AB0286 STATINS TO PREVENT RHEUMATOID ARTHRITIS (STAPRA TRIAL): CHALLENGES IN RECRUITMENT AND RETENTION

Abstract

Background: Primary prevention may be possible in subjects at high risk to develop rheumatoid arthritis (RA). We designed a placebo controlled randomized trial to investigate if atorvastatin can halt RA development in persons at risk for this disease (STAPRA, Netherlands Trial Register NTR5265). A statin was chosen because these drugs reduce disease activity in RA (1), hyperlipidemia patients on statins have a lower risk for developing RA (2) and dyslipidemia increased the risk for RA in a seropositive arthralgia cohort (3). We assumed that high risk-subjects would be attracted to this trial. However, we experienced severe difficulties with patient inclusion and treatment adherence. Objectives: To explore difficulties with patient recruitment and retention. Methods: The STAPRA study is a multicenter, 3-year, randomized, placebo controlled, double-blind clinical trial to assess the efficacy of atorvastatin 40 mg daily in delaying or preventing RA development in persons at high risk, defined by the presence of arthralgia and the presence of high titers of anti-citrullinated protein antibody (ACPA) or presence of both ACPA and rheumatoid factor (RF). Eligible participants were ≥18 years, did not use lipid lowering agents and had no synovitis. Five centers participated. Our goal was to recruit 220 study subjects based on an expected risk reduction of 21%. The unexpected low recruitment rate prompted us to evaluate the reasons to decline participation or to discontinue the study drug prematurely. Results: Details were available from the initiating center (Reade) and 1 participating center (Sint Maartenskliniek (SMK)). During a period of 36 months, 164 eligible patients were asked to participate of whom 58 patients (35%) consented. Most common reasons to decline were: unwillingness to use study medication (49%) and the feeling that participation was too time-consuming (14%). Fifty-four patients were randomized since 4 failed screening due to hyperlipidemia or seronegativity on repeated testing. Currently, 11 participants (20%) have developed arthritis. Twelve dropped out for various reasons, including adverse events (33%). Thirtyone persons are still being followed, but of these 10 stopped study medication after a median of 3 months. The main reason to discontinue therapy was side effects (80%), notwithstanding a standardized approach for dose reduction and temporary discontinuation as needed. Conclusion: In this RCT in persons at risk for RA we identified a major obstacle to the successful conduction of such trials, namely the difficulty to enter and retain participants. The primary reported reason was unwillingness to use study medication. This is different from many successfully completed trials on optimal medical treatment in early RA patients, where large inclusion goals have been met within a relatively short timeframe and adherence overall was good. This issue is highly relevant to the current inclination to move the start of drug intervention in RA to ever earlier phases. Further research into patients' motivation and barriers for participation in intervention trials in the at risk phase of RA is necessary to enable intervention research in this phase of the disease. (Figure presented).