TREATMENT OF RHEUMATOID-ARTHRITIS WITH ORAL TYPE-II COLLAGEN - RESULTS OF A MULTICENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Objective. Oral administration of cartilage-derived type II collagen ( CII) has been shown to ameliorate arthritis in animal models of joint inflammation, and preliminary studies hare suggested that this novel t herapy is clinically beneficial and safe in patients with rheumatoid a rthritis (RA). The present study was undertaken to test the safety and efficacy of 4 different dosages of orally administered CII in patient s with RA. Methods. Two hundred seventy-four patients with active RA w ere enrolled at 6 different sites and randomized to receive placebo or 1 of 4 dosages (20, 100, 500, or 2,500 mu g/day) of oral CII for 24 w eeks. Efficacy parameters were assessed monthly, Cumulative response r ates (percentage of patients meeting the criteria for response at any time during the study) were analyzed utilizing 3 sets of composite cri teria: the Paulus criteria, the American College of Rheumatology crite ria for improvement in RA, and a requirement for greater than or equal to 30% reduction in both swollen and tender joint counts. Results. Ei ghty-three percent of patients completed 24 weeks of treatment. Numeri c trends in favor of the 20 mu g/day treatment group were seen with al l 3 cumulative composite measures. However, a statistically significan t increase (P = 0.035) in response rate for the 20 mu g/day group vers us placebo was detected using only the Paulus criteria. The presence o f serum antibodies to CII at baseline was significantly associated wit h an increased likelihood of responding to treatment. No treatment-rel ated adverse events were detected. The efficacy seen with the lowest d osage is consistent with the findings of animal studies and with known mechanisms of oral tolerance in which lower doses of orally administe red autoantigens preferentially induce disease-suppressing regulatory cells. Conclusion. Positive effects were observed with CII at the lowe st dosage tested, and the presence of serum antibodies to CII at basel ine may predict response to therapy. No side effects were associated w ith this novel therapeutic agent, further controlled studies are requi red to assess the efficacy of this treatment approach.