Safety and effectiveness of iguratimod in patients with rheumatoid arthritis: Final report of a 52-week, multicenter postmarketing surveillance study

Abstract

Objectives: We evaluated the long-term (52 weeks) safety and effectiveness of iguratimod (IGU) in patients with rheumatoid arthritis (RA).

Methods: This multicenter, prospective, observational study included all evaluable RA patients who received IGU since its market launch in 2012. We evaluated adverse events (AEs); adverse drug reactions (ADRs); ADRs of special interest, including liver and renal dysfunctions, interstitial lung disease, gastrointestinal and blood disorders, and infection; and change in Disease Activity Score 28-C-reactive protein (DAS28-CRP) at week 52.

Results: Safety and effectiveness were analyzed in 2666 and 1614 patients, respectively. The incidences of AEs, serious AEs, ADRs, and serious ADRs were 46.92, 7.35, 38.26, and 4.58%, respectively. The incidence of ADRs peaked at approximately 4 weeks of treatment. Subsequently, the ADR incidence did not increase over time. Improvement of RA activity was shown up to week 52.

Conclusion: Long-term treatment with IGU in patients with RA resulted in a tolerable safety profile and an improvement in RA activity. IGU could be considered a useful treatment option for patients with RA.

Trial registration: ClinicalTrials.gov identifier: NCT01850966.

Keywords:

• Iguratimod
• long-term effects
• postmarketing surveillance study
• rheumatoid arthritis
• safety

Acknowledgments

The authors would like to thank Michelle Belanger, MD, Keyra Martinez Dunn, MD, and Hikari Chiba of Edanz Medical Writing for providing medical writing services. The authors would also like to thank all participants and physicians who participated in this study.

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, and research grants from AbbVie G.K., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corp., Nippon Kayaku Co., Ltd., Ono Pharmaceutical Co., Ltd., Taisho-Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Co., Ltd. T. Atsumi received speaker’s fees and honoraria for educational meetings from AbbVie G.K., Astellas Pharma Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corp., Pfizer Inc., Takeda Pharmaceutical Co., Ltd., and UCB Japan Co., Ltd.; and consultancy fees from Chugai Pharmaceutical Co., and UCB Japan Co., Ltd. T. Fujii received research grants and/or speaker’s fees from Pfizer Japan Inc., Ono Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Corp., Eisai Co., Ltd., AbbVie GK., and Astellas Pharma Inc. 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 Pharmaceutical Corp., Eisai Co., Ltd., AbbVie G.K., and Mitsubishi Tanabe Pharma Corp. H. Matsuno received speaker’s fees from Daiichi Sankyo Co., Ltd., and consulting and speaker’s fees from Ayumi Pharmaceutical Corp. S. Momohara belongs to a department that is financially supported by three pharmaceutical companies (Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., and NuVasive, Inc.) and received speaker’s fees from AbbVie G.K., Astellas Pharma Inc., Ayumi Pharmaceutical Corp., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corp., Ono Pharmaceutical Co., Ltd., Pfizer Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and UCB Japan Co., Ltd. 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., Mitsubishi Tanabe Pharma Corp., Japan Blood Products Organization, Pfizer Pharmaceutical Co., Ltd., and AbbVie G.K.; and consulting fees from Daiichi Sankyo Co., Ltd. N. Tamura received research grants from AbbVie G.K., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Ayumi Pharmaceutical Corp., and Takeda Pharmaceutical Co., Ltd. Y. Takasaki received speaker’s fees or honoraria from Mitsubishi Tanabe Pharma Corp., and Chugai Pharmaceutical Co., Ltd. K. Yamamoto received consultancy fees, honoraria, and research grants from AbbVie G.K., Astellas Pharma Inc., Ayumi Pharmaceutical Corp., Ltd., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corp., Ono Pharmaceutical Co., Ltd., Taisho-Toyama Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Co., Ltd. S. Ikeuchi is an employee of Eisai Co., Ltd. S. Kushimoto is an employee of Toyama Chemical Co., Ltd. T. Koike received speaker’s fees or honoraria for research grant reviews from AbbVie G.K., Astellas Pharma Inc., Ayumi Pharmaceuticals Corp., Bristol-Myers Squibb K.K. Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., GlaxoSmithKline K.K., Mitsubishi Tanabe Pharma Corp., Ono Pharmaceutical Co., Ltd, Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and UCB Japan Co., Ltd.