Objective To compare reasons for discontinuation and drug retention rates per reason among anticytokine therapies, infliximab, etanercept and tocilizumab, and the risk of discontinuation of biological agents due to adverse events (AE) in patients with rheumatoid arthritis (RA).
Method This prospective cohort study included Japanese RA patients who started infliximab (n=412, 636.0 patient-years (PY)), etanercept (n=442, 765.3 PY), or tocilizumab (n=168, 206.5 PY) as the first biological therapy after their enrolment in the Registry of Japanese Rheumatoid Arthritis Patients for Long-term Safety (REAL) database. Drug retention rates were calculated using the Kaplan–Meier method. To compare risks of drug discontinuation due to AE for patients treated with these biological agents, the Cox proportional hazard model was applied.
Results The authors found significant differences among the three therapeutic groups in demography, clinical status, comorbidities and usage of concomitant drugs. Development of AE was the most frequent reason for discontinuation of biological agents in the etanercept and tocilizumab groups, and the second most frequent reason in the infliximab group. Discontinuation due to good control was observed most frequently in the infliximab group. Compared with etanercept, the use of infliximab (HR 1.69; 95% CI 1.14 to 2.51) and tocilizumab (HR 1.98; 95% CI 1.04 to 3.76) was significantly associated with a higher risk of discontinuation of biological agents due to AE.
Conclusions Reasons for discontinuation are significantly different among biological agents. The use of infliximab and tocilizumab was significantly associated with treatment discontinuation due to AE compared with etanercept.
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Funding This work was supported by a grant-in-aid from the Ministry of Health, Labour and Welfare, Japan (H23-meneki-sitei-016 and H19-meneki-ippan-009 to NM, H22-meneki-ippann-001 to MH) and by a grant-in-aid for scientific research from the Japan Society for the Promotion of Science (#20390158 to MH, #19590530 to RK, and #50277141 to MT). This work was also supported by grants for pharmacovigilance research on biological agents from Abbott Laboratories, Bristol-Myers Japan, Eisai, Chugai Pharmaceutical, Mitsubishi Tanabe Pharma Corp, Takeda Pharmaceutical and Pfizer Japan (to MH), and by a grant from the Japanese Ministry of Education, Global Center of Excellence (GCOE) Program, ‘International Research Center for Molecular Science in Tooth and Bone Diseases’.
Competing interests KA has received research support from Chugai Pharmaceutical, Mitsubishi Tanabe Pharma and Astellas Pharma. YT has received consulting fees, speaking fees, and/or honoraria from Mitsubishi-Tanabe Pharma, Chugai Pharmaceutical, Eisai, Takeda Pharmaceutical, Astellas Pharma and Abbott Japan, and has received research grant support from Mitsubishi-Tanabe Pharma, Takeda Pharmaceutical, MSD KK, Pfizer Japan, Astellas Pharma, Chugai Pharmaceutical, Abbott Japan and Eisai. TF has received grant/research support from Abbott Japan, Eisai, Takeda Pharmaceutical, Mitsubishi Tanabe Pharma, Chugai Pharmaceutical, Pfizer Japan, Astellas Pharma, Bristol-Myers Squibb KK. NM has received research grants from Abbott Japan, Astellas Pharma, MSD KK, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical and Teijin Pharma. MH has received research grants from Abbott Japan, Astellas Pharma, Bristol Myers Squibb KK, Chugai Pharmaceutical, Eisai, Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma, Santen Pharmaceutical, Takeda Pharmaceutical and Pfizer Japan.
Ethics approval The REAL study was approved by the ethics committees of the Tokyo Medical and Dental University Hospital and other participating institutions.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.