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Dr. Levinson, Department of Ophthalmology, Division of JSEI Treatment Centers, Ocular Inflammatory Disease Center, UCLA Comprehensive Ophthalmology Division, Los Angeles, CA.
Dr. Cunningham, The Uveitis Service, department of ophthalmology, California Pacific Medical Center, San Francisco, CA.
Dr. Dunn, associate professor of ophthalmology, division of ocular immunology. The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore.
Dr. Rosenbaum, professor, Medicine and Ophthalmology, Joint Professor, Cell and Developmental Biology, Casey Eye Institute, Oregon Health & Science University, Portland.
Editor's Note: As defined by the FDA, the term "biologics" refers to a wide range of products that includes vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins, such as monoclonal antibodies and antibody fragments.
A number of biologic agents have either been approved or are in clinical trials for the treatment of systemic inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, psoriasis, and Crohn's disease, so it is only natural that many of these agents have been used off label in patients with more severe and sight-threatening uveitis. The best characterized of these agents are the tumor necrosis factor (TNF) inhibitors infliximab (Remicade, Centocor), etanercept (Enbrel, Amgen, Wyeth), and adalimumab (Humira, Abbott). The IL-1 inhibitor anakinra (Kineret, Amgen) and selected T-cell neutralizing agents also have been used, but to a much lesser extent.
Our panel discusses what is now a very limited, but growing, experience with the use of these agents to treat ocular inflammatory disease.
When do you consider using a biologic agent to treat ocular inflammatory disease? Are there any conditions for which biologic agents should almost always be considered?
James P. Dunn, MD: I consider using the biologics much as I would consider using more conventional anti-inflammatory therapy-that is, the decision is based on the condition and its severity, response to previous therapy, side effects from previous therapy, and the patient's medical profile. I tend to be conservative regarding new therapies, so I don't use the biologics unless other treatments with a longer track record have been tried or are specifically contraindicated. It's less a case of when the biologics should be considered than when they shouldn't; TNF antagonists, for example, shouldn't be used in patients with infectious uveitis, malignancies, or demyelinating diseases.
Ralph Levinson, MD: I would consider using a biologic agent in several situations. Most often, I have used them either in individuals who have another diagnosis for which TNF inhibitors are used, such as juvenile rheumatoid arthritis-associated uveitis, or in chronic uveitides that require prolonged immunomodulatory therapy. In the latter, there is the practical issue of expense and getting insurance companies to pay for the agent, so I generally use it when antimetabolites or cyclosporine either cannot be used or are not sufficient. In any case, I have been using infliximab in this situation, and usually use another agent, such as methotrexate or other antimetabolite or cyclosporine, to prevent autoantibody formation. Therefore, it makes sense to try one of those agents first.
I have only once used infliximab for acute disease, a case of severe acute HLA-B27-associated anterior uveitis in a patient who was traveling and needed a rapid response. Infliximab is an expensive and potentially risky alterative, but it has the benefit of having a rapid onset in someone who cannot tolerate corticosteroids and has a condition such as an acute episode of Behcet's disease.
James T. Rosenbaum, MD: The term biologic is very broad, so I would be cautious about extrapolating from one biologic to another, especially if the agents have different mechanisms of action. Currently the most widely used biologic agents for immune-mediated diseases are TNF inhibitors. The data in support of either etanercept or adalimumab are too limited to support the use of either currently for uveitis in a non-study setting. The data in support of infliximab are more extensive, and this agent could be considered for patients in whom oral corticosteroids and at least one other immunosuppressive agent have failed. For patients with uveitis and Behcet's disease, the data for efficacy with infliximab are particularly strong, and this agent should be considered early in disease management.