The influence of disease-modifying anti-rheumatic drugs and corticosteroids on the association between rheumatoid arthritis and skin cancer: a nationwide retrospective case-control study in Taiwan

Clin Exp Rheumatol. 2018 May-Jun;36(3):471-478. Epub 2017 Dec 15.

Abstract

Objectives: To investigate the influence of corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs, including conventional synthetic and biologic DMARDs) treatment on the association between rheumatoid arthritis (RA) and non-melanoma skin cancer (NMSC).

Methods: This nationwide retrospective case-control study retrieved data from Taiwan National Health Insurance Research Database during 1995-2013. Cases with newly-diagnosed NMSC (n=19,603) were matched with control without NMSC in a 1:1 ratio according to age, sex, and reference date. The aforementioned association was analysed using conditional logistic regression and adjustments for age, sex, residential regions, occupations, and co-morbidities. Causality cannot be inferred by case-control study.

Results: Compared to patients without RA, the patients with RA had a significantly higher association with NMSC (adjusted odds ratio (AOR)=2.23, 95% confidence interval (CI) 1.6-3.1, p<0.001), especially those using cyclosporine (AOR=5.7, 95%CI 2.2-14.86; ≥65 years: AOR=7.28, 95%CI 2.16-24.56), etanercept (AOR=5.27, 95%CI 1.15-24.27; ≥65 years: AOR=8.95, 95%CI 1.12-71.85), and d-penicillamine (AOR=4.79, 95%CI 1.63-14.12; ≥65 years: AOR=3.81, 95%CI 1.26-11.52); those using higher cumulative doses of corticosteroids and methotrexate (corticosteroids: >10g: AOR=2.96, 95%CI 1.67-5.22; >10g and ≥65years: AOR=3.5, 95%CI 1.77-6.92; methotrexate: 1-3g: AOR=2.57, 95%CI 1.13-5.82; >3g: AOR=4.64, 95%CI 1.74-12.4; >3g and ≥65 years: AOR=10.17, 95%CI 2.34-44.26); and those using more kinds of DMARDs (any 3: AOR=3.72, 95%CI 1.67-8.26; any 5: AOR=2.81, 95%CI 1.13-7.04; any 6: AOR=5.23, 95%CI 1.14-24.14; 7-8: AOR=4.06, 95%CI 1.14-14.49).

Conclusions: The patients with RA had significantly increased associations with NMSC, especially those receiving cyclosporine, etanercept, and d-penicillamine; higher cumulative doses of corticosteroids and methotrexate; or more kinds of DMARDs in combination or in sequence. The aforementioned associations were much stronger in the elderly.

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use*
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / epidemiology
  • Carcinoma, Basal Cell / epidemiology*
  • Carcinoma, Squamous Cell / epidemiology*
  • Case-Control Studies
  • Cyclosporine / therapeutic use
  • Databases, Factual
  • Dose-Response Relationship, Drug
  • Etanercept / therapeutic use
  • Female
  • Humans
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Odds Ratio
  • Penicillamine / therapeutic use
  • Retrospective Studies
  • Risk Factors
  • Skin Neoplasms / epidemiology*
  • Taiwan / epidemiology

Substances

  • Adrenal Cortex Hormones
  • Antirheumatic Agents
  • Cyclosporine
  • Penicillamine
  • Etanercept
  • Methotrexate