Abstract
ObjectiveTo evaluate the association between statin use and the risk of developing rheumatoid arthritis (RA) in a large, US case-control study.MethodsUsing the OptumLabs Data Warehouse, RA cases were identified as patients aged ≥18 years with ≥2 RA diagnoses between January 1, 2010 and June 30, 2019 and ≥1 prescription fills for methotrexate within 1 year of the first RA diagnosis. The first RA diagnosis was the index date. Cases were matched 1:1 to controls on age, sex, region, year of index date, and length of baseline coverage. Statin users were defined by having ≥2 statin prescription fills at least 90 days pre-index. Patients identified as statin users were further classified by statin user status (current or former), statin use duration, and intensity of statin exposure. Odds ratios for RA risk with statin use were estimated using logistic regression.Results16,363 RA cases and 16,363 matched controls were identified. Among RA cases, 5509 (33.7%) patients were statin users compared to 5164 (31.6%) of the controls. Statin users had a slightly increased risk of RA compared to non-users (OR 1.12, 95% CI 1.06–1.18), and former statin users had an increased RA risk compared to current users (OR 1.21, 95% CI 1.13–1.28). However, risk was eliminated following adjustment for hyperlipidemia. The risk estimates for statin use duration and intensity did not reach significance.ConclusionThis study demonstrates no significant increase in the risk of developing RA for statin users compared to non-users after adjustment for hyperlipidemia in addition to other relevant confounders. However, more information from prospective studies would be necessary to further understand this relationship.
Highlights
Statins, or 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, are among the most widely prescribed drugs in the US [1] and are proven to reduce the risk of cardiovascular morbidity and mortality by inhibiting cholesterol synthesis [2,3,4,5,6]
Case definition and selection Cases were defined as individuals aged ≥18 years who had two or more claims containing an rheumatoid arthritis (RA) diagnostic code [International Classification of Disease (ICD)-9: 714.0, 714.1, 714.2; ICD-10: M05.xxx, M06.0xx, M06.8x, M06.9] between January 1, 2010 and June 30, 2019 with diagnoses being at least 30 days but no more than 365 days apart and one or more prescription fills for methotrexate (MTX) within 30 days before and 365 days after the first RA diagnosis
The highest statin dosage ever filled for most statin users was a medium intensity statin
Summary
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, are among the most widely prescribed drugs in the US [1] and are proven to reduce the risk of cardiovascular morbidity and mortality by inhibiting cholesterol synthesis [2,3,4,5,6]. The anti-inflammatory and immunomodulatory effects of statins have been observed in randomized controlled trials and observational studies in the general population [9] and in patients with chronic inflammatory diseases, such as rheumatoid arthritis (RA) [10,11,12,13]. In RA patients, statins have been shown to reduce C-reactive protein levels, joint inflammation, and overall disease activity [12, 14,15,16]. Literature regarding the role of statins in the development of RA is conflicting with studies reporting a harmful [18, 19], protective [20,21,22], or neutral effect [23,24,25] on incident RA. Large studies examining the association between statin use and RA risk in the US are lacking
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