Persons at high risk of rheumatoid arthritis (RA) might benefit from a low-risk pharmacological intervention aimed at primary prevention. Previous studies demonstrated disease-modifying effects of statins in patients with RA as well as an association between statin use and a decreased risk of RA development. A randomised, double-blind, placebo-controlled trial investigated whether atorvastatin could prevent arthritis development in high-risk individuals.
Arthralgia patients with anticitrullinated protein antibody (ACPA) >3 xULN or ACPA and rheumatoid factor, without (a history of) arthritis, were randomised to receive atorvastatin 40 mg daily or placebo for 3 years. The calculated sample size was 220 participants. The primary endpoint was clinical arthritis. Cox regression analysis was used to determine the effect of atorvastatin on arthritis development.
Due to a low inclusion rate, mainly because of an unwillingness to participate, the trial was prematurely stopped. Data of the 62 randomised individuals were analysed. Median follow-up was 14 (inner quartiles 6-35) months. Fifteen individuals (24%) developed arthritis: 9/31 (29%) in the atorvastatin group; 6/31 (19%) in the placebo group: HR 1.40, 95% CI 0.50 to 3.95.
In this small set of randomised high-risk individuals, we did not demonstrate a protective effect of atorvastatin on arthritis development. The main reason for the low inclusion was unwillingness to participate; this may also impede other RA prevention trials. Further research to investigate and solve barriers for prevention trial participation is needed.