ANTI-TNF ALPHA THERAPY IN CHRONIC RECURRENT INFLAMMATION OF THE ANTERIOR SEGMENT OF THE EYE IN PATIENTS RESISTANT TO STANDARD IMMUNOMODULATORY THERAPY

Background: Intraocular inflammatory diseases are a leading cause of visual impairment and blindness. Of those patients that develop recurrent or chronic anterior uveitis 23% will have a drop of vision below 20/50. The percentage of legally blind patients is 11%. Thus the treatment of these patients with chronic or recurrent uveitis still presents a quite a challenge, and additional treatment modalities are needed.Objectives: We tested the efficacy of selective anti-TNFa therapy in chronic inflammatory diseases of the anterior segment of the eye, non-responsive to or not tolerating standard antiinflammatory treatment consisting of a combined immunomodulatory and corticosteroid therapy.Methods: Nine consecutive patients suffering from a uveitis associated with a systemic disease were included in this study. Eight patients were suffering from a rheumatic disease, of these five from a spondylarthropathy, two of JIA (one Still's disease, one ANA positive oligoarthritis patient) and one patient had a necrotizing sclerouveitis in association with Wegener granulomatosis. One additional patient with a uveitis associated with tubulointerstitial nephritis (TINU syndrome) was also included. DMARD therapy was initiated at least 3 months prior to infliximab therapy. It consisted of methotrexate (MTX) in 7 patients, of which two received a combination of MTX and mycofenolate-mofetil. One patient received cylophosphamide, another patient leflunomide.Results: Recurrent episodes or a chronic uveitis despite immunomodulatory therapy was present at a mean period of 8.6±4.1 months prior to infliximab therapy. Infliximab was administered at 3mg/kg/BW at weeks 0, 2 and 6 in all but one patient, who received only one infusion due to an allergic reaction after her first one. Following anti-TNFa therapy the mean duration of the uveitis till remission was achieved was 12.6±11.7 days in HLA B27 positive uveitis patients, while in the JIA patients 38.5±3.5 days were needed. In the Wegener's patient the time to remission was 3 months. No effect of the infliximab therapy was seen in the TINU patient. Patients with HLA B27 associated uveitis remained in remission for an average of 5.5±0.5 months. This 5.5 months duration of response was similarly achieved after re-treatment of these patients. In the JIA patients the antiinflammatory effect of TNFa blockage was much more moderate and only transient. In the patient suffering from Still's disease the uveitis reactivated despite increasing doses of infiliximab after 30 weeks and in the patients with the oligoarthritis the remission of uveitis after three infliximab infusions lasted only 5 for weeks.Conclusion: HLA B27 associated uveitis as well as the sclero-uveitis in the patient suffering from Wegener's granulomatosis responded very well to infliximab therapy. In all of these patients a sustained antiinflammatory effect was achieved using anti-TNFa therapy. This is in accordance to the described positive effect anti-TNFa therapy showed in systemic manifestations of spondylarthropathies and Wegener's granulomatosis. However in both patients suffering from a chronic uveitis in association with JIA, the antiinflammatory effect of infliximab to the eyes was not sustained and was lost despite adjustment of the dose.1. El-Shabrawi Y, Hermann J. Anti-tumor necrosis factor-alpha therapy with infliximab as an alternative to corticosteroids in the treatment of human leukocyte antigen B27-associated acute anterior uveitis. Ophthalmology. 2002;109(12):2342-6; 2. El-Shabrawi Y, Hermann J. Case series of selective anti-tumor necrosis factor alpha therapy using infliximab in patients with nonresponsive chronic HLA-B27-associated anterior uveitis. Arthritis Rheum. 2002;46(10):2821-2;; 3. Brandt J et al. Infliximab treatment of severe ankylosing spondylitis: one-year followup. Arthritis Rheum. 2001 Dec;44(12):2936-7.Citation: , volume , supplement , year 2003, page Session: Miscellaneous rheumatic diseases