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PLoS One. 2018 Feb 23;13(2):e0193297. doi: 10.1371/journal.pone.0193297. eCollection 2018.

Pattern of risks of rheumatoid arthritis among patients using statins: A cohort study with the clinical practice research datalink.

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Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Department of Toxicogenomics, Maastricht University Medical Center, Maastricht, The Netherlands.
Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Faculty of Sciences, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Clinical and Experimental Immunology, Maastricht University, Maastricht, The Netherlands.
Sint Franciscus Gasthuis, Rotterdam, The Netherlands.
Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Clinical Pharmacy & Toxicology, Maastricht University Medical Center, Maastricht, The Netherlands.
Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands.
Department of Non-communicable Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Health eResearch Centre, Farr Institute for Health Informatics Research, University of Manchester, Manchester, United Kingdom.


We examined the association between statin use and the risk of rheumatoid arthritis (RA), with special focus on describing the patterns of risks of RA during statin exposure in a large population-based cohort in the United Kingdom. In the Clinical Practice Research Datalink, patients aged ≥40 years with at least one prescription of statins (1995-2009) were selected, and matched by age (+/-5 years), sex, practice and date of first prescription of statins to non-users. The follow-up period of statin use was divided into periods of current, recent and past exposure, with patients moving between these three exposure categories over time. Time-dependent Cox models were used to derive hazard ratios (HRs) of RA, adjusted for disease history and previous drug use. The study population included 1,023,240 patients, of whom 511,620 were statin users. No associations were found between RA and current (HRadj,1.06;99%CI:0.88-1.27) or past statin users (HRadj,1.18;99%CI:0.88-1.57). However, in patients who currently used statins, hazard rates were increased shortly after the first prescription of statins and then gradually decreased to baseline level. The risk of developing RA was increased in recent statin users, as compared to non-users (HRadj,1.39;99%CI:1.01-1.90). The risk of RA is substantially increased in the first year after the start of statins and then diminishes to baseline level. These findings may suggest that statins might accelerate disease onset in patients susceptible to develop RA, but in other patients, statins are probably safe and well tolerated, even after prolonged use. Alternatively, we cannot rule out that confounding by cardiovascular risk factors and ascertainment bias may have influenced the findings.

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