Golimumab (GLM), A New Human Anti-TNF-alpha Monoclonal Antibody, Administered Subcutaneously Every 4 Weeks in Methotrexate-Naïve Patients with Active Rheumatoid Arthritis: Week 24 Results of the Randomized, Double-Blind, Placebo-Controlled, GO-BEFORE Study

초록

Objective: To assess the efficacy and safety of every 4 weeks subcutaneous administration of golimumab (GLM) alone or in combination with MTX versus MTX alone in MTX naïve patients with active rheumatoid arthritis (RA). Methods: In this multicenter, randomized, double-blind, placebo-controlled study, adult patients with active RA ( 4 tender and 4 swollen joints) who were MTX-naïve were randomly assigned to receive placebo (PBO) injections q4weeks plus MTX up to 20 mg per week, GLM 100 mg injections q4weeks plus PBO capsules, GLM 50 or 100 mg injections q4 weeks plus MTX up to 20 mg per week. Co-primary endpoints were the proportion of patients with  50% improvement in American College of Rheumatology Response criteria (ACR 50) at week 24 and change from baseline in Sharp score (van der Heijde modification) at week 52 (to be completed). For the primary endpoint analysis, all randomized patients were to be included (Intent To Treat analysis, ITT), and the pre-specified hierarchical statistical test procedure was used to compare the combined GLM 50 mg + MTX and GLM 100 mg + MTX with PBO + MTX first and, if this test was significant at 0.05 level, a pairwise comparison between GLM 50 or 100 mg + MTX and PBO + MTX would be performed. If the test is positive the non-inferiority comparison between GLM alone and MTX alone would be performed. Data through week 24 are presented. Results: Demographic and efficacy results of 637 enrolled patients are summarized in the table. The primary endpoint was not met. Three patients who were randomly assigned to treatment but withdrew consent and discontinued study before receiving any treatment with study agent were included in the pre-specified ITT analyses as nonresponders. A post-hoc, modified intention-to-treat (mITT) analysis excluding these 3 patients for the primary endpoint was also performed. In this mITT analysis, ACR 50 responses were statistically significantly higher in the GLM 50 m