Infliximab in Uveitis Treatment

We appreciate Dr Suhler et al¹ for studying infliximab prospectively for the treatment of refractory uveitis and for the scientific manner in which they evaluated the treatment. We did want to make several points regarding their treatment protocol that may have influenced their associated adverse events. These events are unexpected given that multiple large randomized studies of the anti–tumor necrosis factor (anti-TNF) agents have been conducted with excellent safety profiles and given the successful and extensive use in systemic inflammatory diseases.

In the study by Suhler and colleagues, it appeared that 3 of 23 patients were receiving monotherapy including only infliximab and that the remainder (20) of the 23 patients were receiving some form of concurrent immunosuppression. There is evidence to suggest that concurrent treatment with antimetabolites (ie, methotrexate or azothioprine) may decrease autoantibody levels and suppresses systemic symptoms from the autoantibodies in those with systemic inflammatory diseases.^{2 - 4} The use of another immunosuppressive agent such as methotrexate along with infliximab may suppress the clinical manifestations of anti-TNF–induced lupus syndromes.⁴ Also, when these autoantibodies are found, they rarely cause severe systemic disease. The rationale for this effect may be that the autoantibodies engendered by the anti-TNF therapy are IgM and are less pathogenic than IgG typically found in systemic lupus.³ It would be interesting to note whether those treated only with monotherapy or those with concurrent immunosuppression including only prednisone were associated with the adverse events, such as systemic signs of lupus, that were mentioned.

Also, anti-TNF agents have been shown to be more effective in decreasing disease progression in rheumatoid arthritis when used in combination with a second immunosuppressive agent (ie, methotrexate) than either agent alone as studied in the prospective randomized multicentered Trial of Etanercept and Methotrexate With Radiographic Patient Outcomes.⁵ Based on this experience, the most effective treatment in systemic disease may be the optimal approach for ocular disease both from an efficacy standpoint and to prevent adverse effects.

Consideration may also be given to the testing of anticardiolipin antibodies in patients undergoing treatment with anti-TNF agents in light of the patient who had the pulmonary embolism and the known association of infliximab and etanercept with anticardiolipin antibody positivity.⁶ Testing for anticardiolipin antibodies should likely be considered as part the standard workup and monitoring for the anti-TNF agents, especially in those cases that develop thromboembolic events.

Overall, we applaud Suhler and colleagues for their excellent work in increasing our knowledge of infliximab treatment for cases of uveitis and for describing possible complications of the therapy. Given the widespread use of anti-TNF agents and their significant effectiveness against many inflammatory diseases, including significant benefit for patients with uveitis, we feel that this article should be carefully considered but not used as evidence to eliminate infliximab for the treatment of uveitis.

Correspondence: Dr Mandava, Rocky Mountain Lions Eye Institute, University of Colorado School of Medicine, 1675 N Ursula St, Aurora, CO 80045 (naresh.mandava@uchsc.edu).

Financial Disclosure: None reported.