Objectives To study whether oral contraceptive (OC) use or breastfeeding (BF) influence the risk of rheumatoid arthritis (RA), stratifying the cases by presence/absence of anticitrullinated protein antibodies (ACPA), and whether these factors interact with known risk factors in the development of ACPA-positive RA.
Methods Women aged ≥18 years, participants in the population-based case–control Swedish Epidemiological Investigation of RA study (2641 cases/4251 controls), completed an extensive questionnaire regarding OC, BF and potential confounders. We calculated ORs, with 95% CIs, adjusted for age, residential area, smoking and alcohol consumption. Attributable proportion due to interaction (AP) was estimated to evaluate presence of interaction.
Results Compared with never users, ever and past OC users had a decreased risk of ACPA-positive RA (OR=0.84 (95% CI 0.74 to 0.96); OR=0.83 (95% CI 0.73 to 0.95), respectively). No significant associations were found for ACPA-negative RA. Long duration of OC use (>7 years vs never use) decreased the risk of both ACPA-positive (p=0.0037) and ACPA-negative RA (p=0.0356).
A history of long BF decreased the risk only of ACPA-positive RA in a dose-dependent manner (p=0.0086), but this trend did not remain after adjustments. A significant interaction was observed between the lack of OC use and smoking (AP=0.28 (95% CI 0.14–0.42)) on the risk of ACPA-positive RA. No interactions were found for BF.
Conclusions OC decreased the risk of RA, especially ACPA-positive RA, where an interaction with smoking was observed. A long duration of OC use decreased the risk of both disease subsets. We could not confirm an association between BF and a decreased risk of either ACPA-positive or ACPA-negative RA.
- rheumatoid arthritis
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Contributors CO conducted the statistical analyses and drafted the manuscript; CB initiated the study and was responsible for the analysis, interpreting the results and revising the manuscript; LA, LK and CB contributed to study design; and LA, LK, EWK and SS contributed to data interpretation and critical revision of the manuscript for important intellectual content. All authors have read and approved the final manuscript.
Funding This study was supported by grants from the Swedish Medical Research Council, the Swedish Research Council for Health, Working Life and Welfare, King Gustav Vâ€™s 801-year foundation, Vinnova, the Swedish Foundation for Strategic Research, the Swedish Rheumatic Foundation, the Stockholm County Council, the Insurance Company AFA, the Innovative Medicines Initiative 1 supported BTCure project and the National Institutes of Health (NIH, AR047782). The funding sources had no role in the reporting of the study or in the decision to submit the manuscript for publication.
Competing interests No, there are no competing interests.
Patient consent Obtained.
Ethics approval This study was approved by the Regional Ethical Review Board at Karolinska Institutet, Stockholm, Sweden.
Provenance and peer review Not commissioned; externally peer reviewed.
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