Rheumatoid Arthritis

Rheumatoid Arthritis
June 6, 2011
Deborah S. Collier, MD
Rheumatology Unit
Massachusetts General Hospital
Harvard Medical School

I have
no industry
sponsorship or
affiliations

Focus of today’s review
• Overview
• 7 questions for patient with RA to PCP

Rheumatoid Arthritis: Epidemiology
• Systemic inflammatory arthritis than can also involve
internal organs
• Female: male ratio = 2.5:1
• Prevalence ~ 1%, peak 30 – 55 years old
• Genetic predisposition (HLA-DRB1)
• Environmental risk factors: cigarette smoking, infection
• Shortens life span, causes disability
de Vries N, et al. Arthritis Rheum 2002 Apr;46(4):921-8. Pincus T, et al. J Rheumatol. 1989
Klareskog L , et al. Arthritis Rheum. 2006;54:38-46. Pincus T, et al. J Rheumatol. 1987.

Rheumatoid Arthritis: Clinical Features
• Symmetrical polyarthritis
• Morning stiffness
- Lasting ≥ 1 hour
• Rheumatoid nodules
• Limited range of motion
• Extraarticular involvement:
eye, lung, heart, muscle,
vasculature

RA: Erosive Arthritis

Rheumatoid Arthritis: Treatment
Then…
…and Now

History of DMARD* Use in the United States
Anti-IL6
↓ T-cell activation
Anti-CD20
Tocilizumab
Abatacept
Rituximab
Anti-TNF Etanercept, Infliximab, Adalimumab, Certolizumab, Golimumab
Leflunomide
Methotrexate
Penicillamine
Sulfasalazine
Antimalarials
Aspirin Cortisone
Gold
1900
1940 1950 1960 1970 1980 1990 2000
2010
*DMARD = Disease Modifying Anti-Rheumatic Drug
= biologic

Rheumatoid Arthritis: Treatment
…from first suspicion in
PCP’s office to optimal
treatment by rheumatologist
in 6-12 months…

7 RA questions from patient to PCP…
• risk factors for RA
• adverse effects of DMARDs (disease modifying antirheumatic
drugs)
• safety of immunizations in patients on DMARDs
• Safety of biologics in patients with hepatitis

My mother has RA. Are there
any life style changes that I can
make to avoid getting it myself
A. loose weight
B. quit smoking
C. keep immunizations up to date
D. all of the above

My mother has RA. Are there
any life style changes that I can
make to avoid getting it myself
A. lose weight
B. quit smoking
C. keep immunizations up to date
D. all of the above

Smoking and RA
- RR of developing RA = 1.4 for women who smoke >25 cigarettes a
day, compared to non-smokers
- In HLA-DRB4 (+) patients, RR of developing RA is 5.6 in smokers,
compared to non-smokers
- RA patients with > 25 pack year history are more likely to be seropositive,
have nodules, have bony erosion
- Risk of developing RA returns to baseline 10 years after quitting
smoking
Karlson, Arthritis Rheum 1999. Padyokuv, Arthritis Rheum 2004.
Saag, Ann Rheum Dis 1997. Criswell, Am J Med 2002.

What are the risks of being on a
biologic medication for RA

Toxicities of Biologics
TNF’s, rituximab, adalimumab
• Injection site/infusion reactions
• Serious infections
• Opportunistic infections (TB, fungal)
• Malignancy
Rituximab specific
• Progressive multifocal leukoencephalopathy (PML)
Anti-TNF specific
• Demyelination (MS-like syndrome)
• Drug-induced lupus
• Congestive heart failure
Ellerin, Arthritis Rheum. 2003.
Mohan, Arthritis Rheum 2001.
Kwon, Ann Intern Med 2003.

Serious Infections in Pt’s on Biologics
Bacteria
Streptococccus pneumoniae
Listeria monocytogenes
Mycobacteria
Mycobacterium tuberculosis *
Mycobacterium aviumintracellulare
(MAC)
Fungi
Candida albicans
Pneumocystis jiroveci
Aspergillus fumigatus
Histoplasma capsulatum
Cryptococcus neoformans
Coccidioides immitis
* make sure pt is PPD (-)
Ellerin, Arthritis Rheum. 2003.

I am on etanercept for my RA.
Is it true that this drug can
cause cancer
You tell the patient:
A.Anti-TNF’s are associated with definite risk of solid tumors
B.Anti-TNF’s are associated with definite risk of skin cancer
C.Anti-TNF’s are associated with definite risk of lymphoma
D.Anti-TNF’s are associated with definite risk of leukemia

I am on etanercept for my RA.
Is it true that this drug can
cause cancer
You tell the patient:
A. anti-TNF’s are associated with definite risk of solid tumors
B. anti-TNF’s are associated with definite risk of skin cancer
C. anti-TNF’s are associated with definite risk of lymphoma
D. anti-TNF’s are associated with definite risk of leukemia

Malignancy in RA patients on anti-TNF’s –
Conflicting Data
* RR of lymphoma in RA pt’s compared to general population is 2.0
• melanomatous and non-melanomatous cancer increased in RA pt
on anti-TNF, odds ratio 1.5 and 2.3 respectively 1
• conflicting data on risk of lymphoma in RA pt on anti-TNF 2
• conflicting data on risk of solid tumors in RA pt on anti-TNF 3
1
Wolfe, Arthritis Rheum. 2007. (53,000 pts)
2
Bongartz, JAMA. 2006. (3,500 pt’s – increased lymphoma risk)
2
Askling, Ann Rheum Dis. 2005. (53,000 pts – no increased lymphoma risk)
3
Geborek, Ann Rheum Dis. 2005 (800 pts – increased risk of solid tumors)
3
Bongartz, JAMA. 2006. (3,500 pts – increased risk of solid tumors)
3
Askling, Ann Rheum Dis. 2005 (53,000 pts – no increased risk of solid tumors)
3
Wolfe, Arthritis Rheum. 2007. (53,000 pts – no increased risk of solid tumors)

I am on infliximab for RA and am
travelling to South America. Can I
get the yellow fever vaccine

I am on infliximab for RA and am
travelling to South America. Can I
get the yellow fever vaccine
NO!
No live viral vaccines for patients on biologics:
• yellow fever
• MMR
• zoster, varicella
• oral polio
• small pox

Immunization with biologic therapies in RA
RECOMMENDED:
• Tetanus
• Diphtheria
• Inactivated polio
• Pneumococcal
• Influenza
• Hepatitis B
CONTRAINDICATED:
• Oral polio *
• Yellow fever
• MMR
• Varicella
• Small pox *
• Zoster
* Should not be used in household
contacts, avoid contact for 1 month

I am on methotrexate and
hydroxychloroquine for RA. Are there
any vaccines I cannot get

I am on methotrexate and
hydroxychloroquine for RA. Are there
any vaccines I cannot get
NO!
All vaccines (live, killed, attenuated) are safe in patients on nonchemotherapy
doses of non-biologic DMARDs including:
• methotrexate (< 0.5 mg/kg/wk)
• hydroxychloroquine
• leflunomide
• azathioprine (< 3 mg/kg/day)
Lacaille D, Arthritis Rheum. 2008.

I have been on Remicade
(infliximab) for 5 years, can I
get off of it

I have been on Remicade
(infliximab) for 5 years, can I
get off of it
Maybe… it’s worth a try.

When biologic discontinued after remission achieved:
• Sustained remission in 50-70% of patients, 2-7
years after stopping infliximab
• Best predictors of sustained remission are early
treatment with and response to biologics
• My empiric approach: taper off biologic once
sustained clinical remission achieved by cutting
dose in ½, increasing interval between doses
van den Broek, Ann Rheum Dis. 2011.
Tanaka, Ann Rheum Dis. 2010.
Van der Kooij, Ann Rheum Dis. 2009.

I have viral hepatitis and
seropositive (RF+/CCP+)
rheumatoid arthritis. Is it safe
to start Humira (adalimumab)
A. OK to treat with anti-TNF in hepatitis B
B. OK to treat with anti-TNF in hepatitis C
C. OK to treat with anti-TNF in hepatitis B and C
D. Not OK to treat with anti-TNF in hepatitis B or C

I have viral hepatitis and
seropositive (RF+/CCP+)
rheumatoid arthritis. Is it safe
to start Humira (adalimumab)
A. OK to treat with anti-TNF in hepatitis B
B. OK to treat with anti-TNF in hepatitis C
C. OK to treat with anti-TNF in hepatitis B and C
D. not OK to treat with anti-TNF in hepatitis B or C

Anti-TNF’s are safe in hep C, not hep B
• anti-TNF’s do not increase LFT’s or hep C viral load
• anti-TNF’s can be started before or during anti-viral
therapy for hepatitis C
• anti-TNF’s delay the clearance of hep B
• anti-TNF’s may lead to reactivation of latent hep B
• all HBsAg+ patients should receive antiviral
therapy prior to or together with the initiation of
immunosuppressive therapy
J Hepatol 2009.
Roux CH, Rheumatology. 2006.
Peterson JR, Ann Rheum Dis. 2003.

Take Home Messages
1. Smoking increases risk and severity of RA
2. Anti-TNF’s have definite risk of skin cancer and infection,
possible risk of lymphoma or solid tumors
3. Make sure patient is PPD negative before starting biologic
4. No live viral vaccines for patients on biologics
5. Anti-TNF’s are safe in active hepatitis C, not active hepatitis B