LETTER TO THE EDITOR - Humira-associated multiple sclerosis

[Guest guest]

Journal of Rheumatology

Letter to the Editor

Jan 2007

Adalimumab-Associated Multiple Sclerosis

To the Editor:

Several cases of demyelinating diseases have already been reported

during the course of tumor necrosis factor-a (TNF-a) antagonists. We

describe a case of multiple sclerosis (MS) where onset was associated

with adalimumab.

A 32-year-old woman with rheumatoid arthritis (RA), who had

unsuccessfully been taking methotrexate for 16 months, started taking

adalimumab in April 2003 (40 mg/2 weeks). In March 2005, she reported

an acute loss of vision with pain in her left eye. A retrobulbar optic

neuritis was diagnosed. Adalimumab was discontinued and a 3-day course

of high-dose methylprednisolone started. Her visual acuteness improved

but an afferent papillary defect remained in her left eye. Magnetic

resonance imaging (MRI) demonstrated multiple lesions in the white

matter with high signal intensities (T2-weighted images) and

enhancement after gadolinium (T1-weighted images) in the right and

left semi-oval centers. Three months later, the MRI showed new

gadolinium enhancing lesions leading to the diagnosis of MS according

to the revised Mc criteria1.

The temporal relationship between adalimumab and MS and the partial

improvement of optic neuritis after its discontinuation raise the

question of the role of adalimumab. So far, only 2 cases of optic

neuritis had been published with adalimumab, one with isolated optic

neuritis and one with numerous central nervous system (CNS) plaques of

various ages and a painful retrobulbar optic neuritis2. Four

additional cases of CNS demyelination have been identified during the

adalimumab clinical development program. One patient presented with

optic neuritis and the other 3 with paresthesia. One of them had a

prior diagnosis of probable MS3.

A link between TNF-a antagonists and a demyelinating disease is

suggested by several studies. Based on the TNF-a overproduction in

serum and cerebrospinal fluid of patients with MS4 and the effect of

TNF-a antagonists in animal models5, a double-blind,

placebo-controlled trial in MS with lenercept (TNF-a antagonist close

to etanercept) was conducted. Unfortunately, this led to a shortening

of time to flare, and a worsening of the neurological condition6.

Similar outcomes have also been observed in an open-label trial with a

monoclonal anti-TNF antibody in 2 patients with rapidly progressive

MS7.

These studies suggest that TNF-a antagonists may potentially initiate

or unmask an underlying demyelinating disease. New onset, flare, or

worsening of demyelinating diseases including MS have been associated

with the 2 other marketed TNF-a antagonists (17 with etanercept and 2

with infliximab)8. An update through August 2002 from the US Food and

Drug Administration's AERS database has also reported several cases of

demyelination associated with infliximab, but detailed information

about these cases is not published3. In the French adverse event

reporting system database, 4 demyelinating disorders (worsening 1, new

onset 3) have been reported during treatment with infliximab over 4

years and etanercept over 5 years, respectively. However, all these

data must be tempered by cases of demyelinating diseases recently

reported in patients with RA who were not receiving any TNF-a

antagonists9.

Like other TNF-a antagonists, adalimumab must be stopped if a

neurological event occurs and should be avoided in patients with

preexisting or suspected demyelinating diseases.

http://www.jrheum.com/subscribers/07/01/239.html

--

Not an MD