POS0664 A MULTICENTER RANDOMIZED STUDY IN RHEUMATOID ARTHRITIS TO COMPARE IGURATIMOD, METHOTREXATE, OR COMBINATION: 52 WEEK EFFICACY AND SAFETY RESULTS OF THE SMILE TRIAL

Background: Iguratimod (IGU) has demonstrated efficacy and safety for active rheumatoid arthritis (RA) patients in double-blind clinical trials in China and Japan as a new disease-modifying anti-rheumatic drug (DMARD). There are no studies evaluating the radiographic progression of structural joint damage of IGU for the treatment of RA using the mTSS as the primary endpoint. Objectives: Our study was to evaluate the efficacy and safety of IGU monotherapy and IGU combined methotrexate (MTX) compared with MTX monotherapy, including the inhibitory effects of joint destruction. Methods: This randomized, double-blind, parallel-controlled, multicenter study in patients with active RA who have not previously used MTX and biological DMARDs (bDMARDs) (ClinicalTrials.gov Identifier NCT01548001 ) was carried out in China. Patients were randomized 1:1:1 to receive IGU 25 mg twice a day (bid), MTX 10mg once a week(qw) for the first 4 weeks and 15 mg once a week(qw) for week 5 to 52, or IGU combined MTX (IGU+MTX) for 52 weeks. The primary endpoints were to assess and compare American College of Rheumatology 20% (ACR20) response and the change of modified total Sharp scoring (mTSS) score over 52 weeks (Intention-to-treat, ITT analysis). The non-inferiority test was used to analyze the difference of ACR20 response at 52 weeks between the IGU monotherapy and the MTX monotherapy arms, and the non-inferiority limit value was 10%. The difference test was used for the comparison between the IGU+MTX and MTX monotherapy arms. Two-way ANOVA was used to analyze the difference of the changes of mTSS score of each arm compared with baseline value (0 week). Results: A total of 895 patients were randomized to IGU 25mg bid (n =297), MTX 10-15mg qw(n=293), and IGU+MTX (n=305). Baseline characteristics were comparable between the arms (Table 1). Table 1. Demographic and Other Baseline Characteristics (SAS) IGU MTX IGU+MTX Number of Subjects 297 293 305 Age, mean (SD) years 46.87(10.67) 47.63(10.70) 48.37(10.69) Female/male, % 77.44/22.56 ...