Adalimumab-associated optic neuritis

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Abstract

We present, to our knowledge, the first published cases of optic neuritis associated with adalimumab, a medication in the class of anti-tumor necrosis factor-alpha (TNF-α) antagonists.

Approved in recent years by the FDA, adalimumab (Humira, Abbott Laboratories; Abbott Park, IL) is a recombinant monoclonal antibody that targets and blocks the physiologic effects of TNF. Other TNF antagonists have had associations with optic neuritis and demyelinating events.

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.

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