Browse by author
Lookup NU author(s): Professor John IsaacsORCiD, Dr Arthur PrattORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Background Clinical trials aimed at preventing rheumatoid arthritis in individuals at risk have had variable results. The long-term outcomes of disease interception, however, are not known. We aimed to examine the long-term effect of therapeutic intervention, with emphasis on efficacy and safety. Methods The Arthritis Prevention In the Preclinical Phase of Rheumatoid arthritis with Abatacept (APIPPRA) phase 2b, randomised controlled trial recruited 213 anti-citrullinated protein antibody (ACPA) positive individuals with arthralgia in 28 hospital-based early arthritis clinics in the UK and three in the Netherlands, randomly assigning participants to 52 weekly subcutaneous injections of 125 mg abatacept (n=110) or placebo (n=103), with another 52 weeks of follow-up. The APIPPRA Long-Term Outcome (ALTO) study extended follow-up for between 4 and 8 years and study participants and clinical assessors remained masked to treatment group. The primary outcome was the time from randomisation to development of clinical synovitis in at least three joints, rheumatoid arthritis according to American College of Rheumatology–European Alliance of Associations for Rheumatology 2010 criteria, or first treatment with disease modifying anti-rheumatic drugs, whichever was met first. The primary outcome was also stratified by autoantibody profiles defined at the time of randomisation. People with lived experience of rheumatoid arthritis had input into the APIPPRA study design. The study was registered at ISRCTN (ISRCTN-12680338), and is completed. Findings Between April 26, 2021, and Jan 31, 2023, 143 APIPPRA study participants enrolled in ALTO: 71 in the abatacept group and 72 in the placebo group (mean age 48·2 years [SD 11·2], 112 [78%] females, 31 [22%] males, 116 [81%] White). Median follow-up time from randomisation was 55 months (IQR 23–74). Primary events increased by 54 to 119. The initial between-group difference in restricted mean arthritis-free survival time observed at 2 years in APIPPRA remained significant at 4 years (4·9 months 95% CI 0·1–9·6; p=0·044), although the magnitude of this difference diminished over time. Assessments of disease activity and patient reported outcomes revealed no significant differences between groups beyond the treatment period. However, although participants with a broad autoantibody profile at baseline were at highest risk of progressing, this subgroup responded better to abatacept. There were 18 serious adverse events in the abatacept group and 13 in the placebo group; none deemed related to study drug. Interpretation In this at-risk population, 1-year treatment with abatacept delayed progression to rheumatoid arthritis for up to 4 years. Those at highest risk of progression have a broad autoantibody profile but are more responsive to abatacept treatment. Funding Bristol Myers Squibb.
Author(s): Cope AP, Jasenecova M, Vasconcelos JC, Qureshi S, van Schie KA, Filer A, Raza K, D'Agostino MA, McInnes IB, Siebert S, Isaacs JD, Pratt AG, Fisher BA, Buckley CD, Emery P, Mankia K, Ho P, Buch MH, Ciurtin C, van Schaardenburg D, Huizinga TWJ, Toes REM, Georgiou E, Kelly J, Murphy C, Prevost AT, Norton S, Opena M, Subesinghe S, Garrood T, Menon B, Ng N, Douglas K, Koutsianas C, Cooles F, Falahee M, Nelson M, Bharadwaj A, Ramos A, Thomas J, Pande I, Collins D, Pegler S, Raizada S, Fragoulis G, Taylor Gotch R, Galloway J, Rutherford A, Barnes T, Jeffrey H, Patel Y, Batley M, O'Reilly B, Venkatachalam S, Sheeran T, Gorman C, Reynolds P, Khan A, Gullick N, Banerjee S, Schenker N, Rowlands J, Starmans-Kool M, Taylor J, Nandi P, Sahbudin I, Maybury M, Hider S, Barcroft A, McNally J, Kitchen J, Nisar M, Quick V
Publication type: Article
Publication status: Published
Journal: The Lancet Rheumatology
Year: 2026
Volume: 8
Issue: 3
Pages: e171-e180
Online publication date: 20/01/2026
Acceptance date: 02/04/2018
Date deposited: 09/03/2026
ISSN (electronic): 2665-9913
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/S2665-9913(25)00371-6
DOI: 10.1016/S2665-9913(25)00371-6
Data Access Statement: Reasonable requests for data can be submitted to the corresponding author and will be considered on an individual basis.
Altmetrics provided by Altmetric
