Drug retention rates of second biologic agents after switching from tumor necrosis factor inhibitors for rheumatoid arthritis in Japanese patients on low-dose methotrexate or without methotrexate

Abstract

Objectives. The purpose of this study was to explore drug retention rates of second biologic agents after switching from tumor necrosis factor inhibitors (TNFi) in clinical practice in patients with rheumatoid arthritis (RA) on low-dose methotrexate (MTX) or without MTX.

Methods. A total of 169 RA patients who had been withdrawn from first-course TNFi therapy and received a different TNFi or tocilizumab (TCZ) as a second biologic agent were selected from the Tsurumai Biologics Communication Registry, an observational cohort database. Retention rates of second biologic treatment were compared by the type of first TNFi and second biologic agents.

Results. Eighty-six patients received first-course infliximab (IFX) or adalimumab (ADA) therapy, and 83 patients received first-course etanercept (ETN) therapy. The former group had a significantly higher retention rate (IFX, 81.1%; ADA, 83.3%) of the second biologic therapy compared to the latter (56.6%, p < 0.001, log-rank test). Drug retention rates of the second biologic agent after switching from IFX/ADA were significantly higher with ETN (90.0%) and TCZ (94.7%) than with ADA/IFX (59.3%). Drug retention rates of the second biologic agent after switching from ETN were significantly higher with TCZ (75.9%) than with ADA/IFX (46.3%). The differences were significant even after adjusting for baseline clinical variables using the Cox proportional hazards model.

Conclusions. Drug retention rates of IFX and ADA after switching from the first TNFi were significantly lower compared to those of ETN and TCZ in patients on low-dose MTX or without MTX.

Keywords:

• Rheumatoid arthritis
• Methotrexate
• TNF inhibitor
• Tocilizumab
• Second-line drug

Acknowledgments

We gratefully acknowledge the assistance of the following physicians at TBC-affiliated institutions for providing valuable data to this multicenter research study and thank them for their kind suggestions: Dr. Toshihisa Kanamono (Department of Orthopedic Surgery, Nagano Red Cross Hospital, Nagano, Japan), Dr. Yukiyoshi Ohishi (Department of Rheumatology, Toyohashi Municipal Hospital, Toyohashi, Japan), Dr. Yoshito Etoh (Department of Orthopedic Surgery, Higashi Nagoya National Hospital, Nagoya, Japan), Dr. Masahiro Kobayakawa (Department of Orthopedic Surgery, Fukuroi Municipal Hospital, Fukuroi, Japan), Dr. Naoki Fukaya (Department of Orthopedic Surgery, Kariya Toyota General Hospital, Kariya, Japan), Dr. Seiji Tsuboi (Department of Orthopedic Surgery, Shizuoka Kosei Hospital, Shizuoka, Japan), Dr. Takefumi Kato (Kato Orthopedic Surgery, Okazaki, Japan), Dr. Hideki Takagi (Department of Orthopedic Surgery, Nagoya Central Hospital, Nagoya, Japan), Dr. Takeshi Oguchi (Department of Orthopedic Surgery, Anjo Kosei Hospital, Anjo, Japan), and Dr. Takayoshi Fujibayashi (Department of Orthopedic Surgery, Konan Kosei Hospital, Konan, Japan).

Conflicts of interest

N. Ishiguro received grants and lecture fees from Daiichi Sankyo Company, Ltd., Takeda Pharmaceutical Co., Ltd., Hisamitsu Pharmaceutical Co., Inc., Otsuka Pharmaceutical Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Kaken Pharmaceutical Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Bristol-Myers Squibb, Abbvie Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, Inc., and Pfizer Japan, Inc.

T. Kojima received lecture fees from Mitsubishi Tanabe Pharmaceutical, Takeda Pharmaceutical Co., Ltd., Eisai Pharmaceutical Co., Abbvie Inc., Bristol-Myers Squibb, Pfizer Japan, Inc., and Chugai Pharmaceutical Co., Ltd., and research grants from Takeda Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., and Astellas Pharma, Inc.

A. Kaneko and Y. Hirano received lecture fees from Abbvie Inc., Eisai Pharmaceutical Co., Mitsubishi Tanabe Pharmaceutical, Takeda Pharmaceutical Co., Ltd., Pfizer Japan, Inc., Chugai Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., UCB Co., Ltd., and Bristol-Myers Squibb.

All other authors have no conflicts of interest to declare.