Arthritis Prevention in the Pre-Clinical Phase of RA with Abatacept (the APIPPRA Study): A Multi-Centre, Randomised, Double Blind, Parallel Group Placebo-Controlled Clinical Trial

Background: Individuals with joint pain and carrying serum autoantibodies associated with rheumatoid arthritis (RA) are at high risk of developing RA. While there are currently no evidence-based guidelines to inform therapy decisions for such subjects, there are therapies licensed for the treatment of established RA that target pathways implicated in the earliest phase of the disease. Accordingly, we set out to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first in class costimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis. Methods and Design The APIPPRA study was designed as a randomised, double blind, parallel group placebo-controlled clinical trial, aiming to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlands. Participants aged 18 or over who report inflammatory sounding joint pain (clinically suspicious arthralgia) and who are found to be positive for serum autoantibodies associated with RA, will be randomised to receive weekly injections of investigational medicinal product (IMP), either abatacept or placebo treatment over a 52-week period. All study subjects consent to a further 52 weeks of follow up to monitor for the primary endpoint, the time to development of ≥ 3 swollen joints, or to the fulfillment of the 2010 ACR/EULAR classification criteria for RA using swollen but not tender joints, whichever endpoint is met first. In either case, swollen joints are confirmed by ultrasonography. Discussion There is limited experience of the design and implementation of trials for the prevention of inflammatory joint diseases. Here, we propose to explore the effects of immunomodulatory therapy at the very earliest detectable phase of disease using an intervention that is already licensed for use in established RA. We discuss the rationale behind choice and duration of treatment, the challenges associated with defining the “at risk” state, and offer pragmatic solutions in the protocol to enrolling subjects at risk of RA. Trial registration Current Controlled Trials, ID: ISRCTN46017566. Registered on 04 July 2014