Risk of Thyroxine-Treated Autoimmune Thyroid Disease Associated With Disease Onset in Patients With Rheumatoid Arthritis

Abstract

Importance: Autoimmune thyroid disease ([AITD] including hypothyroidism and hyperthyroidism) is the most common organ-specific autoimmune disorder and is more prevalent among patients with rheumatoid arthritis (RA). Real-world studies on when and how this increased risk of AITD develops, in association with the time before or after the onset of RA, are lacking. Objective: To estimate the risk of thyroxine-treated AITD among patients with RA at different time points before and after the diagnosis of RA. Design, Setting, and Participants: A nationwide register-based case-control and cohort study was conducted between January 1, 2006, and June 30, 2013, with a maximum follow-up time of 7 years before and 8 years after diagnosis of RA. The study used the Swedish Rheumatology Quality Register and linkage to other nationwide registers to identify 8090 adults with new-onset RA and a random population-based sample of 80 782 referents matched by age, sex, and residential area. Statistical analysis was performed from July 1, 2015, to June 30, 2017. Exposures: Presence of AITD in the participants in the case-control design and RA in the participants in the cohort design. Main Outcomes and Measures: Prevalence and relative risk of incident AITD before (odds ratios) and after (hazard ratios) diagnosis of RA compared with the population as reference. Results: There were 8090 patients with RA (5529 women and 2561 men; mean [SD] age, 58.3 [15.2] years) and 80 782 population-based participants as reference who were identified. By the time of diagnosis of RA, the prevalence of AITD was 10.3% among the patients with RA (n = 832) vs 7.1% among the controls (5725 of 80 350) (odds ratio, 1.5; 95% CI, 1.4-1.7). This increased risk of AITD developed during the 5 years (range, 2-5 years) before diagnosis of RA (odds ratio, 1.5; 95% CI, 1.2-1.8) and peaked by the time of diagnosis of RA (range, 0-3 months before diagnosis of RA) (odds ratio, 5.3; 95% CI, 3.7-7.6). From diagnosis of RA and onward, the risk of developing AITD decreased (range, 2-5 years after diagnosis of RA) (hazard ratio, 0.7; 95% CI, 0.5-1.0). Conclusions and Relevance: Compared with the general population, Swedish patients with RA appear to have a higher prevalence of thyroxine-treated AITD at diagnosis of RA and an increased incidence of AITD during the 5-year period before diagnosis of RA. After diagnosis of RA, the risk of developing AITD is suggested to decrease below the expected rate. Besides temporal changes in diagnostic intensity, this pattern of risk raises the question whether AITD may influence the pathogenesis of RA (or vice versa) and, conversely, the question whether antirheumatic therapies may prevent AITD.