Background Abatacept (ABT), a selective T-cell co-stimulation modulator, is a new biologic drug and has been available for rheumatoid arthritis (RA) patients since 2010 in Japan. We have previously reported that concomitant methotrexate (MTX) therapy did not significantly affect the clinical efficacy of ABT [1, 2] using data from our multicenter registry system.
Objectives The aim of this study is to confirm whether our initial finding is correct by using propensity score matching analysis.
Methods Participants were 419 patients with RA who were prospectively registered in the Tsurumai Biologics Communication Registry, treated with ABT, and followed up for at least 52 weeks. In this study, the probability score was estimated using a multivariate logistic regression model predicting concomitant use of MTX versus no concomitant use of MTX using the following variables: age, gender, disease duration, dose of ABT (mg/kg), concomitant use of PSL, Steinbrocker's stage, history of previous biological DMARDs therapy, disease activity at baseline (DAS28-CRP, mHAQ score, ESR, and MMP-3). Greedy propensity score matching was implemented (1:1 matching using a caliper of 0.01). The last observation carried forward (LOCF) method was used in each analysis. Survival analysis was performed with the Kaplan-Meier method and the log-rank test.
Results Unadjusted analysis consisted of 217 and 202 patients treated with and without concomitant MTX treatment, respectively. The propensity score adjusted analysis consisted of 52 patients each. Unadjusted analysis demonstrated that the mean DAS28-CRP score in the patients with MTX was significantly lower than that in the patients without MTX at 4, 12, and 52 weeks (2.83 vs 3.27, p<0.01), while there was no difference at baseline (Fig. 1a). Additionally, significantly higher proportion of the patients achieved low disease activity (LDA) at 4, 12, and 52 weeks (p<0.01) in the patients with concomitant MTX (Fig. 1b). The adjusted analysis demonstrated there was no significant difference in the mean DAS28-CRP score (Fig. 2a) and also the categorical distribution of disease activity between the groups (Fig. 2b). The long-term retention rate was similar between the patients with and those without concomitant MTX throughout 4 years (Fig. 1c, 2c).
Conclusions Unadjusted analysis using greater number of patients compared to our previous study apparently showed the augmenting effect of concomitant MTX usage for the short-term clinical efficacy of ABT. However, the analysis with careful adjustment using propensity score matching clearly revealed that the augmenting effect of concomitant MTX on the ABT efficacy was practically limited. The long-term retention rate was quite similar even in the unadjusted analysis. We suggest that we can expect the adequate clinical efficacy of ABT therapy even in the patients taking no MTX concomitantly.
Takahashi N, et al. Clinical efficacy of abatacept in Japanese rheumatoid arthritis patients. Mod Rheumatol 2013;23:904.
Takahashi, et al. Use of a 12-week observational period for predicting low disease activity at 52 weeks in RA patients treated with abatacept: a retrospective observational study based on data from a Japanese multicenter registry study. Rheumatology (Oxford) 2014. in press
Disclosure of Interest N. Takahashi: None declared, T. Kojima Speakers bureau: Abbvie Japan Co. Ltd, Eisai Co. Ltd, UCB Japan Co. Ltd, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Ltd, Pfizer Co. Ltd, Chugai Pharmaceutical Co. Ltd, Janssen Pharmaceutical K.K., and Bristol-Myers Squibb Co. Ltd., K. Funahashi Speakers bureau: Abbvie Japan Co. Ltd, Eisai Co. Ltd, UCB Japan Co. Ltd, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Ltd, Pfizer Co. Ltd, Chugai Pharmaceutical Co. Ltd, Janssen Pharmaceutical K.K., and Bristol-Myers Squibb Co. Ltd., N. Ishiguro Grant/research support from: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Taisho Toyama Pharmaceutical, Kaken Pharmaceutical, Eisai, Janssen Pharmaceuticals, Bristol-Myers Squibb, Abbott Japan, Chugai Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, and Pfizer Japan, Speakers bureau: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Taisho Toyama Pharmaceutical, Kaken Pharmaceutical, Eisai, Janssen Pharmaceuticals, Bristol-Myers Squibb, Abbott Japan, Chugai Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, and Pfizer Japan