Background/Purpose: Human papillomaviruses (HPV) are causes of high-grade cervical dysplasia and cervical cancer. Persistent HPV infection, the major risk factor for cervical cancer, is associated with several factors including HPV genotypes, multiple sexual partners, history of sexually transmitted disease (STD), and immunosuppression. A recent large cohort study found a higher risk of high-grade cervical dysplasia and cervical cancer in patients with rheumatoid arthritis (RA) compared to non-RA patients. The objective of this study was to assess the risk of high-grade cervical dysplasia or cervical cancer related to use of biologic disease-modifying antirheumatic drug (DMARD) versus only non-biologic DMARDs for RA.    

Methods: Using U.S. commercial insurance claims data (2001-12), we conducted a cohort study to examine the incidence rates (IR) of high-grade cervical dysplasia or cervical cancer in women who initiated biologic or non-biologic DMARDs for RA. The index date was defined as the date of the first biologic or non-biologic DMARD after ≥2 diagnoses of RA. Patients were required to have an enrollment period of ≥365 days prior to the index date for baseline covariate assessment. High-grade cervical dysplasia or cervical cancer was defined by a validated claims-based algorithm with a positive predictive value of ≥81%. The number of gynecologic (Gyn) visits or procedures during follow-up was also assessed. To control for potential confounders such as age, being sexually active, comorbidities including STD, medications, prior Papanicolaou test, and healthcare utilization, biologic DMARD initiators were matched to non-biologic DMARD initiators on the propensity score (PS) with a 1:1 ratio.

Results: 7,539 PS-matched pairs of biologic and non-biologic DMARD initiators were included with a mean age of 50 years. 39% had a Papanicolaou test at baseline. During a mean (SD) duration of active treatment of 1.4 (1.5) years, 20 developed high-grade cervical dysplasia or cervical cancer. The IR of high-grade cervical dysplasia or cervical cancer per 1,000 person-years was 1.12 in biologic DMARD initiators and 0.70 in non-biologic DMARD initiators. The hazard ratio was 1.63 (95%CI 0.62-4.27) for biologic DMARD compared to non-biologics (Table). The number of outpatient Gyn visits (Rate ratio [RR] 0.96, 95%CI 0.88-1.04) and Gyn procedures (RR 0.94, 95%CI 0.86-1.02) was not different between the groups.

Conclusion: Among women with RA, initiation of biologic DMARDs may be associated with a moderately increased, albeit not statistically significant, risk of high-grade cervical dysplasia or cervical cancer, although the absolute risk was low. Both biologic and non-biologic DMARD initiators had a similar number of Gyn visits and procedures during follow-up. Future research should determine the need for more intensive cervical cancer screening strategy in RA patients.