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
Mariam Al-Laith,
Marianna Jasenecova,
Sonya Abraham,
Aisla Bosworth,
Ian N. Bruce,
Christopher D. Buckley,
Coziana Ciurtin,
Maria-Antonietta D’Agostino,
Paul Emery,
Hill Gaston,
John D. Isaacs,
Andrew Filer,
Benjamin A. Fisher,
Thomas W. J. Huizinga,
Pauline Ho,
Clare Jacklin,
Heidi Lempp,
Iain B. McInnes,
Arthur G. Pratt,
Andrew Östor,
Karim Raza,
Peter C. Taylor,
Dirkjan van Schaardenburg,
Dharshene Shivapatham,
Alison J. Wright,
Joana C. Vasconcelos,
Joanna Kelly,
Caroline Murphy,
A. Toby Prevost,
Andrew P. Cope
Affiliations
Mariam Al-Laith
Centre for Rheumatic Diseases, Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, Weston Education Centre
Marianna Jasenecova
Centre for Rheumatic Diseases, Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, Weston Education Centre
Sonya Abraham
Department of Rheumatology, National Institute for Health Research-Wellcome Clinical Research Facility
Aisla Bosworth
National RA Society, The Switchback Office Park
Ian N. Bruce
Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, Stopford Building, University of Manchester
Christopher D. Buckley
Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital
Coziana Ciurtin
Department of Adolescent and Adult Rheumatology, University College London Hospitals NHS Trust
Maria-Antonietta D’Agostino
Rheumatology Department, Hôpital Ambroise Paré
Paul Emery
Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, UK NIHR Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust
Hill Gaston
Department of Medicine, University of Cambridge and Addenbrookes Hospital NHS Trust
John D. Isaacs
Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University
Andrew Filer
Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital
Benjamin A. Fisher
Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital
Thomas W. J. Huizinga
Department of Rheumatology, Leiden University Medical Centre
Pauline Ho
Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, Stopford Building, University of Manchester
Clare Jacklin
National RA Society, The Switchback Office Park
Heidi Lempp
Centre for Rheumatic Diseases, Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, Weston Education Centre
Iain B. McInnes
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow
Arthur G. Pratt
Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University
Andrew Östor
Department of Medicine, University of Cambridge and Addenbrookes Hospital NHS Trust
Karim Raza
Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital
Peter C. Taylor
Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford
Dirkjan van Schaardenburg
Amsterdam Rheumatology and immunology Center, locations Reade and Amsterdam University Medical Center
Dharshene Shivapatham
Centre for Rheumatic Diseases, Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, Weston Education Centre
Alison J. Wright
Clinical, Education & Health Psychology Division of Psychology & Language Sciences, Faculty of Brain Sciences, University College London
Joana C. Vasconcelos
Imperial Clinical Trials Unit, School of Public Health, Imperial College London
Joanna Kelly
King’s Clinical Trials Unit, King’s College London, Institute of Psychiatry
Caroline Murphy
King’s Clinical Trials Unit, King’s College London, Institute of Psychiatry
A. Toby Prevost
Imperial Clinical Trials Unit, School of Public Health, Imperial College London
Andrew P. Cope
Centre for Rheumatic Diseases, Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, Weston Education Centre
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 co-stimulatory 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 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. 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 and 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 4 July 2014.
