Adalimumab-associated optic neuritis
Introduction
This report describes two cases of adalimumab-associated optic neuritis, the first to be published to our knowledge. Approved in 2003 by the FDA for treatment of rheumatoid arthritis, adalimumab is a recombinant monoclonal antibody with a human Fc fragment and a murine Fab fragment that targets tumor necrosis factor (TNF) in the bloodstream, thus preventing related pathophysiologic effects in diseases such as autoimmune arthritis. Other medications in the same class as adalimumab, e.g., etanercept and infliximab, have clear associations with demyelinating events.
Section snippets
Case report #1
A 55-year-old man with type II diabetes mellitus, psoriatic arthritis, and hyperlipidemia, but with no previous ocular disease presented with 5 days of decreased central vision in his right eye (OD). There was no pain with eye movement and no other visual or somatic complaints. Neither he nor his family members had a history of previous neurologic disease.
The patient's treatment history began with a 3-week course of 15 mg/week oral methotrexate which failed to alleviate a severe psoriatic rash
Discussion
The cell-mediated immune response is highly dependent on TNF-α, a cytokine secreted by T-cells and macrophages. Elevated levels of TNF are an essential feature in the pathophysiology of autoimmune arthritis and likely contribute to inflammatory central nervous system (CNS) demyelination, as demonstrated by both in vitro and in vivo experiments [1].
A relatively new class of therapeutic agents, including FDA-approved infliximab (Remicade, Centocor, Inc; Malvern, PA, USA), etanercept (Enbrel,
Conclusion
Optic neuritis and demyelinating diseases of the CNS appear to be associated with adalimumab therapy as well as with other TNF antagonists. Typical findings are unilateral presentation several months to a year into treatment, optic nerve enhancement on MRI, and partial or complete recovery with or without corticosteroid therapy. The pathogenic mechanisms are unknown.
The class of medications to which adalimumab belongs appears to cause de novo occurrence of demyelinating events or may
Acknowledgements
This work was supported in part by an Unrestricted Grant from Research to Prevent Blindness, Inc. NY, NY; Fund for the New Jersey Blind, Newark, NJ; Lions Eye Research Foundation of New Jersey, Newark, NJ; the Eye Institute of New Jersey, Newark, NJ; and the Gene C. Coppa Memorial Fund.
The authors have no conflicting affiliations or financial interests related to the corporate entities mentioned in this article.
References (13)
- et al.
Association between tumor necrosis factor alpha and disease progression in patients with multiple sclerosis
N Engl J Med
(1991) - et al.
Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2
Neurology
(1996) - et al.
Demyelination occurring during anti-tumor necrosis factor alpha therapy for inflammatory arthritides
Arthritis Rheum
(2001) TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study
Neurology
(1999)- et al.
Retrobulbar optic neuritis associated with infliximab in a patient with Crohn disease
Ann Intern Med
(2004) - et al.
Retrobulbar optic neuritis associated with infliximab
Arch Ophthalmol
(2002)
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