Background Iguratimod (IGU) is a small-molecule disease-modifying antirheumatic drug (DMARD) that has been shown to suppress inflammation via the inhibition of nuclear factor-kappa B activation in vitro. The efficacy of combination therapy with IGU and methotrexate (MTX) has been demonstrated in comparison with that of placebo in rheumatoid arthritis (RA). However, its efficacy in comparison with other DMARDs such as sulfasalazine (SSZ) has not been elucidated.
Objectives To clarify the efficacy of combination therapy with IGU in comparison with that of SSZ with MTX in typical clinical practice.
Methods We analyzed data from 16,825 RA patients registered in a large database (NinJa: National Database of Rheumatic Diseases by iR-net in Japan) from April 2011 to March 2015 (1). In this study, we compared the two groups who received IGU or SSZ in addition to methotrexate in the earlier year. We excluded patients who started receiving biologic DMARDs, and IGU or SSZ the year prior to the study period, and those whose regimens were changed to other DMARDs such as tacrolimus and bucillamine. Baseline characteristics were compared using the t test, Wilcoxon test, or chi-square test. Fisher analysis was conducted for both outcomes. The predicted probability of IGU treatment was calculated by fitting a logistic regression model using all clinically relevant variables as presented in Table 1. Moreover, to reduce the effect of treatment-selection bias and potential confounding in this observational study, we performed rigorous adjustment for significant differences in the baseline characteristics of patients with propensity-score matching using the following algorithm: 1:1 optimal match with a ±0.15 caliper and no replacement. We used the standardized difference to measure covariate balance, whereby a standardized mean difference of >0.1 represents meaningful imbalance. The outcome was remission rate with disease activity score 28 CRP (DAS28-CRP) in the year after initiation of IGU or SSZ therapy.
Results The group that received IGU in addition to MTX included 66 patients; the other group that received SSZ in addition to MTX included 163 patients. Table 1 shows the results of the pre- and post-propensity score matching of patients' characteristics. Sixty-five patients were compared in each group after score matching. The remission rates of DAS28-CRP in the following year was 77.2% (44/57 patients) and 71.7% (38/53 patients; P=0.52) in the IGU and SSZ groups, respectively.
Conclusions Combination therapy with IGU or SSZ and methotrexate for rheumatoid arthritis did not show a significant difference in disease activity. Further studies are needed.
Matsui T, Kuga Y, Kaneko A, et al. Disease Activity Score 28 (DAS28) using C-reactive protein underestimates disease activity and overestimates EULAR response criteria compared with DAS28 using erythrocyte sedimentation rate in a large observational cohort of rheumatoid arthritis patients in Japan. Ann Rheum Dis. 2007;66(9):1221–6.
Acknowledgements NinJa has been supported in part by a research grant from the Health and Labor Sciences, funded by the Ministry of Health, Labor, and Welfare of Japan.
Disclosure of Interest K. Tokunaga Paid instructor for: AbbVie, Eisai Co. Ltd., and Mitsubishi Tanabe Pharma, A. Shiraishi Paid instructor for: Chugai Pharmaceutical Co., Ltd., H. Oshikawa: None declared, N. Hagino Grant/research support from: Mitsubishi Tanabe Pharma, Chugai Pharmaceutical Co. Ltd., and Bristol Meyers Squibb, Paid instructor for: Santen Pharmaceutical Co. Ltd. and Takeda Pharmaceutical Co. Ltd., J. Nishino: None declared, S. Tohma Grant/research support from: Pfizer Japan Inc., Eisai Co., Ltd., and Chugai Pharmaceutical Co. Ltd.