POS0664 A MULTICENTER RANDOMIZED STUDY IN RHEUMATOID ARTHRITIS TO COMPARE IGURATIMOD, METHOTREXATE, OR COMBINATION: 52 WEEK EFFICACY AND SAFETY RESULTS OF THE SMILE TRIAL
Authors: F. Du, J. Xu, X. Li, Z. Li, X. Li, X. Zuo, L. Bi, D. Zhao, M. Zhang, H. Wu, D. He, Z. Wu, Z. Li, Y. Li, J. Xu, Y. Tao, J. Zhao, J. Chen, H. Zhang, J. Li, L. Jiang, Z. Xiao, Z. Chen, G. Yin, L. Gong, G. Wang, L. Dong, W. Xiao, C. Bao
Journal: Annals of the Rheumatic Diseases (2021)

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 79.18/20.82 78.03/21.97 Duration of RA, mean(SD) years 11.67±7.16 11.60±7.98 11.67±7.27 CRP, mean(SD) mg/L 2 22.32±35.47 20.67±26.61 19.74±31.38 Tender joint count, mean (SD) 14.59±9.16 14.83±9.30 14.93±9.88 Swollen joint count, mean (SD) 9.81±6.63 9.73±7.20 9.51±6.22 DAS28-CRP, mean (SD) 5.084±0.994 5.102±0.979 5.103±0.956 HAQ score, mean (SD) 15.82±11.25 15.24±10.93 16.06±10.92 SAS: Safety Analysis Set; CRP: C-reactive protein; DAS28: disease activity score; HAQ: Health Assessment Questionnaire The study met its primary endpoints. More concretely, IGU monotherapy and IGU+MTX were found to be superior to MTX at week 52 with a higher ACR20 response of 77.44%(230/297, P=0.0019) and 77.05%(235/305, P=0.0028) versus 65.87%(193/293) (fig 1). As shown in fig 1, the structural remission (ΔmTSS≤0.5) was statistically significant for IGU monotherapy (57.4%, P=0.0308) but not for IGU+MTX arm (55%) versus MTX monotherapy (47.8%). Overall incidence of the adverse events (AEs) leading to study discontinuation were reported in 13.8% (41/297) in IGU monotherapy arm, 11.26% (33/293) in MTX monotherapy arm and 11.51% (35/305) patients in IGU+MTX arm. The incidence of adverse drug reactions (ADR) leading to study discontinuation were 11.45% (34/297), 8.53% (25/293) and 9.21% (28/305), respectively. There was no one death and no significant difference in all the safety indicators among the three arms. Conclusion: Iguratimod alone or in combination with MTX demonstrated superior efficacy with acceptable safety compared to MTX for patients with active RA who have not previously used MTX bDMARDs. Disclosure of Interests: None declared