Disease-modifying antirheumatic drugs and risk of thyroxine-treated autoimmune thyroid disease in patients with rheumatoid arthritis.

BACKGROUND: Autoimmune thyroid disease (AITD) and rheumatoid arthritis (RA) share a genetic background, and the prevalence of AITD in RA patients is increased. Whereas immunomodulatory treatments are used in RA, they are rarely used in AITD. OBJECTIVES: We hypothesized that disease-modifying antirheumatic drugs (DMARDs) as used in RA might lower the risk of incident AITD. METHODS: A nationwide cohort study including 13,731 patients with new-onset RA from the Swedish Rheumatology Quality Register 2006-2018 and 63,201 matched general population comparators linked to national registers to identify AITD. We estimated relative risks (hazard ratios) of AITD after RA diagnosis in RA patients compared to the general population, and in relation to DMARD treatment, using Cox regression. RESULTS: Following RA diagnosis, 321 (2.3%) of the RA patients and 1838 (2.9%) of the population comparators developed AITD, corresponding to an incidence of 3.7 versus 4.6 per 1000 person-years, hazard ratio, 0.81; 95% CI, 0.72-0.91. The decreased risk of incident AITD among RA patients compared to the general population was most pronounced among biologic DMARD (bDMARD) treated patients, with a hazard ratio of 0.54; 95% CI, 0.39-0.76. Among RA patients, subgrouped by bDMARD use, TNF-inhibitors were associated with the most pronounced decrease, hazard ratio, 0.67; 95% CI, 0.47-0.96. CONCLUSIONS: In contrast to the increased prevalence of AITD in RA patients at diagnosis, our results indicate that the risk of AITD decreases following RA diagnosis. This decrease is especially pronounced in RA patients treated with bDMARDs. These findings support the hypothesis that DMARDs might have a preventive effect on AITD.

Does autoimmune thyroid disease affect rheumatoid arthritis disease activity or response to methotrexate?

OBJECTIVE: To investigate if autoimmune thyroid disease (AITD) impacts rheumatoid arthritis (RA) disease activity or response to methotrexate. METHODS: A nationwide register-based cohort study of 9 004 patients with new-onset RA from the Swedish Rheumatology Quality Register year 2006-2016, with linkage to other nationwide registers to identify comorbidity with AITD defined as thyroxine prescription before RA diagnosis, excluding non-autoimmune causes. We compared RA disease activity using 28-joint Disease Activity Score (DAS28) and its components, and EULAR response, between patients with and without AITD, using logistic regression. RESULTS: At diagnosis, patient reported outcome measures (PROMs; patient global, Health Assessment Questionnaire Disability Index and pain) but not objective disease activity measures (erythrocyte sedimentation rate and swollen joint count) were significantly higher (p<0.05 for all PROMs) among RA patients with AITD compared with those without. The level of DAS28 was 5.2 vs 5.1. By contrast, AITD had little influence on EULAR response to methotrexate at 3 months (OR of non/moderate response=0.95, 95% CI 0.8 to 1.1), nor at 6 months. When stratified by age, however, AITD was more common among EULAR non/moderate responders at 3 and 6 months in patients below 45 years resulting in ORs of non/moderate response of 1.44 (0.76-2.76) and 2.75 (1.04-7.28). CONCLUSION: At diagnosis, RA patients with concomitant AITD score worse on patient reported but not on objective RA disease activity measures, while DAS28 was only marginally elevated. The overall chance of achieving a EULAR good response at 3 or 6 months remains unaffected, although among a limited subgroup of younger patients, AITD may be a predictor for an inferior primary response.

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

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.

Validation of the rheumatoid arthritis diagnosis in the Swedish National Patient Register: a cohort study from Stockholm County.

BACKGROUND: The Swedish National Patient Register offers unique possibilities for identification of large cohorts, such as patients with rheumatoid arthritis (RA). Although the overall diagnostic validity in the register has been reported as good, the aims of this study were to a) specifically validate the RA diagnosis from contemporary outpatient specialist care in this register, and b) assess the proportion of patients identified via algorithms to define incident RA in the register who in clinical practice also have new-onset disease. METHODS: 211 individuals with prevalent or incident RA in the National Patient Register were included. By extracting diagnosis-related parameters from their medical records, we determined if the patient fulfilled the 2010 ACR/EULAR- and the 1987 ACR-classification criteria for RA. We also determined whether clinical diagnosis was synchronous with disease onset as defined through register-based algorithms. RESULTS: For 91% of the prevalent patients, the RA diagnosis in the National Patient Register fulfilled classification criteria or clinical diagnosis for RA. Among individuals identified with incident RA using a strict algorithm for new-onset disease, the RA diagnosis was substantiated in 91%, of whom 92% also represented new-onset disease. CONCLUSIONS: The validity of the RA diagnosis in the National Patient Register was high and, by using specific algorithms, new-onset RA can be defined. These findings strengthen the notion that the National Patient Register may be used to define RA populations with high validity to allow for high-quality epidemiological studies.