Preventive abatacept may delay RA diagnosis in at-risk populations

Upfront treatment with abatacept over 1 year delayed the onset of rheumatoid arthritis (RA) in individuals positive for anti-citrullinated protein antigens (ACPA) and rheumatoid factor (RF) with inflammatory joint pain. Continued observation revealed significantly reduced progression to RA up to 4 years.

The ALTO (ISRCTN12680338) follow-up study focused on the long-term outcomes of individuals at risk of RA who had received 1 year of abatacept or placebo as a preventive intervention during the phase 2b APIPPRA trial (EudraCT2013-003413-18) [1]. Prof. Andrew Cope (King's College London, United Kingdom) shared that in the APIPPRA study, 25% of participants in the abatacept arm progressed to RA versus 37% of those on placebo at 24 months, entailing an arthritis-free survival probability in favour of abatacept (log-rank test P=0.044) [2]. Despite a substantial reduction in rates of progression to RA, the arthritis-free survival curves converged at 2 years, prompting Prof. Cope to pose the question: “What happens beyond 2 years?”

To explore this, the ALTO study enrolled 143 of the original 213 APIPPRA participants, including 71 individuals who had received abatacept. The 3 co-primary endpoints consisted of the time to RA diagnosis (based on ACR/EULAR 2010 criteria), onset of clinical synovitis in ≥3 joints, or time to first disease-modifying anti-rheumatic drug (DMARD). The mean age was 48.2, 22% of individuals were male, and 60% were current or previous smokers. The median follow-up period was 66 months.

Results demonstrated that abatacept continued to provide benefit in the arthritis-free survival over placebo up to 3 (P=0.008) and 4 years (P=0.039), but not sustained at 5 years (P=0.102) (see Figure).

Patients who tested positive for all 5 autoantibodies, including IgM RF, IgA ACPA, IgG ACPA, anti-carbamylated, and anti- acetylated protein antibodies, had a higher likelihood of progressing to RA, but also showed greater responsiveness to abatacept. Prof. Cope also mentioned trends towards improvements in the secondary outcomes of Disease Activity Score (DAS)28-C-reactive protein (CRP) and EuroQol 5 Dimensions index in favour of abatacept.

In terms of safety, 10 serious adverse events in the abatacept and 12 in the placebo arms were reported, all deemed unrelated to the study drug. One fungal infection in the abatacept group was considered as possibly related to treatment. “One year of treatment with abatacept delays progression to RA for up to 4 years,” Prof. Cope concluded.

Figure: Kaplan-Meier curves illustrating arthritis-free survival in the APIPPRA and ALTO studies [1]

1. Abatacept in individuals at risk of developing rheumatoid arthritis: results from the Arthritis Prevention in the Pre-clinical Phase of RA with Abatacept Long Term Outcomes (ALTO) OP0004, EULAR 2025, 11–14 June, Barcelona, Spain.
2. Cope AP, et al. Lancet. 2024;403(10429):838-849.

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Posted on 8 August 202525 August 2025