Biologic Disease-Modifying Antirheumatic Drugs and Risk of High-Grade Cervical Dysplasia and Cervical Cancer in Rheumatoid Arthritis: A Cohort Study

Arthritis Rheumatol. 2016 Sep;68(9):2106-13. doi: 10.1002/art.39689.


Objective: Recent research showed an increased risk of high-grade cervical dysplasia and cervical cancer associated with rheumatoid arthritis (RA). The purpose of this study was to examine whether this risk was associated with the use of biologic versus nonbiologic disease-modifying antirheumatic drugs (DMARDs).

Methods: We identified RA patients in the US Medicaid and commercial insurance databases (for the years 2000-2012) who were starting treatment with either a biologic or a nonbiologic DMARD. High-grade cervical dysplasia or cervical cancer was identified with a validated claims-based algorithm, and we assessed utilization of gynecologic procedures. To control for potential confounders, those starting therapy with a biologic DMARD were matched 1:1 to those starting therapy with a nonbiologic DMARD according to the propensity score (PS). Hazard ratios (HRs) and rate ratios (RRs) in the PS-matched Medicaid and commercial insurance cohorts were pooled by an inverse variance-weighted fixed-effects model.

Results: We included 14,729 pairs of patients initiating biologic and nonbiologic DMARDs from the Medicaid cohort and 7,538 pairs from the commercial insurance cohort. During 73,389 person-years of active treatment with either biologic or nonbiologic DMARDs, 95 cases of high-grade cervical dysplasia or cervical cancer occurred in the 2 cohorts. The HR for high-grade cervical dysplasia or cervical cancer associated with biologic DMARD use was 1.25 (95% confidence interval [95% CI] 0.78-2.01) in the Medicaid cohort and 1.63 (95% CI 0.62-4.27) in the commercial insurance cohort, with a pooled HR of 1.32 (95% CI 0.86-2.01). The rate of gynecologic procedures involving the uterine cervix was not different between the 2 groups (pooled RR 0.96 [95% CI 0.90-1.02]).

Conclusion: Among women with RA, initiation of therapy with a biologic DMARD was associated with a numerically significant, but not statistically significant, increase in the risk of high-grade cervical dysplasia or cervical cancer as compared to initiation of a nonbiologic DMARD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / drug therapy*
  • Cohort Studies
  • Female
  • Humans
  • Middle Aged
  • Risk Assessment
  • Uterine Cervical Dysplasia / chemically induced*
  • Uterine Cervical Dysplasia / epidemiology*
  • Uterine Cervical Neoplasms / chemically induced*
  • Uterine Cervical Neoplasms / epidemiology*


  • Antirheumatic Agents