Atorvastatin did not prevent the development of arthritis in individuals at high risk for rheumatoid arthritis (RA), according to study findings published in RMD Open. However, the clinical trial was terminated early due to low enrollment.
Studies have reported disease-modifying effects of statins on RA and, at the population level, decreased development of RA with statin use. This study was undertaken to investigate the use of statin therapy for RA prevention.
Criteria for enrollment in this randomized, double-blind, placebo controlled trial (STAtins to Prevent Rheumatoid Arthritis [STAPRA] trial: TrialRegister.nl Identifier: NTR5265) included patients age 18 or older, an absence of clinical arthritis symptoms, and a high risk for developing RA. High risk was defined as either having anticitrullinated protein antibodies (ACPA) greater than 3 times the upper limit of normal (≥21 kU/L) or having both ACPA of7 kU/L or greater and rheumatoid factor ≥5 kU/L. Patients were randomly assigned to receive 40 mg of atorvastatin daily or placebo for 3 years. The primary outcome was the development of clinical arthritis, defined as at least one swollen joint.
Although the calculated cohort size was 220 patients, only 62 participants were enrolled (31 in the atorvastatin group and 31 in the placebo group). In total, 15 of the participants developed arthritis: 29% in the atorvastatin group and19% in the placebo group. The difference was not significant (HR 1.40; 95% CI, 0.50 to 3.95).
The main limitation of the study was the inability to achieve the required sample size. The researchers reported that 62% of eligible individuals declined to participate due to aversion to the trial medication (58%) or a perceived burden of participation (23%). In addition, there was a high drop-out rate (27%), largely due to adverse events which were similar in both groups.
The researchers noted, “This inconclusive trial of a low impact intervention to prevent RA highlights recruitment and retention issues. Such issues must be resolved for RA prevention to move forward.”
van Boheemen L, Turk S, van Beers-Tas M, et al. Atorvastatin is unlikely to prevent rheumatoid arthritis in high risk individuals: results from the prematurely stopped STAtins to Prevent Rheumatoid Arthritis (STAPRA) trial. RMD Open. Published online March 7, 2021. doi:10.1136/rmdopen-2021-001591