Drug retention rates and relevant risk factors for drug discontinuation due to adverse events in rheumatoid arthritis patients receiving anticytokine therapy with different target molecules

Ryoko Sakai, Michi Tanaka, Toshihiro Nanki, Kaori Watanabe, Hayato Yamazaki, Ryuji Koike, Hayato Nagasawa, Koichi Amano, Kazuyoshi Saito, Yoshiya Tanaka, Satoshi Ito, Takayuki Sumida, Atsushi Ihata, Yoshiaki Ishigatsubo, Tatsuya Atsumi, Takao Koike, Atsuo Nakajima, Naoto Tamura, Takao Fujii, Hiroaki Dobashi, Shigeto Tohma, Takahiko Sugihara, Yukitaka Ueki, Akira Hashiramoto, Atsushi Kawakami, Noboru Hagino, Nobuyuki Miyasaka, Masayoshi Harigai
Annals of the Rheumatic Diseases 2012, 71 (11): 1820-6

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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