title: 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.
abstract: 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).
  
  
  METHODS
  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.
authors.affiliation: Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Sakai
authors.forename: Michi
authors.initials: M
authors.lastname: Tanaka
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nanki
authors.forename: Kaori
authors.initials: K
authors.lastname: Watanabe
authors.forename: Hayato
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Ryuji
authors.initials: R
authors.lastname: Koike
authors.forename: Hayato
authors.initials: H
authors.lastname: Nagasawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Amano
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Saito
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ito
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sumida
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ihata
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ishigatsubo
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Atsumi
authors.forename: Takao
authors.initials: T
authors.lastname: Koike
authors.forename: Atsuo
authors.initials: A
authors.lastname: Nakajima
authors.forename: Naoto
authors.initials: N
authors.lastname: Tamura
authors.forename: Takao
authors.initials: T
authors.lastname: Fujii
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Dobashi
authors.forename: Shigeto
authors.initials: S
authors.lastname: Tohma
authors.forename: Takahiko
authors.initials: T
authors.lastname: Sugihara
authors.forename: Yukitaka
authors.initials: Y
authors.lastname: Ueki
authors.forename: Akira
authors.initials: A
authors.lastname: Hashiramoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawakami
authors.forename: Noboru
authors.initials: N
authors.lastname: Hagino
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyasaka
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Harigai
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects; D000069285:Infliximab; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor; D012042:Registries; D012307:Risk Factors; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D028761:Withholding Treatment
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; C502936:tocilizumab; D000068800:Etanercept