The impact of autoimmune thyroid disease (AITD) on rheumatoid arthritis (RA) and the impact of RA on AITD

Abstract: Study I. Background: The Swedish National Patient Register (NPR) is a unique source for the identification of large cohorts of rheumatoid arthritis (RA) patients. The general validity of this register has been reported to be high. Aims: The aims were to specifically validate the RA diagnosis from the outpatient specialist care in this register, and to assess the proportion of patients identified through specific algorithms to define incident RA, who in clinical practice would be assessed as new-onset disease. Methods: Diagnosis-related parameters were extracted from the medical records of approximately 200 patients coded with a RA diagnosis in the NPR, of whom the majority was also included in the Swedish Rheumatology Quality Register (SRQ). The patients were assessed if they fulfilled the 1987 ACR- and 2010 ACR/EULAR classification criteria for RA. Furthermore, it was determined if clinical diagnosis correlated with disease onset as defined through register-based algorithms. Results: The prevalent and strictly incident patients with a RA diagnosis fulfilled to a large extent (>90%) the classification criteria or clinical diagnosis for RA and the patients coded as incident RA represented new-onset disease. Conclusion: The validity of the RA diagnosis was high and specific algorithms adequately identified new-onset RA, which allows the NPR to be used to identify RA populations with high validity for epidemiological studies. Study II. Background: Autoimmune thyroid disease (AITD), including hypothyroidism and hyperthyroidism, is the most common organ-specific autoimmune disorder in the general population. AITD and RA share genetic background and the prevalence of AITD is also increased in patients with RA. Studies on when the increased risk of AITD develops in relation to time before and after RA diagnosis are missing. Aims: The aim was to assess the risk of thyroxine treated AITD at different points in time before and after RA diagnosis. Methods: By using the SRQ and other nationwide registers approximately 8000 early RA patients and 80 000 controls were identified. A combined case-control and cohort design was used to investigate the prevalence and relative risk of incident AITD up to 7 years before and 8 years after RA diagnosis. AITD was defined as thyroxine prescription in the Swedish Prescribed Drug Register (PDR), with exclusion of non-autoimmune indications. Results: The prevalence of AITD was approximately 10% at time of RA diagnosis. The risk of new-onset AITD increased during a 5-year period prior to RA diagnosis. By contrast, following the diagnosis of RA, the risk of developing AITD decreased below the expected rate. Conclusion: The temporal pattern of AITD risk in relation to RA diagnosis raised the questions of a potential temporal change in diagnostic intensity, a bilateral influence between the two conditions or a potential protective effect of antirheumatic therapies. Study III. Background: Although AITD is one of the most common comorbidities in RA it is less well understood if AITD might affect RA disease activity or response to anti-rheumatic therapies. Aims: The aims were to compare disease activity and treatment response to the first-line therapy with methotrexate in early RA patients with AITD versus those without this comorbidity. Methods: The SRQ and other nationwide registers were used to identify approximately 9000 RA patients and comorbidity with AITD to compare the disease activity at the 3- and 6- month follow-up visits, based on DAS 28 and its individual components, and EULAR response criteria. Results: AITD was associated with worse subjective- but not objective measures of disease activity among RA patients. AITD did not impact the overall treatment response, but a subgroup of younger patients with both RA and AITD were less likely to achieve a good treatment response to methotrexate. Conclusions: Concomitant AITD impacts the RA disease activity measures used in clinical practice through worse subjective disease activity components and thus the composite disease activity measures. It is of importance to analyze all individual disease activity components when treating and evaluating patients with early RA and concomitant AITD. Study IV. Background/Aims: Based on the result from study II, we investigated if biologic diseasemodifying antirheumatic drugs (bDMARDs) used for the treatment of RA might lower the risk of developing AITD. Methods: The SRQ and other nationwide registers were used to perform a cohort study including approximately 13 000 RA patients and 63 000 population controls to estimate the relative risk of AITD following RA diagnosis, compared to the general population controls, and in relation to treatment with bDMARDs. Results: The risk of developing AITD following RA diagnosis was decreased in RA patients compared to controls and this was most pronounced in RA patients treated with bDMARDs. Conclusion: Treatment with bDMARDs may have and preventive effect on AITD.