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 Protocol

Abstract

Trial design: We present a study protocol for a multi-centre, randomised, double blind, parallel group, placebo-controlled trial that seeks 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: The study aimed 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 were eligible for enrolment. All study subjects were randomised to receive weekly injections of investigational medicinal product (IMP), either abatacept or placebo treatment over a 52-week period. Participants were then followed up for a further 52 weeks. The primary endpoint was defined as the time to development of ≥ 3 swollen joints, or to the fulfilment of the 2010 ACR/EULAR classification criteria for RA using swollen but not tender joints, whichever endpoint was met first. In either case, swollen joints were confirmed by ultrasonography. Participants, care givers, and those assessing the outcomes were all blinded to group assignment. Clinical assessors and ultrasonographers were also blinded to each other’s assessments for the duration of the study. Conclusions: There is limited experience of the design and implementation of trials for the prevention of inflammatory joint diseases. 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.

Patients’ and rheumatologists’ perceptions on preventive intervention in rheumatoid arthritis and axial spondyloarthritis

“…Environmental factors including lifestyle are important in RA development and lifestyle intervention may delay or prevent RA onset [5][6][7]. In addition, several placebo controlled clinical trials in individuals at increased risk of RA have been performed or are ongoing [8][9][10].…”

High serum IgA and proportion of activated Th17 and Treg predict efficacy of abatacept in patients with early, seropositive rheumatoid arthritis

“…In fact, a trial suggested the possibility that abatacept may alter the progression of RA at a very early stage, although it was not found to be statistically signi cant [38]. To con rm this, a larger randomized trial is in process [39].…”

The Role of Musculoskeletal Ultrasound in the Rheumatoid Arthritis Continuum

“…Such patients, in the earliest phases of clinical disease, are often difficult to assess and the clinical findings can be subtle. Clinical trials investigating arthritis prevention in individuals at-risk of RA are increasingly stipulating US confirmation of clinical synovitis for this reason [18]. Despite the several advantages described above, there are some important considerations which must be borne in mind for the optimum use of US in individuals at-risk of RA without clinical synovitis.…”