title: Risk for malignancy in rheumatoid arthritis patients treated with biological disease-modifying antirheumatic drugs compared to the general population: A nationwide cohort study in Japan.
abstract: OBJECTIVE
  To investigate and compare the risk for malignancy in rheumatoid arthritis (RA) patients treated with biologics in Japan to the general population.
  
  
  METHODS
  Data for 14,440 patients from 335 institutions who were given infliximab, etanercept, adalimumab, golimumab, tocilizumab, or abatacept were retrieved from the SafEty of biologics in Clinical Use in Japanese patients with RhEumatoid arthritis (SECURE) database.
  
  
  RESULTS
  We identified 333 incidents of malignancies in 320 patients during 49,320 patient-years (PY). The age- and sex-standardized incidence rate (ASR) (95% confidence interval [CI]) for overall malignancy of the SECURE cohort was 313.9/10(5) PY (271.4-361.3), and the standardized incidence rate ratio (SIR) (95% CI) was 0.745 (0.667-0.826). The ASR was decreased compared to the estimated incidence rate of malignancies in the Japanese general population (462.4/10(5) PY). The SIRs for site-specific nonhematopoietic malignancies of the SECURE cohort were not significantly elevated compared to the Japanese general population. A significant increase of SIR for malignant lymphoma (6.183, 95% CI, 4.809-7.643) was found in the SECURE cohort, similar to or slightly higher than the SIR previously reported from Japanese cohorts for RA patients.
  
  
  CONCLUSIONS
  Continued vigilance with larger numbers of patients, longer observation periods, and inclusion of different biologics are recommended.
authors.affiliation: a Department of Pharmacovigilance and.|b Department of Rheumatology Graduate School of Medical and Dental Sciences , Tokyo Medical and Dental University , Tokyo , Japan .
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Harigai
authors.affiliation: a Department of Pharmacovigilance and.|b Department of Rheumatology Graduate School of Medical and Dental Sciences , Tokyo Medical and Dental University , Tokyo , Japan .
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nanki
authors.affiliation: a Department of Pharmacovigilance and.|b Department of Rheumatology Graduate School of Medical and Dental Sciences , Tokyo Medical and Dental University , Tokyo , Japan .|c Clinical Research Center , Tokyo Medical and Dental University Hospital , Tokyo , Japan , and.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Koike
authors.affiliation: a Department of Pharmacovigilance and.|b Department of Rheumatology Graduate School of Medical and Dental Sciences , Tokyo Medical and Dental University , Tokyo , Japan .
authors.forename: Michi
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: a Department of Pharmacovigilance and.|b Department of Rheumatology Graduate School of Medical and Dental Sciences , Tokyo Medical and Dental University , Tokyo , Japan .
authors.forename: Kaori
authors.initials: K
authors.lastname: Watanabe-Imai
authors.affiliation: a Department of Pharmacovigilance and.|b Department of Rheumatology Graduate School of Medical and Dental Sciences , Tokyo Medical and Dental University , Tokyo , Japan .
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Komano
authors.affiliation: a Department of Pharmacovigilance and.|b Department of Rheumatology Graduate School of Medical and Dental Sciences , Tokyo Medical and Dental University , Tokyo , Japan .
authors.forename: Ryoko
authors.initials: R
authors.lastname: Sakai
authors.affiliation: a Department of Pharmacovigilance and.|b Department of Rheumatology Graduate School of Medical and Dental Sciences , Tokyo Medical and Dental University , Tokyo , Japan .
authors.forename: Hayato
authors.initials: H
authors.lastname: Yamazaki
authors.affiliation: d NTT Sapporo Medical Center , Sapporo , Hokkaido , Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Koike
authors.affiliation: b Department of Rheumatology Graduate School of Medical and Dental Sciences , Tokyo Medical and Dental University , Tokyo , Japan .
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyasaka
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001688:Biological Products / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000209:etiology*; D012306:Risk
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products
keywords: Biological disease-modifying antirheumatic drug; Cohort study; Lymphoma; Malignancy; Rheumatoid arthritis