Safety and effectiveness of 24-week treatment with iguratimod, a new oral disease-modifying antirheumatic drug, for patients with rheumatoid arthritis: interim analysis of a post-marketing surveillance study of 2679 patients in Japan

Abstract

Objective: To determine the real-world safety and effectiveness of iguratimod (IGU) for rheumatoid arthritis (RA), a 52-week, Japanese, post-marketing surveillance study was conducted. An interim analysis at week 24 was performed.

Methods: This study included all RA patients who received IGU following its introduction to the market. All adverse events (AEs) and adverse drug reactions (ADRs) were collected. Effectiveness was evaluated by the change in Disease Activity Score 28-C-reactive protein (DAS28-CRP) from baseline to week 24.

Results: Safety was analyzed in 2679 patients. The overall incidences of AEs, ADRs, and serious ADRs were 38.41, 31.65, and 3.21%, respectively; the most commonly reported serious ADRs were pneumonia/bacterial pneumonia, interstitial lung disease, and Pneumocystis jiroveci pneumonia. Concomitant glucocorticoid use and comorbid conditions associated with respiratory disease were identified as risk factors for serious infections. Pulmonary alveolar hemorrhage and increased international normalized ratio of prothrombin time were observed with concomitant use of IGU and warfarin. The DAS28-CRP decreased from baseline to week 24.

Conclusion: Although a safety concern was identified with concomitant use of IGU and warfarin, this real-world study showed no other new safety concerns and similar effectiveness to clinical trials. IGU is a new therapeutic option for RA patients.

Keywords:

• Iguratimod
• Post-marketing surveillance
• Rheumatoid arthritis
• Safety

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Erratum

Acknowledgments

The authors would like to thank Stacey Tobin, PhD, of Edanz Group Japan K.K. for providing medical writing services. The authors are grateful to Dr Kazuhiko Yamamoto, as a medical expert, for his contribution, as well as to all those who collaborated with us for this surveillance. We also thank our safety advisers Dr Arata Azuma, Dr Yohko Kawai, and Dr Atsushi Tanaka for their useful advice.

Conflict of interest

T. Mimori received research grants or speaker’s fees from Astellas Pharma Inc., Actelion Pharmaceuticals Japan Ltd., Ayumi Pharmaceutical Corp., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., and Mitsubishi Tanabe Pharma Corp. M. Harigai received consultancy fees, honoraria, or research grants from AbbVie G.K., Astellas Pharma Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corp., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and UCB Japan Co., Ltd. T. Atsumi received honoraria for educational meetings from Mitsubishi Tanabe Pharma Corp., Chugai Pharmaceutical Co., Ltd., Astellas Pharma Inc., Takeda Pharmaceutical Co., Ltd., Pfizer Inc., AbbVie G.K., and Eisai Co. Ltd., and has received a research grant from Astellas Pharma Inc., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corp., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co. Ltd., Otsuka Pharmaceutical Co., Ltd. and Pfizer Inc. T. Fujii belongs to a department that is financially supported by 4 pharmaceutical companies (Mitsubishi Tanabe Pharma Corp., Chugai Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K., and Eisai Co., Ltd.) and received honoraria (lecture fee) from Bristol-Myers Squibb K.K., Ono Pharmaceutical Co., Ltd. and Pfizer Japan Inc., and grant/research funding from AbbVie G.K., Pfizer Japan Inc., Astellas Pharma Inc., Takeda Pharmaceutical Co., Santen Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Ono Pharmaceutical Co., Ltd., and UCB Japan Co., Ltd. M. Kuwana received research grants or speaker’s fees from Pfizer Japan Inc., Ono Pharmaceutical Co., Ltd, Janssen Pharmaceutical K.K., Chugai Pharmaceutical Co., Ltd., Astellas Pharma Inc., Ayumi Pharmaceuticals Corp., Eisai Co., Ltd., AbbVie G.K., and Mitsubishi Tanabe Pharma Corp. H. Matsuno has received speaker fees from Daiichi Sankyo Co. Ltd. and consulting and speaker fees from Ayumi Pharmaceutical Corp. S. Momohara has declared no conflicts of interest. S. Takei has received grants from Chugai Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corp., and Eisai Co., Ltd.; lecture fees from Chugai Pharmaceutical Co., Ltd., Tanabe Pharma, Japan Blood Products Organization, Pfizer Pharmaceutical Co. Ltd., and AbbVie G.K., and consulting fees from Daiichi Sankyo Co. Ltd. N. Tamura has received research grants from AbbVie G.K., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Ayumi Pharmaceuticals Corp., and Takeda Pharmaceutical Co., Ltd. Y. Takasaki has received speaker fees or honoraria from Mitsubishi Tanabe Pharma Corp. and Chugai Pharmaceutical Co. Ltd. S. Ikeuchi is an employee of Eisai Co., Ltd. S. Kushimoto is an employee of Toyama Chemical Co., Ltd. T. Koike has received speaker fees from AbbVie G.K. and Mitsubishi Tanabe Pharma Corp. and honoraria from Bristol-Myers Squibb K.K. for research grant reviews.