Abatacept May Delay Progression from At-Risk to Rheumatoid Arthritis

Abatacept may delay progression to rheumatoid arthritis (RA) in an at-risk population for several years, data from a long-term follow-up study suggest, although benefits may be minimal after 1-2 years.¹

The APIPPRA Long-Term Outcome (ALTO) study extended follow-up for 4-8 years from the original phase 2b Arthritis Prevention In the Preclinical Phase of Rheumatoid arthritis with Abatacept (APIPPRA) randomized controlled trial conducted in Europe. The primary outcome was meeting 1 of 3 indicators of RA: time from randomization to development of clinical synovitis in at least 3 joints, RA according to American College of Rheumatology (ACR) –European Alliance of Associations for Rheumatology 2010 criteria, or first treatment with disease modifying anti-rheumatic drugs (DMARD).

“Intervening early in people at high risk of RA can have lasting benefits. We have shown that this approach is safe and can prevent disease while patients are on treatment as well as substantially relieve symptoms. Importantly, it can also delay the onset of RA for several years, even after treatment has stopped. This could reduce how long people live with symptoms and complications, drastically improving their quality of life,” study investigator Andrew P Cope, MD, Professor, Centre for Rheumatic Diseases, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, said in statement.²

ALTO enrolled 143 APIPPRA study participants from ALTO between April 2021 and January 2023, 71 in the abatacept group and 72 in the placebo group. Participants had a mean age of 48.2 years (standard deviation [SD], 11.2), 112 were female (78%), and 116 (81%) were White. Participants had a median follow-up time of 55 months (IQR, 23–74) from randomization.¹

During ALTO, primary events increased by 54 to 119. Cope and colleagues found that 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 =.044), although between-group differences quickly dwindled to become insignificant. Furthermore, investigators found no significant differences on assessments of disease activity and patient reported outcomes between groups beyond the treatment period.¹

“Cope and colleagues conclude that abatacept delays the development of rheumatoid arthritis for up to 4 years. However, if using the outcome of time to first DMARD, then the protective effect seemed to be lost after 1 year of stopping abatacept as 39% in the abatacept group and 46% in the placebo group at 2 years post-randomization (abatacept was numerically better), but thereafter the proportions requiring a DMARD were the same. After 2 years, events of rheumatoid arthritis appeared the same beyond the initial protective effect of abatacept,” Janet E. Pope, MD, MPH, Professor of Medicine and member of the Division of Rheumatology at the University of Western Ontario, wrote in an editorial.³

At the end of 6 years of follow-up, 29% of all at-risk individuals enrolled in the APIPPRA trial had not progressed to RA. Cope and colleagues pointed to a group of highest-risk participants with a broad autoantibody profile at baseline as being better responders to abatercept. Safety outcomes were similar between groups, with 18 serious adverse events (AEs) in the abatacept group and 13 in the placebo group and none deemed related to study drug.¹

“This study improves the understanding of who might develop synovitis or rheumatoid arthritis among the population of ACPA positive patients with arthralgia. Perhaps future trials should target only those at highest risk of developing RAwho are strongly ACPA positive, especially if other RA-associated autoantibodies are present. We have learned that when treatment is stopped, the preventive effects do wear off, but what we do not know is whether abatacept-exposed patients who eventually develop rheumatoid arthritis will in the future have a milder disease course or not,” Pope wrote.³

Cope and colleagues encouraged further research to refine the at-risk state with more precision, as well as to investigate a wider range of therapeutic targets extending beyond the existing armamentarium of disease modifying therapies used to treat established RA in people at risk for RA.¹

“The cost-effectiveness of temporarily treating people who do not have a chronic disease to prevent the onset of rheumatoid arthritis, which is a lifelong potentially disabling condition, is unknown. We are uncertain whether periodic treatment could be effective, such as following ACPA titers and re-treating for a period if ACPA became more strongly positive. Precise predictors of rheumatoid arthritis development are uncertain,” Pope concluded.³

References

1. Cope AP, Jasenecova M, Vasconcelos JC, et al. Long-term outcomes of abatacept in individuals at risk of developing rheumatoid arthritis (ALTO): a randomised, double-blind, placebo-controlled trial. Lancet Rheumatol. Published online January 20, 2026. Accessed January 21, 2026. DOI: 10.1016/S2665-9913(25)00371-6

2. Early treatment can delay rheumatoid arthritis for years. News release. King’s College London. January 20, 2026. Accessed January 21, 2026. https://www.eurekalert.org/news-releases/1113191

3. Pope JE. Can we prevent the onset of rheumatoid arthritis in patients with high-risk features? Lancet Rheumatol. Published online January 20, 2026. Accessed January 21, 2026. DOI: 10.1016/S2665-9913(26)00006-8