Background/Purpose: The anti-inflammatory and immune-modulating effects of statins suggest that these drugs may influence the risk of developing autoimmune diseases, such as rheumatoid arthritis (RA).  We aimed to perform a systematic review and meta-analysis of studies assessing the risk of RA in statin-users versus non-users.

Methods: We searched Medline from inception to 01/22/2019 and Embase from 1988 to week 03 2019 for all comparative studies that examined the association between statin use and the risk of RA without restrictions on language.  Two reviewers independently selected studies with very good inter-rater agreement (Cohen’s Kappa coefficient 0.90).  Data on study characteristics and adjusted effect estimates were extracted. A random-effects model was used to pool estimates and generate risk ratio (RR) and 95% confidence intervals (CI).

Results: The literature search identified 1,161 references; of which 8 studies (5 cohort and 3 case-control studies) were included in the systematic review.  Six studies comparing statin users vs non-users were included in the meta-analysis and showed no significant difference in the risk of developing RA (RR 1.01; 95%CI 0.88-1.15; I²=65%).  Similar results were shown when cohort studies (RR 1.01; 95%CI 0.93-1.10, I²=17%) or case-control studies (RR 1.01; 95%CI 0.36-2.87, I²=92%) were analyzed separately.  Two studies assessing persistence with or intensity of treatment with statins showed lower risk of RA in persons with higher as opposed to lower treatment persistence or intensity of statin use (pooled RR 0.66; 95%CI 0.5-0.87; I²=83%).

Conclusion: In this systematic review and meta-analysis, observational evidence suggested that statin users had similar risk of RA as non-users.  Considering some imprecision of the effects based on the 95% CIs, potentially with either meaningful benefit or harm of statin exposure on the risk of RA, it appears premature to conclude the lack of effect at this point.  The risk of RA may be lower in patients who have higher as opposed to lower treatment persistence or intensity of statin use, suggesting potential heterogeneity of treatment effect.  More studies at lower risk of bias are needed to further elucidate the impact of statin use on the risk of RA, considering potential differences by dosage, duration of use, study population and other factors.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/what-is-the-effect-of-statins-on-the-risk-of-rheumatoid-arthritis-results-of-a-systematic-review-and-meta-analysis/