Multicenter Study of Infliximab for Refractory Uveoretinitis in Behçet Disease Okada AA, Goto H, Ohno S, Mochizuki M; Ocular Behçet’s Disease Research Group of Japan. Multicenter study of infliximab for refractory uveoretinitis in Behçet disease. Arch Ophthalmol. 2012;130(5): Copyright restrictions may apply

Introduction Behçet disease affected more than individuals in Japan in 2008 and represented the cause of uveitis in roughly 6% of new patient referrals to specialty clinics. Patients who have Behçet disease with active uveitis have been shown to have increased tumor necrosis factor production by peripheral monocytes compared with patients without active uveitis or control subjects. Infliximab, a chimeric monoclonal antibody against tumor necrosis factor, has been shown to be clinically effective in several autoinflammatory conditions and was officially approved in Japan for the specific indication of refractory uveoretinitis in patients with Behçet disease. The aim of this study was to describe the effects of infliximab on uveitis in patients with Behçet disease during the first year of treatment. Copyright restrictions may apply

Prospective collection of clinical data was mandated by the Japanese Ministry of Health, Labour, and Welfare for this indication. Data were collected from patients who commenced infliximab therapy between January 26, 2007, and August 23, 2008, at 8 participating tertiary centers. All patients had uveoretinitis refractory to immunosuppressive therapy or were judged to be intolerant of such therapy. After medical clearance, infliximab at the approved dose of 5 mg/kg was infused at weeks 0, 2, and 6 and every 8 weeks thereafter. Concomitant therapy was left to physician discretion. Methods

Copyright restrictions may apply Study Limitations: –Of 97 eligible patients, data were obtained for only 63 patients. –Efficacy and severity ratings were not defined. –Only inflammatory attacks observed at clinic visits were counted. Thus, there may have been underreporting of asymptomatic or mild attacks that did not prompt the patient to seek examination. –The infliximab dosing was fixed, and some patients may require larger or more frequent doses. –The effect of concomitant immunosuppressive therapy was not evaluated. –A follow-up of 1 year may be inadequate to fully assess the efficacy and safety of infliximab therapy in Behçet disease. Methods

Copyright restrictions may apply Among the 63 patients, 56 (89%) were male and 44 (70%) were aged 24 to 44 years. A total of 34 episodes of adverse effects occurred in 29 patients (46%), including 3 episodes of infusion reactions. None were serious. Of note, 1-year efficacy was assessed after excluding 15 patients who had previously received infliximab or in whom data were incomplete. At 1 year, the uveoretinitis: –Had improved in 69% (33 of 48 cases). –Had improved somewhat in 23% (11 of 48 cases). –Was unchanged in 8% (4 of 48 cases). –Had worsened in no patients. Results

Copyright restrictions may apply The mean number of ocular attacks per 6-month period decreased from 2.66 at baseline to 0.44 during months 1 through 6 and to 0.79 during months 7 through 12. Among 48 patients, 21 (44%) had no ocular attacks during the 1-year period. The mean best-corrected visual acuity improved from logMAR at baseline to logMAR at the end of 1 year (P =.01). Results

Copyright restrictions may apply Efficacy of Infliximab by Location and Severity of Ocular Inflammatory Attacks a Results

Copyright restrictions may apply The use of infliximab for refractory uveoretinitis in Behçet disease in Japan represents the first regulatory agency–approved use of a biologic agent for any uveitis indication. This multicenter study concluded overwhelmingly good safety and efficacy for this treatment in a large number of patients, although these conclusions must be interpreted with the study limitations in mind. Further evaluation of longer follow-up, the effect of concomitant immunosuppressive agents, and a scheme for severity grading is currently under way. Comment

The utility of biologic agents in various types of uveitis remains unclear. Biologic agents have potentially severe adverse effects and are extremely expensive. From a public policy perspective, the utility of these agents requires careful scrutiny. Copyright restrictions may apply Comment

If you have questions, please contact the corresponding author: –Annabelle A. Okada, MD, Department of Ophthalmology, Kyorin University School of Medicine, Shinkawa , Mitaka, Tokyo , Japan Copyright restrictions may apply Contact Information