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 - PubMed (original) (raw)

doi: 10.1186/s13063-019-3403-7.

Marianna Jasenecova 2, Sonya Abraham 3, Aisla Bosworth 4, Ian N Bruce 5 6, Christopher D Buckley 7 8, Coziana Ciurtin 9, Maria-Antonietta D'Agostino 10 11, Paul Emery 12, Hill Gaston 13, John D Isaacs 14 15, Andrew Filer 7 8, Benjamin A Fisher 7 8, Thomas W J Huizinga 16, Pauline Ho 5 6, Clare Jacklin 4, Heidi Lempp 2, Iain B McInnes 17, Arthur G Pratt 14 15, Andrew Östor 13, Karim Raza 7 8, Peter C Taylor 18, Dirkjan van Schaardenburg 19, Dharshene Shivapatham 2, Alison J Wright 20, Joana C Vasconcelos 21, Joanna Kelly 22, Caroline Murphy 22, A Toby Prevost 21, Andrew P Cope 23

Affiliations

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 et al. Trials. 2019.

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.

Keywords: Abatacept; Antibodies to citrullinated protein antigens; At risk; Autoantibodies; Double-blind; Intervention; Placebo-controlled; Pre-clinical phase; Randomised; Rheumatoid arthritis.

PubMed Disclaimer

Conflict of interest statement

MA-L, MJ, SA, AB, CC, HG, AF, BAF, PH, CJ, HL, DvS, DS, AJW, JCV, JK, CM and ATP declare that they have no competing interests relating to this study. INB, CDB, M-AD’A, PE, TWJH, JDI, IBM, AÖ, AGP, KR, PCT, and APC have received honoraria, speaker fees or research funding (or a combination of these) from Bristol-Myers Squibb or from other pharmaceutical companies.

Figures

Fig. 1

Fig. 1

Study design and flow chart

Fig. 2

Fig. 2

Primary endpoint roadmap

Similar articles

Cited by

References

    1. Scott DL, Wolfe F, Huizinga TWJ. Rheumatoid arthritis. Lancet. 2010;376:1094–1108. doi: 10.1016/S0140-6736(10)60826-4. - DOI - PubMed
    1. Hochberg MC, Spector TD. Epidemiology of rheumatoid arthritis: update. Baillieres Clin Rheumatol. 1995;9:619–632. doi: 10.1016/S0950-3579(05)80305-X. - DOI - PubMed
    1. Wolfe F, Hawley DJ. The longterm outcomes of rheumatoid arthritis: Work disability: a prospective 18 year study of 823 patients. J Rheumatol. 1998;25:2108–2117. - PubMed
    1. Michaud K, Messer J, Choi HK, Wolfe F. Direct medical costs and their predictors in patients with rheumatoid arthritis: a three-year study of 7,527 patients. Arthritis Rheum. 2003;48:2750–2762. doi: 10.1002/art.11439. - DOI - PubMed
    1. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum. 2005;52:3381–3390. doi: 10.1002/art.21405. - DOI - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources