gilja OH,
et al. Efficacy of faecal microbiota
transplantation for patients with irritable
bowel syndrome in a randomised,
double-blind, placebo-controlled study.
Gut 2020; 69: 859–867.
Biography
Professor Magdy El-Salhy, BSc, MSc,
MD, PhD is a professor emeritus in the
Department of Clinical Medicine at the
University of Bergen, where he leads the
Neurogastroenterology Section, as well as
being a consultant gastroenterologist in the
Department of Gastroenterology at the Stord
Helse Fonna Hospital. Professor El-Salhy has
investigated the gut neuroendocrine system
(NES) and its role in different gastrointestinal
diseases/disorders for almost 40 years,
authoring more than 280 publications,
and is an editorial board member for nine
international journals. His research during the
last 15 years has been devoted to improving
our understanding of the pathophysiology of
IBS, and the development of new methods
for its diagnosis. Professor El-Salhy has been
awarded several prestigious prizes in Egypt,
Sweden and the Republic of Bashkortostan,
as well as from United European
Gastroenterology, the European Society of
Neurogastroenterology, and Motility, and The
Rome Foundation.
The 18th Dr Falk Pharma/
Guts UK Awards:
Recognising Dedication,
Enthusiasm & Commitment
in Digestive and Metabolic
Disease
‘The future of GI & Hepatology medicine
& healthcare is in safe hands.’
A trainee doctor researching the role of
the gut microbiome within the potentially
fatal liver condition biliary atresia, a medical
student examining the safety and efficacy of
a capsule form of oesophageal investigation,
a dietitian who instigated a system to provide
patients with oesophago-gastric cancers,
early contact with specialist dietitians, and
a pharmacist who designed and developed
pharmacist-led Inflammatory Bowel Disease
(IBD) clinics to review and assess patients on
biologics.
These are just a few of the talented winners of
the 2023 Dr Falk Pharma UK/Guts UK Charity
Awards, who received their prizes during a
dinner on Tuesday June 20th at the British
Society of Gastroenterology (BSG) Annual
Meeting in Liverpool.
Now in its 18th year, celebrating research and
patient care improvement projects carried out
by medical students, junior doctors, specialist
nurses and dietitians, for the first time a
pharmacist award (with two winners) has
been added to the award’s roll call of honour.
With the aim of recognising and further
supporting the increasingly important role of
28

COMPANY NEWS
us with the privilege of learning about
the excellent standards of research and
patient improvement innovations carried
out by young doctors and other dedicated
healthcare professionals within the field of
gastroenterology and hepatology - and 2023
has been no exception.
‘We are delighted too, that this year for the
very first time, our rostrum of winners includes
pharmacists, who play such an important role
in the care of patients with GI or liver diseases.
‘Every one of our winners has shown
passion for their projects, plus the dedication
needed to complete them to an extremely
high standard, often alongside working or
studying full time. They really are the best of
our profession and provide evidence that the
future of GI and Hepatology medicine and
pharmacists within the integrated healthcare
teams, the applications were open to all
pharmacists working in primary or secondary
care and other areas where service redesign
or any project has had a positive impact on
patient outcomes.
The worthy winners were presented with
their awards and prizes by the President
of the BSG, Professor Andrew Veitch and
the Medical Director of Dr Falk Pharma UK,
Dr Riadh Jazwari. Also at the dinner was
the CEO of Guts UK, MS Julie Harrington,
the Managing Director of Dr Falk Pharma
UK, Mr Tony McFadyen, as well as several
internationally renowned members of the
gastroenterology & hepatology community.
Dr Victoria King, Chair of Trustees at Guts UK
comments: ‘For almost two decades, Dr Falk
Pharma UK and Guts UK Charity have been
working hard to maintain the supply of bright,
enquiring minds within gastroenterology,
hepatology and pancreatology.
‘Each year, we come together to recognise
the dedication, enthusiasm and commitment
shown from medical students, doctors,
nurses and dietitians. For the first time in
2023, we are delighted to introduce a prize for
pharmacists too. To the winners, our future
Guardians of the Gut – congratulations!’
Medical student Ms Ho Kiu Giselle Ngan
received the Dr Falk Medical Student Essay
Prize for her project entitled A Genomewide
Association Study of Non-alcoholic
Liver Disease in India. Ms Ngan undertook
this research project whilst intercalating for
an iBSc Sciences with Clinical Sciences at
University College London Medical School.
Ms Ngan notes: ‘It is a great honour for me
to receive the Dr Falk Essay Prize. I aspire to
further explore the field of Hepatology and
translational medicine in order to promote
personalised medicine and benefit a wider
population. This award provides me with great
encouragement to pursue a medical career
involving clinical research to help progress
medicine.’
Advance Nurse Practitioner Ms Pearl Avery
has won the Nurse Recognition Award for
the evaluation of her novel role managing
Inflammatory Bowel Disease (IBD) patients in
a primary care setting, reducing unnecessary
referrals to secondary care and reduction
of patients living with long term unresolved
symptoms.
Ms Avery explains: ‘I believe that my project
has provided real benefit to patients and
the GP practice, and I am passionate about
taking this out to GP networks to see if this
model may be adopted by other practices.
‘Winning this award has provided me with
the funding to support this idea, giving me
capacity to work on the analysis which will
allow me to clearly demonstrate the cost
benefit and how the model can fit into primary
care.’
Dr Jazwari comments: ‘Each year, the Dr
Falk Pharma/Guts UK Awards provide
healthcare is in safe hands.’
Brand New Online
Experience from Alpha
Laboratories
New Website for Diagnostic and
Laboratory Solutions.
Alpha Laboratories Ltd. is proud to unveil
its new website, that has been designed to
offer scientists and clinicians easier access to
a wealth of information, across its laboratory
and diagnostics supplies, services and
solutions. Reflecting the company’s growth,
through its customer-focused approach,
it presents an application driven platform,
tailored to meet the needs of both new and
existing customers.
The new website provides a modern, userfriendly
interface that is easy to navigate.
It features a practical search function with
intelligent filtering capabilities that enables
customers to conveniently browse through
both product listings and supplementary
information page options. This helps
customers find what they need easily and
quickly, whether they are planning an
immediate purchase through the efficient
e-commerce platform or are researching
options to be ordered through their own
internal procurement system.
“Our priority has always been to provide the
best possible products and services to our
customers and our new website is just one of
the many ways we continue to support that,”
GASTROENTEROLOGY TODAY – AUTUMN 2023
29

COMPANY NEWS
GASTROENTEROLOGY TODAY – AUTUMN 2023
says Carole Staniford, Marketing Director.
“We’ve worked hard to create a website that
reflects our commitment to our customers,
and we believe that our new site will make
it easier for them to do business with us,
from direct online transactions to working
in partnership to create bespoke customer
solutions.”
The website features an updated design that
is compatible with all devices and screen
sizes, ensuring that users can access the site
on the go, and from any device. Customers
can easily search for products by product
code, key words, category or applications,
view product specifications, access literature,
videos etc. and even place orders directly
online. For those who need assistance or
have specific queries, the new website also
includes a dedicated customer support
section where they can get in touch with
Alpha Laboratories’ product experts.
Alpha Laboratories Ltd.’s new website
reinforces the company’s position as a topquality
supplier in the market. The website
is live now and ready to explore. For further
information or enquiries, please visit
www.alphalabs.co.uk
Introducing therapeutic
drug monitoring into routine
clinical practice
Dr Christian Selinger, Consultant
Gastroenterologist, Leeds Teaching
Hospitals NHS Trust.
The treatment of inflammatory bowel
disease (IBD) has developed significantly
since the widespread introduction of
biopharmaceuticals. Common biologics
include the TNF-α inhibitors infliximab
(IFX) and adalimumab (ADM), with
vedolizumab and ustekinumab also rapidly
becoming more popular.1 Up to 85 per
cent of patients with IBD have a clinical
response to TNF-α inhibitors, but many
show drug-unresponsiveness either at
instigation of therapy or later on during
the first year of treatment.2 This is often
caused by the development of anti-drug
antibodies (ADAs), which lead to lower
drug trough levels in the bloodstream,
presenting a considerable challenge in
determining the correct course of action
for effective treatment. Therapeutic drug
monitoring (TDM) of trough levels and
ADAs is emerging as a useful tool for
detecting drug unresponsiveness early
on but, despite positive reports of its
reactive use in secondary loss of response
situations,2 uptake has so far been low,
and routine clinical practice for proactive
TDM remains poorly defined. This may
be due, at least in part, to the poor
availability of high sensitivity assays for
trough levels and ADAs, a lack of standard
measurement thresholds, and the potential
expenses incurred by additional testing.2
Pioneers of TDM in gastroenterology
The Leeds Teaching Hospitals NHS Trust
comprises a total of eight hospitals across
West Yorkshire, and provides acute, elective,
secondary and tertiary IBD care to around
4,000 patients. The trust’s gastrointestinal
services are centred at St James’s University
Hospital in Leeds, and are supported by two
additional outpatient endoscopy clinics. The
department applies both medical and surgical
approaches to the prevention, diagnosis and
management of gastrointestinal diseases, and
aims to provide a patient-focussed approach
to treatment.
The trust currently performs TDM of IFX
treatment at 12 and 52 weeks for patients
receiving IV infusions, combining clinical
assessment, medical history, blood
biomarkers – trough and ADA levels – and
imaging to form a complete picture of each
patient’s clinical status. The service uses
the IDKmonitor ® Infliximab Total Anti-drug
Antibody ELISA (BIOHIT HealthCare) to
detect bound and free ADAs in the patient’s
bloodstream. This highly sensitive drugtolerant
assay is particularly useful in
identifying patients with low-titre ADAs, and
supports both the proactive and reactive
investigation of primary non-response and
secondary loss of response to IFX.
This assay has enabled the early detection
of elevated ADA levels in IBD patients
receiving IFX, aiding doctors in making
treatment decisions that may prevent future
lack of response, such as introducing an
immunomodulator or combination therapy, or
optimising dosage to avoid undertreatment.
This pre-emptive TDM approach has allowed
for more effective disease control, leading
to better long-term outcomes for patients
on IFX, and has also helped to reduce
the unnecessary use of drugs, which may
contribute to overall cost savings for the NHS
in the long run.
In addition, the trust sends samples to an
external laboratory for analysis with the
IDKmonitor ® Adalimumab Total Anti-drug
Antibody ELISA, enabling it to perform
reactive TDM for any patient experiencing
loss of response to ADM. Clinicians have
noticed benefits from this analysis, indicating
that proactive monitoring of ADM may also
be advantageous in the future. This approach
could bring other long-lasting benefits to both
the healthcare system and individual patients,
as early observations suggest that therapy
optimisation through TDM has helped to
avoid the need for costly and invasive repeat
imaging procedures, such as colonoscopies
or sigmoidoscopies.
An evidence-based approach to disease
management
TDM performed at the Leeds Teaching
Hospitals NHS Trust has shown much
potential for supporting clinicians in safely
altering TNF-α inhibitor treatment in
individuals showing suboptimal responses,
without negatively affecting patient outcomes
or incurring additional expenses.1,2 Evidence
is also mounting nationally that suggests TDM
for IFX and ADM should be an integral part of
IBD services, although more extensive and
long-term studies are needed to strengthen
this. It will also be important to examine the
role of TDM for subcutaneously delivered IFX
and for other biologics – such as vedolizumab
and ustekinumab – in the coming years,
as there is so far very little data to suggest
whether monitoring would enhance the
outcomes of patients in these care pathways.
Unfortunately, TDM is still not sufficiently
high up on the agenda for many NHS trusts
due to time and financial pressures, and the
case for proactive TDM is not yet compelling
enough to overcome these major barriers and
convince decision makers that widespread
implementation would be a worthwhile
30

COMPANY NEWS
endeavour. However, it is clear that getting the
treatment right from the beginning leads to
better long-term outcomes for IBD patients,
and studies are revealing that bringing TDM
for a range of IBD biologics into routine
practice may have a huge role to play in
supporting this.
References
1. Sagar, R. et al. 2021. Infliximab
Therapeutic Drug Monitoring in
Inflammatory Bowel Disease Virtual
Biologics Clinic Leads to Durable Clinical
Results. Inflamm Intest Dis. 6:132–139,
DOI: 10.1159/000515593.
2. Selinger CP, Lenti M v., Clark T, et al.
2017. Infliximab Therapeutic Drug
Monitoring Changes Clinical Decisions in
a Virtual Biologics Clinic for Inflammatory
Bowel Disease. Inflamm Bowel Dis.
23(12):2083-2088.
Tillotts Pharma and TVM
Capital Life Science
Announce Formation of
Mage Biologics to Develop
Innovative Oral Antibody
Therapy for Ulcerative Colitis
Mage Biologics to develop a monoclonal
antibody targeting ulcerative colitis
early-stage or project-focused company (PFC)
investment for TVM LSI II.
Mage Biologics plans to advance to clinical
proof of concept a novel, orally administered,
humanized monoclonal antibody (mAb)
bioengineered for optimal potency and tissue
penetration. The mAb has been developed
by Tillotts and originated from a discovery
collaboration with Swiss biotech company
Numab Therapeutics. Utilizing Tillotts’
innovative sustained release approach, the
antibody is designed to enable release of the
drug in the appropriate area of the intestinal
tract at a predetermined rate to address
inflammation locally and optimally. Initially, the
drug will be developed for the treatment of
ulcerative colitis. Manufacturing of clinicalgrade
material is planned to start in 2023, with
the goal of filing a clinical trial application in
2024.
Thomas A. Tóth von Kiskér, CEO and
Board Director of Tillotts, commented:
“We are excited to team up with TVM Capital
Life Science to advance this oral antibody
in ulcerative colitis, a lifelong disease
profoundly impacting the patients’ quality of
life. The collaboration with TVM underpins
Tillotts’ leading role in developing and
condition. I look forward to advancing our
antibody to clinical proof of concept.”
About ulcerative colitis
Ulcerative colitis (UC) is an inflammatory
bowel disease (IBD) that impacts millions of
people worldwide. Ulcerative colitis affects
the innermost lining of the colon and the
rectum, causing inflammation and ulcers in
the digestive tract. In most people, symptoms
usually develop over time, taking a relapsingremitting
course, which means that periods of
flare-ups are followed by periods of remission.
This can be draining and, in some cases,
lead to life-threatening complications. While
there is no known cure, current treatments
aim to reduce signs and symptoms of the
disease and bring remission. Over the last
decade, biologics have gained an important
place in the treatment of ulcerative colitis,
with several monoclonal antibodies available
as subcutaneous or intravenous therapies
approved for use in UC. Unfortunately,
a substantial proportion of patients do
not respond, lose response, or develop
intolerance to currently marketed products,
leading to a substantial unmet medical need
for safer, effective, and more convenient
therapeutic options.
Novel antibody specifically designed
for oral administration utilizes Tillotts
Pharma’s sustained release approach to
ensure optimal and local treatment
Mage Biologics is the 10th earlystage
or project focused company
(PFC) investment for TVM Life Science
Innovation II Fund.
Montreal, Canada / Munich, Germany /
Rheinfelden, Switzerland – 20 July 2023
– Life Science Newswire – TVM Capital Life
Science (“TVM”), a leading international
venture capital firm focused on investments
in life sciences innovation, together with
specialty pharma company, Tillotts Pharma
(“Tillotts”), today announced that the
companies will jointly invest up to USD
28 million in the newly formed U.S.-based
biotechnology company, Mage Biologics Inc.
(“Mage Bio”). TVM will invest with its fund TVM
Life Science Innovation
II SCSp (“TVM LSI II”) and will provide
strategic advice to Mage Bio, with Dr. Sascha
Berger, General Partner, joining the Board of
Directors and Dr. Ivan Shaw, Principal, serving
as a Board Observer. Mage Bio is the 10th
commercializing innovative products in the
gastrointestinal field.”
“TVM Capital Life Science is proud to have
enabled the creation of Mage Biologics.
This investment is again a testament to our
strong international network and builds
on our successful single asset focus for
innovative preclinical therapeutic agents,”
said Sascha Berger, General Partner of
TVM Capital Life Science and Member
of the Board of Mage Biologics. “We are
pleased to collaborate with the experienced
management team of Johannes Spleiss and
Chantal Miklosi, who will act as CEO and
CFO, respectively, for Mage Biologics.”
Johannes Spleiss, Head of Scientific
Affairs at Tillotts and CEO of Mage
Biologics, added: “We are taking a new and
potentially disruptive approach to overcome
the challenges with traditional ulcerative colitis
treatments with this oral antibody. Developing
more efficacious therapies with a greater
likelihood of success and less systemic side
effects is an important step in continuing to
innovate for the many patients living with this
About the project-focused company (PFC)
For its PFC investments, TVM has a unique
arrangement with Eli Lilly and Company
(“Lilly”), which is a limited partner in TVM LSI
II and the earlier fund TVM LSI I, under which
TVM and its PFCs have the option to engage
Chorus, a full-service autonomous research
and development unit within Lilly, to assist the
PFC by implementing a lean and focused drug
development plan, resulting in high-quality
data packages to help determine proof of
concept.
About Tillotts Pharma
Tillotts Pharma AG, part of the Japanese Zeria
Group, is a fast-growing specialty pharma
company with close to 400 employees
in Switzerland and abroad. Tillotts is
dedicated to the development, acquisition
and commercialization of innovative
pharmaceutical products for the digestive
system. Tillotts successfully markets its
own products for the treatment of IBD and
Clostridioides difficile infection (CDI) as well as
in-licensed products in around 65 countries
through its affiliates within Europe and a
network of partners throughout the world.
GASTROENTEROLOGY TODAY – AUTUMN 2023
31

Helicobacter Test INFAI ®
One of the most used
13
C-urea breath tests for the diagnosis
of Hp-infections worldwide
• New line of INFAI packaging and serialization according the EU’s Falsified Medicines Directive
• More than 7.0 million Helicobacter Test INFAI performed worldwide
• Registered in more than 40 countries worldwide
• First approved Hp test for children from the ages of 3 to 11
• Modified Hp test for patients taking PPIs (REFEX)
• Modified Hp test for patients with atrophic gastritis
• Cost-effective CliniPac Basic for hospital and GPs use
INFAI UK Ltd
Innovation Centre, York Science Park
University Road, Heslington
York YO10 5DG UK
Phone: +44 1904 435 228
Fax: +44 1904 435 229
E-Mail: mail@infai.co.uk
Web: www.infai1.com