Comorbidities in early rheumatoid arthritis

All of the studies that form part of this thesis concern the subject of comorbid conditions in early rheumatoid arthritis (RA). We have used linkage of Swedish clinical and demographic registers as well as the Swedish Rheumatology Quality Register (SRQ) and the Epidemiological Investigation of RA (EIRA) study to investigate the prevalence of comorbidities in early RA, the influence of comorbidities on the choice of antirheumatic treatment and on the chance of remission.

In study I, we compared the prevalence of comorbidities in 11 086 patients with early RA with 54 813 matched controls. We found that respiratory, endocrine and certain neurological diseases were more common among RA patients than controls, whereas psychiatric and malignant comorbidities were less common, particularly in patients with seropositive RA. The difference in comorbidity burden was small, but found to be slightly higher in patients with RA compared to controls, especially in patients with seronegative disease.

In study II, we examined whether comorbidities were associated with the choice of disease-modifying antirheumatic drugs (DMARDs). We compared the DMARDs at diagnosis and after one year in 13 505 patients with early RA in relation to their comorbidity status. Most patients were treated with methotrexate (MTX) monotherapy, although there were differences among the comorbidity categories, with the lowest use in patients with chronic kidney disease (CKD) and respiratory diseases. After one year, 13% were treated with biological/targeted synthetic (b/ts)DMARDs, with the lowest proportion among patients with a history of cancer. It was more common among older patients and those with a higher comorbidity burden not to be treated with any DMARD one year after diagnosis, particularly patients with CKD, respiratory diseases or previous infections.

In study III, we evaluated whether comorbidities affected the likelihood of reaching remission, in 11 001 early RA patients treated with MTX monotherapy. After 3 months, approximately half of the patients failed to reach 28-joint Disease Activity Score (DAS28) remission, with the highest degree among patients with CKD and the lowest degree among patients with a previous cancer. The relative risk of failure to reach remission was increased among patients with endocrine, gastrointestinal, infectious, psychiatric and respiratory diseases. Having a higher overall comorbidity burden was also associated with remission failure. The results were similar at the 6 months follow-up and when assessed with other standard remission measures.

In study IV, we examined whether obesity and/or overweight were independently associated with an increased risk of remission failure in 1285 patients with early RA from the EIRA study, or if it could be explained by underlying comorbidities or lifestyle factors. We found that the obese patients (BMI ≥30 kg/m2) were at increased risk of DAS28 remission failure compared to normal weight patients (BMI 18.5-24.9 kg/m2) after 3 and 6 months. This association remained after adjustments for comorbidities and other potential confounders, suggesting that the risk associated with obesity cannot be explained by comorbid conditions. No significant association was observed for the overweight patients (BMI 25-29.9 kg/m2).

List of scientific papers

I. Tidblad L, Westerlind H, Delcoigne B, Askling J, Saevarsdottir S. Comorbidities at diagnosis of rheumatoid arthritis: a population-based case-control study. Rheumatology (Oxford). 2021 Aug 2;60(8):3760-3769.
https://doi.org/10.1093/rheumatology/keaa856

II. Tidblad L, Westerlind H, Delcoigne B, Askling J, Saevarsdottir S. Comorbidities and treatment patterns in early rheumatoid arthritis: a nationwide Swedish study. RMD Open. 2022 Dec;8(2):e002700.
https://doi.org/10.1136/rmdopen-2022-002700

III. Tidblad L, Westerlind H, Delcoigne B, Askling J, Saevarsdottir S. Comorbidities and chance of remission in patients with early rheumatoid arthritis receiving methotrexate as first-line therapy: a Swedish observational nationwide study. RMD Open. 2023 Dec 20;9(4):e003714.
https://doi.org/10.1136/rmdopen-2023-003714

IV. Tidblad L*, Öberg Sysojev A*, Delcoigne B, Klareskog L, Alfredsson L, Askling J, Westerlind H*, Saevarsdottir S*. Do concurrent comorbidities explain the increased risk of remission failure in obese patients with early rheumatoid arthritis? *These authors contributed equally to the paper. [Manuscript]