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

Mod Rheumatol. 2016 Sep;26(5):642-50. doi: 10.3109/14397595.2016.1141740. Epub 2016 Mar 11.


Objectives: 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.

Keywords: Biological disease-modifying antirheumatic drug; Cohort study; Lymphoma; Malignancy; Rheumatoid arthritis.

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Biological Products / adverse effects*
  • Biological Products / therapeutic use
  • Cohort Studies
  • Female
  • Humans
  • Incidence
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Neoplasms / epidemiology*
  • Neoplasms / etiology*
  • Risk


  • Antirheumatic Agents
  • Biological Products