Anti-TNF-alpha Therapy for Arthritis Linked to Demyelinating CNS Lesions

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Anti-TNF-alpha Therapy for Arthritis Linked to Demyelinating CNS Lesions

NEW YORK (Reuters Health) Jan 16 - Tumor necrosis factor-alpha (TNF-alpha)

blockade in patients with inflammatory arthritis may be a risk factor for

demyelinating CNS lesions or other forms of white matter injury, US researchers

warn.

Patients receiving anti-TNF-alpha therapy should be monitored for new-onset

neurological signs and symptoms suggestive of demyelination, the team

recommends. If such signs appear, the drug should be discontinued immediately

and the patient should be referred for a thorough neurologic examination, MRI,

and lumbar puncture, and perhaps a brain biopsy if the clinical and/or

radiographic course is rapidly progressive.

The potential problem came to the attention of Dr. Niveditha Mohan, of

town University Medical Center in Washington, DC, and colleagues when a

48-year-old man was referred with fever, confusion, and gait disturbance after

receiving etanercept (Enbrel) for 4 months.

A brain biopsy revealed white matter changes, but no demyelination was visible

on MRI. " The final reading of the biopsy was most consistent with a

leukoencephalopathy, " the researchers report in the December issue of Arthritis

& Rheumatism.

They searched the Adverse Events Reporting System (AERS) of the US Food and Drug

Administration and identified 19 other patients who developed neurologic

symptoms suggestive of demyelination during anti-TNF-alpha therapy (etanercept

in 17 patients and infliximab in 2). Eighteen of those patients and the index

patient underwent MRI, which showed demyelination in one or more areas of the

CNS, or other forms of white matter injury.

The average length of therapy before symptom development was 5 months (range 1

week to 15 months). In all patients, symptoms improved completely or partially

after discontinuation of anti-TNF-alpha therapy, and when one patient was

rechallenged with etanercept his symptoms recurred.

" A literature search for reports of demyelination associated with other

concomitant medications yielded negative results, " Dr. Mohan and her associates

write.

Therefore, they point out, the association between neurological events and

anti-TNF-alpha therapy meets all five primary elements recently proposed as

criteria for identifying environmentally associated rheumatic disorders:

temporal relationship, lack of alternative explanations, dechallenge,

rechallenge, and biological plausibility.

Still, in correspondence with Immunex, the manufacturer of etanercept, the

investigators learned that 77,152 patients were exposed to etanercept from

November 1998 through May 2000, and symptoms suggestive of a demyelinating

disorder were reported for only 9 patients during this period.

Furthermore, the patients " could have had a genetic propensity to develop MS,

which may have been exacerbated by the administration of an anti-TNF-alpha

agent, " the authors point out. There was a prior history of MS or an MS-like

syndrome in four patients.

" Clinicians should consider avoiding anti-TNF-alpha therapy in those patients

who have a preexisting diagnosis of MS, " Dr. Mohan's group recommends, " and

should be cautious with its use in those with a strong family history of MS. "

Arthritis Rheum 2001;44:2862-2869.