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and mean erythrocyte sedimentation was 41.2 mm/h. The severe
RA cohort was comparable to patients using etanercept (n = 714),
except that 36% of patients in the severe RA cohort had used two
or more DMARDs prior to cohort entry, whereas 74% of
etanercept patients had used two or more DMARDs.
Compared to the general population, patients with RA who
received DMARD therapy after methotrexate were 4.7-times as
likely to develop non-Hodgkin’s lymphoma and 3.8-times as likely
to develop any lymphoproliferative cancer (table 1). These findings
can be compared with a recent population-based, prospective
cohort study from the UK,7 which followed 2105 patients with
new onset inflammatory polyarthritis for an average 7.4 years. By
the fifth year, 59% of patients satisfied the 1987 American College
of Rheumatology (ACR) criteria for RA. Among patients who ever
used methotrexate, the SIR for any lymphoma was 4.86 (95% CI,
1.78–10.57). Although our study was not planned to estimate risk
among the etanercept patients, we wish to report that follow-up
in the etanercept cohort was 1428 person-years, with none of these
patients developing a lymphoproliferative cancer.
The key strengths of this study are the community-based
setting and the availability of comprehensive data. While we did
not verify the diagnoses of RA directly, our definition of severe
RA has strong face validity. We believe results from this study
may be useful to interpret the frequency of lymphoproliferative
cancers among patients with severe RA who have received anti-
TNF therapies.
L J Herrinton,1 L Liu,1 S Shoor,2 D Mines3
1
Division of Research, Kaiser Permanente Northern California, Oakland, California,
USA; 2 Department of Rheumatology, Kaiser Medical Center, Santa Clara, California,
Guillain–Barré syndrome in a patient
receiving anti-tumour necrosis
factor a for rheumatoid arthritis: a
case report and discussion of
literature
Tumour necrosis factor a (TNFa) is a proinflammatory cytokine
that is involved in the pathogenesis of rheumatoid arthritis
(RA).1 Anti-TNFa has been shown to have a significant effect in
delaying the joint destruction associated with this condition,
and is being used with increasing frequency. The side effects are
well documented, but further information continues to emerge
and advice regarding how to proceed thereafter remains
limited.2
We report on a 46-year-old woman with a 6-year history of
seropositive erosive RA. Despite combination disease-modifying
antirheumatic drugs (DMARDs) she remained symptomatic
and had a 28-joint Disease Activity Score (DAS28) of 6.27. She
was started on anti-TNFa therapy in 2004 and received three
infliximab infusions, resulting in a fall in the DAS28 score to
4.16.
She was admitted to hospital 5 weeks after the last infusion
having developed paraesthesia and weakness of her hands and
lower limbs. There was a preceding history of cough and malaise
for 10 days. She had reduced power in her lower limbs, reduced
knee and ankle reflexes and mute plantar responses.
Ann Rheum Dis April 2008 Vol 67 No 4
Letters
USA; 3 Global Safety Surveillance and Epidemiology, Wyeth Research, Collegeville,
Pennyslvania, USA
Correspondence to: L J Herrinton, Division of Research, Kaiser Permanente Northern
California, 2000 Broadway, Oakland, CA, 94612, USA; Lisa.Herrinton@kp.org
Funding: This research was supported by a contract from Wyeth Research.
Competing interests: This study was sponsored by Wyeth (Madison, New Jersey,
USA), which produces and markets etanercept (Enbrel). Kaiser Permanente
investigators had control over publication. One author (DM) is employed by Wyeth and
owns company stock.
Accepted 27 July 2007
Ann Rheum Dis 2008;67:574–575. doi:10.1136/ard.2007.075986
REFERENCES
1. Mellemkjaer L, Linet MS, Gridley G, Frisch M, Moller H, Olsen JH. Rheumatoid
arthritis and cancer risk. Eur J Cancer 1996;32A:1753–7.
2. Gridley G, McLaughlin JK, Ekbom A, Klareskog L, Adami HO, Hacker DG, et al.
Incidence of cancer among patients with rheumatoid arthritis. J Natl Cancer Inst
1993;4:85:307–11.
3. Tennis P, Bombardier C, Malcolm E, Downey W. Validity of rheumatoid arthritis
diagnosis listed in the Saskatchewan Hospital Separations Database. J Clin Epidemiol
1993;46:675–83.
4. Baecklund E, Iliadou A, Askling J, Ekbom A, Backlin C, Granath F, et al. Association of
chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid
arthritis. Arthritis Rheum 2006;54:692–701.
5. Wolfe F, Michaud K. Lymphoma in rheumatoid arthritis: the effect of methotrexate
and anti-tumor necrosis factor therapy in 18,572 patients. Arthritis Rheum
2004;50:1740–51.
6. Brown SL, Greene MH, Gershon SK, Edwards ET, Braun MM.
Tumor necrosis factor antagonist therapy and lymphoma development: twenty-six
cases reported to the Food and Drug Administration. Arthritis Rheum
2002;46:3151–8.
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primary care derived cohort of cases of inflammatory polyarthritis. Ann Rheum Dis
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A lumbar puncture revealed a raised cerebrospinal fluid (CSF)
protein level at 0.83 g/dl. Neurophysiology studies demonstrated
an acquired segmental demyelinating polyneuropathy consistent
with Guillain–Barré syndrome (GBS). She was transferred to the
neurology unit where she improved spontaneously.
The development of GBS in our patient may have been
triggered by an upper respiratory tract infection or be secondary
to her anti-TNFa treatment. At present she remains off anti-
TNFa therapy.
GBS is defined as an acute peripheral neuropathy causing limb
weakness that progresses over days or weeks.3 The annual
incidence is 1.5 cases per 100 000 and the mortality rate around
5%. Approximately 10% of patients will be severely disabled at
1 year.4 The possible precipitants include infection, underlying
systemic disease and malignancy.5
The US Food and Drug Administration’s Adverse Events
Reporting System suggests that nine cases of GBS have arisen in
patients taking infliximab. Of these, four had RA and all were
female. One patient had a recurrence of GBS when re-challenged
with etanercept. There are also reports of GBS occurring in five
patients receiving etanercept and one taking adalimumab.8 This
indicates this is a rare complication.
We found two published case reports of patients with GBS
associated with anti-TNFa. In one a patient with psoriatic
arthropathy and a previous history of GBS had a recurrence of
neurological symptoms on receiving infliximab.6 Another
describes GBS and Miller–Fisher syndrome occurring in a
patient given infliximab for RA.9
The British Society of Rheumatology (BSR) guidelines for
prescribing TNFa blockers recommend avoidance of these
575
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Letters
agents in patients with pre-existing demyelinating disease. In
patients without previous problems they suggest withdrawal of
therapy if demyelination occurs, but do not make a comment
on whether it is appropriate to try an alternative anti-TNFa
agent.7
Guidelines regarding how to proceed with treatment after an
adverse reaction to one TNFa blocker would be welcome.
S Silburn, E McIvor, A McEntegart, H Wilson
Department of Rheumatology, Stobhill Hospital, Glasgow, UK
Correspondence to: S Silburn, Rheumatology Department, Ninewells Hospital,
Dundee, DD1 9SY, UK; suzysilburn@hotmail.com
Competing interests: None declared.
Accepted 7 June 2007
Ann Rheum Dis 2008;67:575–576. doi:10.1136/ard.2005.043208
576
REFERENCES
1. Khanna D, McMahon M, Furst DE. Safety of tumour necrosis factor-alpha
antagonists. Drug Safety 2004;27:307–24.
2. Mikuls TR, Weaver AL. Lessons learned in the use of tumour necrosis factor-alpha
inhibitors in the treatment of rheumatoid arthritis. Curr Rheumatol Rep 2003;5:270–7.
3. Kuwabara S. Guillain-Barre syndrome: epidemiology, pathophysiology and
management. Drugs 2004;64:597–610.
4. Raphael JC. Present treatment of Guillain-Barre syndrome. Bull Acad Natl Med
2004;188:87–94.
5. Avila-Funes JA, Mariona-Montera VA, Melano-Carranza E. Guillain-Barre syndrome:
etiology and pathogenesis. Rev Invest Clin 2002;54:357–63.
6. Cisternas M, Gutierrez M, Jacobelli S. Successful rechallenge with anti-tumor
necrosis factor a for psoriatic arthritis after development of demyelinating nervous
system disease during initial treatment: comment on the article by Mohan et al.
Arthritis Rheum 2001;44:2862–9.
7. British Society for Rheumatology. Update of BSR guidelines for prescribing TNF
blockers in adults with rheumatoid arthritis. London, UK: BSR, 2004.
8. Information for the Arthritis Advisory Committee. http://www.fda.gov/search/
databases (accessed 28 January 2008).
9. Shin IS, Baer AN, Kwon HJ, Papadopoulos EJ, Siegel JN. Guillain–Barré and Miller–
Fisher syndromes occurring with tumor necrosis factor alpha antagonist therapy.
Arthritis Rheum 2006;54:1429–34.
Ann Rheum Dis April 2008 Vol 67 No 4
 Downloaded from http://ard.bmj.com/ on March 18, 2015 - Published by group.bmj.com

Guillain−Barré syndrome in a patient

receiving anti-tumour necrosis factor α for
rheumatoid arthritis: a case report and
discussion of literature
S Silburn, E McIvor, A McEntegart and H Wilson

Ann Rheum Dis 2008 67: 575-576

doi: 10.1136/ard.2005.043208

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