Disease-modifying anti-rheumatic drugs and non-melanoma skin cancer in inflammatory arthritis patients: a retrospective cohort study

Rheumatology (Oxford). 2016 Sep;55(9):1594-600. doi: 10.1093/rheumatology/kew214. Epub 2016 May 15.


Objectives: The aim was to determine the non-melanoma skin cancer (NMSC) risk in patients with RA or PsA exposed to MTX and other DMARDs.

Methods: Information on medication was collected on 405 patients with RA or PsA in two private rheumatology practices and was matched to comprehensive histologically confirmed cancer registry data for the years 1978-2005. Relative risks (RRs) were estimated by logarithmic binomial modelling, and standardized incidence ratios (SIRs) were calculated from year-, sex- and age-specific rates of NMSC for the local population.

Results: Compared with no MTX usage, any MTX usage was associated with a higher rate of at least one histopathologically confirmed NMSC (SIR 4.64, 95% CI: 0.67, 33.2). The SIR was 4.81 (95% CI: 3.60, 6.29) for those receiving a cumulative dose >8000 mg compared with SIR 2.31 (95% CI: 1.58, 2.36) for <5000 mg. An increased risk was shown for both basal cell carcinomas and squamous cell carcinomas, with an apparent dose-response relationship for basal cell carcinomas but not for squamous cell carcinomas. There was an increased risk of NMSC in patients taking CSA (RR = 2.51, 95% CI: 1.23, 5.13) and D-Pen (RR 3.49, 95% CI: 1.34, 4.63) in addition to MTX, but not for patients taking AZA or LEF.

Conclusion: MTX, and concurrent MTX and CSA or D-Pen use, is associated with an increased risk of NMSC. These results should encourage greater clinical vigilance for NMSC in treated patients with RA and PsA.

Keywords: d-penicillamine; methotrexate; psoriatic arthritis; rheumatoid arthritis; skin cancer.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / drug therapy*
  • Carcinoma, Basal Cell / chemically induced*
  • Carcinoma, Squamous Cell / chemistry*
  • Female
  • Humans
  • Male
  • Methotrexate / adverse effects*
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Skin Neoplasms / chemically induced*


  • Antirheumatic Agents
  • Methotrexate