A Prospective Trial of Infliximab Therapy for Patients with Refractory Uveitis: Preliminary Results

Abstract

Abstract: : Purpose: Infliximab is a monoclonal antibody that neutralizes tumor necrosis factor alpha (TNF-α). It has proven utility in the treatment of several immune-mediated diseases but has not been prospectively studied in the management of uveitis. We sought to determine the efficacy of infliximab in the treatment of non-infectious uveitis in a prospective, open-label clinical trial. Methods: We have enrolled 11 patients to date, all with uveitis which was either refractory to standard immunosuppression, defined as prednisone and at least one other immunosuppressive drug, or with intolerance to such treatment. Eight females and three males, with ages ranging from 20 - 74 (mean 40.9) were enrolled. Five patients were diagnosed with idiopathic uveitis, three with Behcet's disease, and one each with birdshot chorioretinopathy, pars planitis, and sarcoidosis. All patients were treated initially with 3 - 5 mg/kg of infliximab intravenously with three loading doses over six weeks and then maintenance therapy every eight weeks. The protocol allowed a dosage escalation of the infliximab up to 10mg/kg. Other therapy, especially prednisone, was tapered as tolerated and clinically appropriate. Results: Two patients have completed one year of therapy and five others have been treated for a minimum of 10 weeks, the a priori selected endpoint for initial assessment of efficacy. All seven of these patients have responded subjectively and objectively as measured by a composite endpoint of visual acuity, intraocular inflammatory activity judged clinically and with fluoroscein angiography, and ability to taper other immunosuppressives. One patient subsequently stopped treatment after 40 weeks due to a new onset pauciarticular arthritis associated with elevated ASLO titers, possibly related to poststreptococcal disease. Conclusions: These preliminary results demonstrate great promise for the use of infliximab in the management of patients with uveitis whose disease is refractory to standard oral immunosuppression. Additional study is warranted.

Keywords: clinical (human) or epidemiologic studies: tre • immunomodulation/immunoregulation • clinical (human) or epidemiologic studies: out