Successful discontinuation of biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis in real-world settings

Abstract

Objectives

To analyze the proportion of successful biological disease-modifying antirheumatic drugs (bDMARDs) discontinuation and related factors in patients with rheumatoid arthritis (RA) in clinical settings.

Methods

Among 1775 RA patients who started bDMARDs between 2003 and 2012, 43 patients with DAS28-ESR <3.2 at the time of bDMARD discontinuation were extracted. Patients were divided into two groups (bio-free success: BS and bio-free failure: BF groups) based on bDMARD usage and disease activity 1 year after discontinuation. We evaluated the proportion of bio-free success and assessed factors related to bio-free success.

Results

Twenty-five patients (58.1%: BS group) maintained discontinuation of bDMARDs and DAS28-ESR <3.2 at 1 year after discontinuation. The median DAS28-ESR at bDMARD initiation was lower in the BS group than in the BF group (3.95 vs 5.04; p = .04). The BS group experienced a larger decrease in average glucocorticoid (GC) dose during bDMARD use than the BF group (−3.0 mg/day vs 0 mg/day; p = .01).

Conclusion

bDMARDs were discontinued without flare up of RA in 58.1% of patients with RA in clinical settings. A lower DAS28-ESR at initiation and reduction of GC dose before discontinuation of bDMARD were important factors associated with bio-free success.

Keywords:

• Biological disease-modifying antirheumatic drugs
• discontinuation
• drug-free
• glucocorticoids
• rheumatoid arthritis

Acknowledgements

We thank all patients in the IORRA database, and all members of the Institute of Rheumatology, Tokyo Women’s Medical University Hospital for the successful management of the IORRA study cohort. We also would like to thank Editage (www.editage.com) for English language editing.

Conflict of interest

The IORRA (Institute of Rheumatology, Rheumatoid Arthritis) database has been supported by an unrestricted grant from 23 pharmaceutical companies: Asahi Kasei Pharma Co., Astellas Pharma Inc., AbbVie Japan GK, Ayumi Pharmaceutical Co., Eisai Co., Ltd., Kaken Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Kyowa Pharma Chemical Co., Ltd., Sekisui Medical Co., Ltd., Taisho Pharma Co., Ltd., Daiichi Sankyo Co, Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Chugai Pharmaceutical Co., Ltd., Teijin Pharma, Ltd., Torii Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Nippon Kayaku Co., Ltd., Japan Tobacco Inc., Pfizer Japan Inc., Bristol-Myers Squibb Company, Mochida Pharmaceutical Co., Ltd., and UCB Japan Co. Ltd.

Moeko Ochiai has no conflicts of interest to declare. Eiichi Tanaka has received lecture fees or consulting fees from AbbVie Japan GK, Asahi Kasei Pharma Co., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kyowa Pharma Chemical Co., Ltd., Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma, Ltd. Eri Sato has no conflicts of interest to declare. Eisuke Inoue has received speaker fee from Bristol Myers Squibb Co., Ltd. and Pfizer Japan Inc. Mai Abe has no conflicts of interest to declare. Kumiko Saka has no conflicts of interest to declare. Eri Sugano has no conflicts of interest to declare. Naohiro Sugitani has no conflicts of interest to declare. Yoko Higuchi has no conflicts of interest to declare. Rei Yamaguchi has no conflicts of interest to declare. Naoki Sugimoto has no conflicts of interest to declare. Katsunori Ikari has received speaker’s fee from Asahi Kasei Pharma Co., Astellas Pharma Inc., AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Kaken Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., Teijin Pharma, Ltd., and UCB Japan Co. Ltd. Ayako Nakajima has received research grants from Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc. AN has received speaker’s fees from AbbVie Japan GK, Actelion Pharmaceuticals Japan, Ltd., Asahi Kasei Pharma Co., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., and Hisamitsu Pharmaceutical Co. Inc., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., and Teijin Pharma, Ltd. AN has received consultant fees from Nippon Kayaku Co., Ltd. Hisashi Yamanaka has received speaker fees from Astellas Pharma Inc., Bristol Myers Squibb Co., Ltd., Pfizer Japan Inc., Mitsubishi Tanabe Pharma Co., Teijin Pharma, Ltd. and YL Biologics, Ltd. Masayoshi Harigai has received research grants from AbbVie Japan GK, Asahi Kasei Pharma Co., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi & Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma, Ltd. MH has received speaker’s fee from AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma, Ltd. MH is a consultant for AbbVie Japan GK, Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb Co., Ltd., Kissei Pharmaceutical Co., Ltd. and Teijin Pharma, Ltd.