BSRBR|Newsletter - The British Society for Rheumatology

BSRBR|Newsletter 

The British Society for 

Rheumatology 

Biologics Register 

The Newsletter of the British Society for Rheumatology Biologics Register 

October 2009 

Editorial 

Report on the BSR Biologics 

Register Committee 

I am happy to confirm that a major step in the direction of establishing an 

ankylosing spondylitis register has been achieved in line with Professor Barry 

Bresnihan’s proposal that BSRBR should expand to include an assessment of the 

effects of biological agents in other diseases. With help from National Ankylosing 

Spondylitis Society (NASS), the pharmaceutical company Wyeth and funds from 

BSR itself, a sum of £30,000 has been raised. This enabled us to appoint 

Dr Lorna Layward to the role of Register Development Officer. 

The main elements of Lorna’s role will be to: 

• seek an agreement about the principle questions that an 

ankylosing spondylitis register would seek to answer; 

• develop the tendering process for a centre to run the 

register; 

• approach the clinical trials network to obtain prior support 

for this register on the basis of the clinical questions being 

addressed; and finally (and rather importantly!) 

• engage the pharmaceutical industry and any other parties 

who might be interested in actually funding such a register 

for a minimum of five years. 

If you would like to input your views on any of these issues in setting up the AS register 

please email Lorna on: llayward@rheumatology.org.uk 

I would also like to take this opportunity of thanking Barry for the huge amount of work 

he put in to his assessment of the register, unfortunately Barry has fallen ill and we 

would therefore like to wish him the very best. 

David A Isenberg MD FRCP, ARC Diamond Jubilee Professor of 

Rheumatology at University College London 

Working with the arc 

Epidemiology unit in Manchester 

BSRBR has been a tremendous success, quite rightly described by 

David Isenberg as the “jewel in the crown of BSR”. The triumphs are well 

publicised in a host of highly informative papers published in the world’s 

leading rheumatology journals. However, people may not be aware that the 

BSRBR’s wealth of data can be accessed by all. Here Dr Chris Deighton 

explains how, with the help of the arc Epidemiology Unit in Manchester, 

analysis from the BSRBR has helped in negotiations with NICE. 

We all express concerns about current NICE restrictions on access to anti-TNF 

for RA patients, but without the help of BSRBR we would not even have the 

current availability of these drugs in the NHS. Let me share with you some of the 

help that Manchester unit have provided for those of us who negotiate with NICE 

both in the past and in ongoing appraisals. 

From the first negotiations with NICE on access to anti-TNF for RA, we struggled 

to demonstrate that these drugs are cost-effective according to NICE health 

Continues on page 2 . . . 

BSR Biologics 

Register and 

what is does 

The British Society for Rheumatology Biologics 

Register (BSRBR) tracks the progress of 

patients with severe rheumatoid arthritis (RA) 

who are receiving biologic agents, including 

rituximab, monitoring the safety and 

effectiveness of these treatments over 

the long term. 

Patients are registered and followed up until the 

end of the study (2013 for the anti-TNF cohort 

and later for the rituximab cohort) to assess their 

response to treatment and to capture detailed 

information about serious adverse events. Patients 

are flagged with the NHS Information Centre, 

which notifies BSRBR of any cases of cancer or 

deaths and their causes. Data is also collected 

for patients with similar disease activity who are 

receiving conventional disease modifying drugs 

(DMARDs). 

BSRBR is supported by a team of 14 people, 

based at the arc Epidemiology Unit at the 

University of Manchester, directed by the principal 

investigators, Professor Deborah Symmons and 

Dr Kimme Hyrich. They provide an extensive range 

of services including local investigator liaison, data 

management, pharmacovigilance, analyses and 

reports. 

BSR is leading this unique research collaboration 

between a medical professional society and the 

pharmaceutical industry, with participation from all 

consultant rheumatologists, supported by allied 

health professionals, across the UK. 

The project is coordinated through a BSR 

Biologics Register Steering Committee, 

chaired by Professor David Isenberg and 

Biologics Register Coordinator, Nia Taylor. 

1


Continued from page 1 . . . 

economic analyses. This applies to first-line use of the drugs and even more so 

to sequential use following the failure of a first anti-TNF. 

BSRBR has produced a wealth of observational data on real-life use of anti-TNF 

in the NHS. BSRBR patients tend to have long disease duration with 

well-established disease, failing on many conventional DMARDs (usually many 

more than the two required by NICE). As such, they may not be ideal to study 

efficacy. NICE health economic analyses are driven by the change in Health 

Assessment Questionnaire (HAQ), and in patients with established disease, this 

is governed by factors other than disease activity, such as damage to joints. 

Therefore the ability of anti-TNF to influence the HAQ in the BSRBR population 

is much less than in patients with a more recent onset of RA. We have used this 

as an argument to show that as time has gone by, rheumatologists are using 

biological drugs in patients with earlier disease that is proving resistant to 

conventional DMARDs, and where data shows that these patients will respond 

better than the BSRBR patients. 

Colleagues at the arc Epidemiology Unit in Manchester have performed helpful 

analyses, sometimes at short notice with tight NICE timetables with occasional 

late-night telephone calls before Appraisal Committee meetings. With health 

economists in Sheffield, they have performed analyses with change in DAS28 as 

the driver of the model, suggesting that anti-TNF was cost-effective in treating 

RA, despite the limitations of the BSRBR data. This alternative approach to a 

health economic analysis, as well as other evidence, was instrumental in 

producing sufficient doubt in the veracity of the original NICE health economic 

models to allow access to a first anti-TNF. 

University of 

Manchester update 

Cohort recruitment update 

BSRBR recruitment to the anti-TNF and the comparison 

cohort for patients with RA is complete, with an overall 

total of over 16,000 patients. More importantly, we are 

extending the follow-up and will continue to collect data 

from you and the UK national registers for cancer and 

deaths for all of these patients until at least 

September 2013. 

Rituximab (RTX) recruitment is increasing and by end of 

August we had registered 442 people. We aim to recruit 

1,100 RTX treated patients to allow us to thoroughly 

analyse the risk of serious infection so please continue 

to register any new rituximab patients with us. Other cohorts 

that remain “open” are the anakinra cohort and 

patients who have a diagnosis other than RA, PsA or AS 

starting any anti-TNF therapy. 

Figure 1: Rituximab recruitment prediction 

(cohort requirement: n = 1100) 

BSRBR data showed that a second anti-TNF is effective in patients who have had 

an unsatisfactory response to the first anti-TNF, and given some insights into 

which sub-populations of patients may gain the best benefits from a second 

anti-TNF. This evidence will be used in ongoing negotiations over access to 

sequential anti-TNF therapy. 

The NICE approach to health economic modelling is to map the change in HAQ 

onto a quality of life score, and then calculate cost effectiveness from this. 

BSRBR analyses have shown that this approach may underestimate 

improvements in quality of life when they are measured directly in RA patients, 

and this observation supports the need to improve current NICE modelling. 

One of the greatest concerns over current access to anti-TNF expressed by 

patients and professionals is the hurdle of a DAS28 of >5.1 in order to have 

access to anti-TNF. There are many clinical situations in which this is 

inappropriately high, such as in patients who need oral steroids to maintain 

disease control. An analysis of BSRBR data, performed with the considerable 

assistance of Kimme Hyrich, Mark Lunt, and Deborah Symmons, showed that 

patients with a baseline DAS of less than 5.1 did just as well as those with a 

DAS28 of >5.1, suggesting that it would be just as cost-effective to use the 

drugs in patients with less active disease than is currently the case. 

I am pleased to be given the opportunity to show colleagues that as well as the 

obvious triumphs of the BSRBR, there is other activity that helps to support 

ongoing negotiations with NICE. I have always found my colleagues in 

Manchester to be extremely helpful in assisting our efforts to ensure that the 

most appropriate RA patients will get access to biological therapies. I am 

confident that they would be equally helpful with other colleagues who may 

have ideas for analyses of BSRBR data. 

Dr Chris Deighton 

BSRBR Steering 

Committee vacancies 2009 

The BSRBR Steering Committee oversees the 

operation of the Register and is directly responsible 

to the BSR Executive. It meets four times a year, 

normally in London. The Committee has 

responsibility in particular for: 

• safeguarding patient safety 

• ensuring financial and contractual obligations 

are met; and 

• ensuring research objectives are being met. 

There is a vacancy for a consultant representative 

on the committee for a three-year term from 

November 2009. The representative would be 

expected to have a particular interest in the scientific 

output (analyses and publications) of the register. 

Applications for membership (on a nomination form) 

are considered by current members of the Steering 

Committee which makes nominations to the BSR 

Executive for appointment. 

To find out more or request a nomination form, 

please contact BSRBR Co-ordinator Nia Taylor 

(DL: 020 8742 0905, ntaylor@rheumatology.org.uk). 

2


www.rheumatology.org.uk 

Conference report 

BSRBR at Rheumatology ‘09 

The BSRBR was well-represented at BSR’s conference at Glasgow’s SECC in April 

this year. The conference attracted around 2,200 attendees over four days and 

feedback from the online evaluation survey was very positive; 95% said they would 

recommend the conference to a colleague, 81% said that the conference is a key 

date in their professional calendar and 91% said that they learnt new things at 

the conference. 

There was a BSRBR stand which was manned by staff from the University of 

Manchester Register team, Pauline Whitelaw and Nia Taylor. 

Seven abstracts from the BSRBR were presented: one oral presentation and six posters. 

The usual lunchtime open BSRBR session was held on the Wednesday of the 

conference. This session attracted a record 300 delegates, so that the packed 

lunches ran out and more had to be ordered! 

Principal Investigators, Professor Deborah Symmons and Dr Kimme Hyrich, gave an 

update on the BSRBR, including rituximab recruitment, adverse event data and 

extended follow-up; Dr Andrew Keat presented the plans for developing a new register 

for ankylosing spondylitis; Debbie Smith gave a round up of the latest news on the 

NICE appraisal of TNF alpha drug switching and Professors David Isenberg and 

Barry Bresnihan talked about the way forward for the BSRBR, including collaboration 

with other European Registries and electronic data capture. 

BSR’s events team have recognized the popularity of the BSRBR’s lunch time meeting 

and, concerned that attendance might be restricted in 2010, when conference will only 

run over three days, they have included the BSRBR session in the main programme. 

This means that it will benefit from advertising in the main programme from 

September and the session will last for an hour and a half instead of 60 minutes. 

So put the dates in your diary: the conference will be held at the 

ICC Birmingham between 21–23 April 2010 and the BSRBR session will be on 

Thursday 23 April 2010 from 13.30 to 15.00 hours. 

UK CRN 

We are delighted to inform you that BSRBR has 

finally been accepted on the portfolio. Our UK 

CRN ID number is 7302. Over the next few months 

we will be uploading all the accrual data for 

2008/2009, which will be co-ordinated centrally 

from the BSRBR office. In addition, we will provide 

figures of registrations prior to 2008 to the 

portfolio. If you have any immediate questions 

regarding this, please do not hesitate to contact 

the office – biologics.register@manchester.ac.uk. 

We will be in contact with you soon regarding your 

accrual data to date. 

➜ 

Change of contact 

Pauline Whitelaw is currently taking six months 

unpaid leave from her post as Policy and 

Projects Administrator, returning early February. 

In her absence please contact Katie Fitzgerald 

at kfitzgerald@rheumatology.org.uk 

BSR members’ survey results 

The most recent membership survey carried out by BSR in May 2009 

asked members for their views on BSR’s new aims and strategic plan. 

Two questions about the Society’s activities were included. As contributors 

to the BSRBR, you will no doubt be pleased to know that the Register 

scored very highly in both questions. 

• 46% rated the Register as ‘very important’ – the highest proportion 

for any activity. 

• The average rating of the Register was third highest of the 16 

activities listed, behind Clinical Guidelines and Annual Scientific 

Conference 

• 51% of responders rated BSR’s performance in relation to the 

Register as ‘very good’ (5 on scale of 1 to 5) 

• The only activity which scored a higher percentage of ‘very good’ 

was Clinical Guidelines 

• The average rating of the Register was the highest of the 16 

activities listed, above that of the Annual Scientific conference, 

Rheumatology Journal and Clinical Guidelines (the next three 

highest ratings) 

3

ABSTRACTS|presented at the BSR AGM 2009 

FACTORS ASSOCIATED WITH WORK DISABILITY IN RHEUMATOID ARTHRITIS 

PATIENTS: RESULTS FROM THE BSR BIOLOGICS REGISTER (BSRBR) 

SMM Verstappen, KD Watson, K McGrother, DPM Symmons, KL Hyrich, on behalf of 

the BSR Biologics Register, arc Epidemiology Unit, The University of Manchester, 

Manchester, United Kingdom. 

Background: Work disability is one of the major economic problems in patients with 

rheumatoid arthritis (RA). Treatment with anti-TNF agents has proven to be clinically 

effective in these patients, but there is limited data available on the effect of biological 

agents on working status in the UK. 

Aim: Using data from BSRBR, (i) to describe working status at start of anti-TNF 

treatment, and (ii) to identify predictors of onset of new work disability. 

Methods: 2,703 consecutive patients with RA registered with the BSRBR between 

01/10/2001 and 01/09/2008 (aged3.2 to 5.1) disease activity. 

Methods: Patients for this study were selected from the BSR Biologics Register if they 

had failed treatment with at least 2 standard DMARDs and fell into the moderate or 

high DAS28 categories. Change in HAQ over the first 12 months of enrolment were 

compared first between anti-TNF treated and untreated patients in each DAS group, 

and then between treated patients in the moderate and high DAS groups. Mean 

change in HAQ was modelled for each comparison using Doubly Robust estimation, 

which fits both a propensity and a linear regression model to minimise bias in the 

estimate. Results were adjusted for age, gender, disease duration, baseline HAQ and 

DAS28 score, number of previous DMARDS and steroid use. 

Results: The analysis included 4772 and 224 anti-TNF treated and 369 and 325 

DMARD only treated patients with high and moderate DAS28 respectively, despite 2 

DMARDs. In both DAS28 groups, anti-TNF treated patients tended towards lower age 

and higher mean DAS28 and HAQ scores at baseline, but had similar disease 

duration. They had also failed on average one more DMARD than the untreated group 

(4 versus 3, p5.1. 

The current UK eligibility criteria for anti-TNF therapy, which limits therapy to patients 

with DAS28>5.1 should be reconsidered, as substantial functional (and therefore 

cost-effective) benefits may also be gained by treating those with moderately active 

disease. 

Baseline DAS28 > 3.2 – 5.1 > 5.1 

Treatment Group DMARD Anti-TNF DMARD Anti-TNF 

(325) (224) (369) (4772) 

HAQ baseline (mean (SD)) 1.43 1.78 1.87 2.06 

(0.75) (0.61) (0.62) (0.55) 

HAQ 12 months (mean (SD)) 1.45 1.51 1.86 1.71 

(0.78) (0.75) (0.63 (0.71) 

Mean change in HAQ (95% CI) 0.02 -0.27 -0.01 -0.35 

(-0.07, 0.1) (-0.4, -0.15) (-0.09, 0.07) (-0.38, -0.32) 

Adjusted Mean Change in HAQ ref -0.24 ref -0.28 

(95% CI) (-0.33, -0.14) (-0.34, -0.23) 

Adjusted Mean Change in HAQ ref -0.05 

(95% CI) (-0.16, 0.06) 

SECULAR CHANGES IN UK ANTI-TNF PRESCRIBING PATTERNS AND TREATMENT 

RESPONSE IN PATIENTS WITH RHEUMATOID ARTHRITIS: RESULTS FROM THE 

BSRBR 

Kath Watson 1 , Kimme Hyrich 1 , Mark Lunt 1 , Deborah Symmons 1 , on behalf of the 

BSRBR 1 

1 

. arc Epidemiology Unit, The University of Manchester, Manchester, United Kingdom. 

Anti-TNF therapy for rheumatoid arthritis (RA) has significantly improved outcomes 

for patients with severe disease. In the UK, changes in financial restrictions and 

increasing experience with their use may have resulted in changes to the way 

clinicians use anti-TNF therapies. The aim of this analysis was to study the trends in 

prescribing patterns of anti-TNF therapies by UK rheumatologists over a 7 year period 

and compare this with changes in response to treatment. Between October 2001 and 

June 2007, 10789 patients with RA were registered with the BSRBR. Baseline 

characteristics were analysed according to year of anti-TNF prescription. Only the first 

course of anti-TNF was included. Treatment response was determined at 6 months 

according to EULAR criteria. Changes in baseline disease characteristics and response 

rates over a seven year period were analysed using univariate linear and logistic 

regression analysis methods. Over these 7 years, the median level of disease activity 

and severity of newly treated anti-TNF patients has significantly decreased (p


(see Table). The median disease duration remained high (9 years in 2007) although 

the proportion of patient with disease 5.1 following failure of ≥2 

DMARDs including methotrexate) (n=766) followed for 6 months. Patients completed 

the EQ-5D, SF-36 and HAQ at baseline and at a 6-month follow-up assessment. 

Predicted EQ-5D scores were estimated using the HAQ (1) or the SF-36 (2) . The mean 

difference between predicted and observed EQ-5D scores at baseline and change 

during the study was tested using the t-test. 

Results: The patients recruited to this study had a mean age of 58, disease duration 

of 12 years and predominance of females (Table). HAQ and SF-36 physical 

component summary score (PCS) indicated considerable physical disability, and the 

patients had low HRQoL scores. Predicted EQ-5D scores were higher than observed 

scores at baseline, although this was only significant where estimated using the HAQ 

(p=0.007). Over 6 months of follow-up patients improved in physical function and 

HRQoL, with change exceeding the minimum important difference (MID) for the HAQ 

(MID 0.20), EQ-5D (MID 0.05-0.07), PCS (MID 2-3) and mental component 

summary scores (MCS) (MID 3). Change in predicted EQ-5D scores (both methods) 

also exceeded the MID, and corresponded well with observed EQ-5D scores. Although 

change in EQ-5D appeared to be underestimated when predicted from HAQ scores 

and overestimated when predicted from the SF-36, neither were significantly different. 

Age Mean (SD) 58.3 (12.2) 

Gender N (%) 583 (76%) 

Disease duration Mean (SD) 11.8 (10.9) 

Baseline 

6-month change 

n=766 n=699 

HAQ Mean (SD) 1.72 (0.71) -0.22 (0.54) 

SF-36 PCS Mean (SD) 20.4 (10.8) 4.6 (10.3) 

SF-36 MCS Mean (SD) 45.0 (11.3) 3.0 (11.4) 

EQ-5D Observed 0.40 (0.33) 0.08 (0.32) 

Predicted (using HAQ) 0.44 (0.26) 0.07 (0.24) 

Difference, mean (95% CI) 0.04 (0.01, 0.07) -0.02 (-0.05, 0.01) 

Observed 0.40 (0.33) 0.08 (0.32) 

Predicted (using SF-36) 0.42 (0.25) 0.10 (0.23) 

Difference, mean (95% CI) 0.02 (-0.01, 0.05) 0.02 (-0.01, 0.05) 

Conclusions: Predicted EQ-5D scores from the HAQ and the SF-36 were reasonable 

estimates of mean baseline and change EQ-5D scores in the RA patients with severe 

disease. However small differences in response to change could have implications in 

assessing the cost-effectiveness of treatments; underestimation of change (e.g. 

EQ-5D estimated from the HAQ) may lead to underestimation of cost-effectiveness, 

whilst over-estimation (e.g. SF-36 to EQ-5D) may overestimate cost-effectiveness. 

For this reason, estimating EQ-5D scores may be valid where no alternative exists or 

for sensitivity analyses, however we recommend that prospective studies should 

include at least one measure of HRQoL which allows the estimation of utilities. 

References (1) Bansback N, Marra C, et al. Arthritis Rheum 2007; 57:963-71. (2) 

Ara R & Brazier J. Value in Health 2008; 1131-43 

THE INFLUENCE OF ANTI-TNF THERAPY UPON CANCER INCIDENCE IN PATIENTS 

WITH RHEUMATOID ARTHRITIS (RA) WHO HAVE HAD PRIOR MALIGNANCY: 

RESULTS FROM THE BSRBR 

WG Dixon, KD Watson, M Lunt, BSRBR Control Centre Consortium, KL Hyrich, DPM 

Symmons, on behalf of the BSR Biologics Register. 

Purpose: Anti-TNF therapy is rarely prescribed to patients with a history of prior 

malignancy following theoretical safety concerns, clinical trial exclusion criteria and 

national guidelines. Thus, there is currently no published evidence regarding the safety 

of anti-TNF therapy in patients with prior malignancy. Our aim was to explore the 

influence of anti-TNF therapy upon the incidence of cancer in patients with prior 

malignancy, using data from a large national register. 

Methods: 10735 consecutive anti-TNF treated patients with RA registered with the 

BSRBR were followed prospectively. They were compared to 3236 patients with active 

RA on disease modifying anti-rheumatic drugs (DMARD). Patients with a malignancy 

prior to registration were identified by record linkage with the UK Office for National 

Statistics (ONS). Further analysis was restricted to these patients. Incident 

malignancies up to 30/9/07 were identified from consultant and patient 

questionnaires and ONS. Local recurrence and metastases were included as incident 

cancers. Carcinoma-in-situ and non-melanoma skin cancers were excluded from both 

prior and incident malignancies. Patients contributed follow-up time until 30/9/07 or 

death, whichever came first. An individual patient could contribute >1 incident 

malignancy. Incidence rate ratios (IRR) were calculated comparing the anti-TNF to 

the DMARD-treated cohorts. Results: 177 (1.6%) anti-TNF and 118 (3.6%) 

DMARD-treated patients had a history of prior malignancy. Registration occurred within 

10 years of the prior malignancy in 75 (42%) of the anti-TNF and 71 (60%) of the 

DMARD treated patients. After median follow-up times of 3.06 and 1.93 years in the 

anti-TNF and DMARD-treated cohorts, there were 13 incident cancers in 11/177 (6%) 

anti-TNF treated patients compared to 10 cancers in 10/118 (8%) DMARD-treated 

patients. The crude rate of incident cancers was lower in the anti-TNF cohort (25.3 

events / 1000 person years (pyrs) (95% CI 13.4, 43.2)) compared to the DMARD 

cohort (41.9 / 1000 pyrs (20.1, 77.1)). The age- and sex-adjusted IRR for anti-TNF vs 

DMARD-treated patients with prior malignancy was 0.53 (0.22-1.26). 17 patients in 

the anti-TNF cohort had prior melanomas compared to 10 in the DMARD cohort. Of 

concern, 3/11 anti-TNF patients with prior then incident malignancy had prior 

melanomas. The time from melanoma to starting anti-TNF therapy was 33%) of patients with ankylosing spondylitis (AS) need to give up work 

before normal retirement. The beneficial clinical effects of anti-TNF therapy seen in 

patients with AS hopefully will lead to less work disability in the future. 

Aim: To describe working status at start of anti-TNF treatment and at three years after 

starting anti-TNF therapy. 

Methods. 229 consecutive patients with AS (aged


Presentation of latest 

results: ACR, Philadelphia, 

October 2009 

We have had two new analyses accepted for oral 

presentation at the ACR in Philadelphia this year 

and one poster: 

Wednesday 21st October 11 – 12:30pm 

Session: RA Clinical Aspects Treatment Outcomes 

Presentation 1: The influence of anti-TNF therapy 

upon incidence of non-melanoma skin cancer 

(NMSC) in patients with rheumatoid arthritis (RA): 

Results from the BSR Biologics Register (BSRBR) 

Presentation 2: Risk of septic arthritis in patients 

with rheumatoid arthritis treated with anti-TNF 

therapy: results from the BSR Biologics Register 

(BSRBR) 

Tuesday 20th October 

Poster: Serious infections in patients with 

Rheumatoid Arthritis (RA) treated with anakinra 

(ANA): Experience from the BSR Biologics Register 

(BSRBR) 

Web-based 

data collection 

We are starting to plan for a web-based data 

collection system for those of you who would 

prefer to enter data directly onto a website 

(for submission to the Register database) 

rather than completing and sending 

paper-based questionnaires. 

Our aim is to create the web entry forms in 

such a way that: 

• it is quicker for you to complete them than 

filling in paper forms (use of drop-down 

lists etc) 

• data is checked as entered, thus reducing 

need to correct errors by the team at 

Manchester. 

We will soon be sending a short survey to those 

of you responsible for sending data, to find out 

how easy you would find it to switch to 

electronic data entry. We also hope to identify 

some sites willing to be the “guinea pigs” for 

this new system. 

If you are interested in discussing this, please 

contact Kath Watson at 

kath.watson@manchester.ac.uk or Nia Taylor at 

ntaylor@rheumatology.org.uk. 

Recent Publications 

For a full list of BSRBR publications list please visit the 

“Health Professionals” area of our website 

(www.manchester.ac.uk/medicine/arc/BSRBR) 

and click on “Publications”. 

Saad AA, Ashcroft DM, Watson KD, Hyrich KL, Noyce PR, Symmons DP; 

British Society for Rheumatology Biologics Register. Persistence with 

anti-tumour necrosis factor therapies in patients with psoriatic arthritis: 

observational study from the British Society for Rheumatology Biologics 

Register. Arthritis Res Ther. 2009; 11(2):R52. Epub 2009 Apr 8. 

Harrison MJ, Dixon WG, Watson KD, King Y, Groves R, BSRBR Control 

Centre Consortium, Hyrich KL, Symmons DP on behalf of the BSRBR. 

Rates of new-onset psoriasis in patients with rheumatoid arthritis receiving 

anti-tumour necrosis factor alpha therapy: results from the BSRBR. 

Ann Rheum Dis. 2009 Feb; 68(2):209-15. 

Lunt M, Solomon D, Rothman K, Glynn R, Hyrich K, The BSRBR Control 

Centre Consortium, BSRBR, Symmons DP, Stürmer T. Different Methods of 

Balancing Covariates Leading to Different Effect Estimates in the Presence 

of Effect Modification. Am J Epidem. 2009 Jan 19. [Epub ahead of print] 

Hyrich KL, Lunt. M, Dixon WG, Watson KD, Symmons. DPM, BSRBR. 

Effects of switching between anti-TNF therapies on HAQ response in 

patients who do not respond to their first anti-TNF drug. Results from the 

national British Society for Rheumatology Biologics Register (BSRBR). 

Rheumatology (Oxford). 2008 Jul; 47(7):1000-5. 

Hyrich KL, Watson KD, Isenberg DA, Symmons DP. The British Society 

for Rheumatology Biologics Register: 6 years on. Rheumatology (Oxford). 

2008 Oct; 47(10):1441-3. 

All BSRBR follow-up extended to 2013 

As already mentioned, we have 

extended the follow-up of all patients 

in the BSRBR to 2013. This means 

that annual follow-ups will be sent out 

after five years of follow-up asking 

about any changes in therapy and any 

serious adverse events that have 

occurred in the past year. Therefore 

we are only interested in those events 

that fulfil our definition of serious and 

those non serious adverse events that 

led to discontinuation of a drug 

(see table). 

Website suggestions? 

Please send suggestions for improvements/information you would 

like to be able to access on the BSRBR website to 

pat.creighton@manchester.ac.uk. 

Definition of serious adverse events 

1. Death 

2. Hospitalisation 

3. IV antibiotics 

4. Significant loss of function 

5. Congenital malformation 

6. Life threatening 

Please also record all events that 

led to a drug discontinuation. 

6



Events of Special 

Interest forms reminder 

We urge you to download our new “Events of Special 

Interest” forms from our website 

www.manchester.ac.uk/medicine/arc/BSRBR under 

the “Health Professionals” section. This is so you 

can complete these forms at the same time as you 

initially report one of these events to us on the 

follow-up form. This means that we will not have to 

bother you for more information on the event at a 

later date and will save you having to access the 

case notes again. The following events are those 

for which we need to have one of these forms 

completed: 

• Aplastic anaemia 

• Central demyelination 

• Congestive heart failure 

• Infusion/immunologic reactions (rituximab only) 

• Lymphoproliferative tumour 

• Myocardial infarction 

• Pregnancy 

• Pulmonary embolism 

• Serious infections 

• Stroke 

• Surgery 

• Tuberculosis 

If not received with the follow-up form, we will 

post the form out to you to enable us to collect 

this information. 

BSRBR Events of Special Interest Forms 

NICE update 

Multiple Technology Appraisals 

Rheumatoid arthritis – drugs for treatment after failure of a TNF inhibitor 

BSR submitted evidence on 10 August 2009 based on the final scope of 

this appraisal. The submission consisted of two papers: one from the arc 

epidemiology unit at Manchester with the latest evidence from the Biologics 

Register and one from the BSR Clinical Affairs Committee based on the 

revised BSR Biologics Guidelines. The appraisal was re-started in November 

2008, following the NICE Appeal Committee’s recommendation that NICE 

reconsider the issue of allowing patients prescription of an alternative 

anti-TNF if their first anti-TNF does not work satisfactorily. The first appraisal 

committee meeting will take place on 4 February 2010. 

Psoriatic arthritis - etanercept, infliximab and adalimumab (review) 

BSR submitted comments on the final scope on 26 August 2009. 

Single Technology Appraisals 

Abatacept - Juvenile idiopathic arthritis 

NICE informed us that this technology appraisal had been suspended, as 

the manufacturer of Abatacept was not in a position to submit evidence 

due to a delay in the regulatory process. We will keep you updated on any 

developments. 

Certolizumab 

BSR submitted an organisational statement for this appraisal in June 2009. 

The first appraisal committee meeting took place on 23 September 2009, 

with the guidance expected to be issued in February 2010. 

Golimumab 

The three appraisals on Golimumab (for the treatment of rheumatoid arthritis 

after failure of previous antirheumatic drugs, for the treatment of rheumatoid 

arthritis (methotrexate-naïve) and for the treatment of ankylosing spondylitis) 

have all been suspended at the request of the manufacturer, as they were 

not in a position to submit evidence. We will keep you updated on any 

developments. 

Tocilizumab 

NICE Appraisal Committee’s preliminary recommendation (1st October) 

is that Tocilizumab is not recommended for the treatment of moderate to 

severe active rheumatoid arthritis. These recommendations are under 

consultation and the deadline for comments is 22nd October 2009. 

Clinical guideline updates 

Tuberculosis - update of clinical guidelines 

BSR is participating in the revision of these guidelines, and took part in the 

stakeholder workshop held on 29 September 2009. 

7


Outstanding Death Data 

update: 50% of requests 

now returned 

We have now had over 1,200 deaths in the 

anti-TNF cohort reported to the BSRBR and, in the 

last newsletter, we outlined a particular problem we 

were having due to missing death information in 

around a third of these patient deaths. One of the 

primary outcomes of the Biologics Register has 

been to study the long-term safety of anti-TNF 

therapy and one of the most important outcomes 

has been death. All patients registered with the 

BSRBR are flagged with the NHS Information 

Centre (formerly the Office for National Statistics). 

Therefore, we are notified of all deaths and receive 

a copy of the death certificate. Unfortunately, we 

do not receive information on whether the patient 

was receiving a biologic drug at the time of death. 

Without these details, it may be necessary to 

exclude these important patients from analyses, 

thus losing all of their information collected to date. 

So far we have received 212 responses from 410 

requests for such death information so we are still 

have 50% outstanding. We realise how difficult it 

can be to obtain this information when a patient 

has died. If you have received one of these letters 

and are having trouble accessing data for any 

reason please contact the office on 

biologics.register@manchester.ac.uk. 

➜ 

Reminder: 

Continued importance of follow-up data! 

If important drug therapy data or details relating 

to a serious adverse event are missing, it will often 

result in data being excluded from forthcoming 

BSRBR analyses, limiting the usefulness of the data 

collected at baseline. At the same time, we do really 

appreciate the burden we are putting on you and your 

team. Again, if you would like a list of patients who are 

not responding to our questionnaires please contact 

Pat Creighton at pat.creighton@manchester.ac.uk. 

Reporting adverse events 

Abbott – Adalimumab 

Chiara Dell'aria Burani BSc, MSc 

Affiliate Safety Representative 

Pharmacovigilance UK, Ireland & Malta 

Abbott UK, Abbott House, 

Vanwall Business Park, 

Vanwall Road, Maidenhead, 

Berkshire SL6 4XE - UK 

PcV: +44 (0)800 121 8267 

Tel +44 (0)1628 644175 

Fax +44 (0)1628 644236 

Email: 

chiara.dellaria-burani@abbott.com 

Biovitrum – Anakinra 

Gema Retama 

Senior Pharmacovigilance Specialist 

Biovitrum 

Quintiles Drug Safety and Medical 

Affairs, Europe Quintiles Ireland 

Limited East Point 

Business Park Fairview 

Dublin 3 

Tel: 0035318195242 

Fax: 0035318099501 

Email: gema.retama@quintiles.com 

Roche – Rituximab 

Dr Boshishi Mohlala, 

Drug Surveillance Physician 

Drug Safety and Risk Management 


It is essential that information on all occurrences of all adverse events on 

registered patients is reported promptly to the BSRBR offices at the arc EU in 

Manchester. All available data for each adverse event should always be provided 

to assist the Register’s pharmacovigilance effort and ensure we have the best 

information to assess the safety of these treatments both short-term and over 

the life of the register. 

If you also notify the MHRA of a suspected adverse drug reaction or a 

suspected defect in a product through the yellow card scheme please will 

you record this in the information provided to the BSBR. 

In addition you may also notify or seek advice from the relevant company in 

relation to safety for each product using the following contacts: 

Roche Products Limited 

6 Falcon Way, Shire Park 

Welwyn Garden City AL7 1TW - UK 

Tel: +44( 0)1707-367554 

Fax:+44 (0)1707 384504 

Email: boshishi.mohlala@roche.com 

Schering Plough – Infliximab 

Graham Marshall 

Drug Safety Manager (UK and Ireland) 

Schering-Plough Ltd 

Welwyn Garden City 

Hertfordshire AL7 1TW - UK 

Tel: +44 (0)1707 363686 

Fax: +44 (0)1707 363696 

Mob: +44 (0)777 197 3280 

Email: graham.marshall@sp.com 

Wyeth – Etanercept 

Catherine Binns RN 

Head of Drug Safety 

Wyeth Pharmaceuticals 

Huntercombe Lane South 

Taplow, Maidenhead 

Berkshire SL6 0PH - UK 

Tel: +44 (0)1628 604377 

Fax: +44 (0)1628414025 

Dir: +44 (0)1628 413931 

Mob: +44 (0)7990 530138 

Email: binnsc@wyeth.com 

For all queries about this newsletter and suggestions for future issues, please contact: 

Nia Taylor, BSR Biologics Register Coordinator 

E: ntaylor@rheumatology.org.uk 

W: www.rheumatology.org.uk 

British Society for Rheumatology, Bride House, 18-20 Bride Lane, London EC4Y 8EE 

Registered Charity No. 1067124 Company No. 3470316, VAT No. 404 5637 66

BSRBR|Newsletter - The British Society for Rheumatology

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