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

• Published in: Current controlled trials in cardiovascular medicine 2019-07, Vol.20 (1), p.429-15, Article 429
• Main Authors: Al-Laith, Mariam, Jasenecova, Marianna, Abraham, Sonya, Bosworth, Aisla, Bruce, Ian N, Buckley, Christopher D, Ciurtin, Coziana, D'Agostino, Maria-Antonietta, Emery, Paul, Gaston, Hill, Isaacs, John D, Filer, Andrew, Fisher, Benjamin A, Huizinga, Thomas W J, Ho, Pauline, Jacklin, Clare, Lempp, Heidi, McInnes, Iain B, Pratt, Arthur G, Östor, Andrew, Raza, Karim, Taylor, Peter C, van Schaardenburg, Dirkjan, Shivapatham, Dharshene, Wright, Alison J, Vasconcelos, Joana C, Kelly, Joanna, Murphy, Caroline, Prevost, A Toby, Cope, Andrew P
• Format: Article
• Language: English
• Subjects: Abatacept; Abatacept - administration & dosage; Abatacept - adverse effects; Analysis; Antibodies; Antigens; Antirheumatic Agents - administration & dosage; Antirheumatic Agents - adverse effects; Arthralgia; Arthritis; Arthritis, Rheumatoid - diagnosis; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - prevention & control; At risk; Autoantibodies; Autoantibodies - blood; Autoimmunity; Biomarkers - blood; Caregivers; Clinical trials; Diagnostic imaging; Disease prevention; Double-blind; Double-Blind Method; Double-blind studies; Drug Administration Schedule; Drug therapy; Ecology, environment; Family physicians; Feasibility Studies; Female; Health; Humans; Immunotherapy; Intervention; Laboratories; Life Sciences; Male; Medical referrals; Multicenter Studies as Topic; Netherlands; Pain; Patients; Pre-clinical phase; Pregnancy; Prevention; Quality of life; Randomized Controlled Trials as Topic; Remission (Medicine); Rheumatoid arthritis; Rheumatoid factor; Rheumatology; Risk factors; Study Protocol; Time Factors; Treatment Outcome; Tumor necrosis factor-TNF; Ultrasound imaging; United Kingdom
• ISSN: 1745-6215; 1745-6215
• DOI: 10.1186/s13063-019-3403-7

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 co-stimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis. The study aimed to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlands. Participants who were at least 18 years old, who reported inflammatory sounding joint pain (clinically suspicious arthralgia) and who were found to be positive for serum autoantibodies associated with rheumatoid arthritis (RA) were eligible for enrolment. All study subjects were randomly assigned to receive weekly injections of investigational medicinal product, either abatacept or placebo treatment over the course of a 52-week period. Participants were followed up for a further 52 weeks. The primary endpoint was defined as the time to development of at least three swollen joints or to the fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism (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. 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 and the challenges associated with defining the "at risk" state and offer pragmatic solutions in the protocol to enrolling subjects at risk of RA. Current Controlled Trials, ID: ISRCTN46017566 . Registered on 4 July 2014.