Loading ...

BARCELONA, Spain — Treatment with abatacept delays the onset of rheumatoid arthritis (RA) in patients at high risk of developing the disease, according to data presented at the European Alliance of Associations for Rheumatology (EULAR) 2025 Annual Meeting.

Researchers presented long-term data from both the APIPPRA and ARIAA trials, with up to 9 years of follow-up. In both trials, the treatment effect of a time-limited intervention with abatacept lasted 4-5 years.

“The ARIAA and APIPPRA trials show that long-term follow-up is needed to evaluate whether or not RA is prevented,” said Annette H. van der Helm-van Mil, MD, PhD, professor of rheumatology at Leiden University Medical Center, Leiden, the Netherlands, commenting on the study for Medscape Medical News.

Initial results from both trials showed that patients treated with abatacept were less likely to develop RA up to 1 year after stopping the drug; however, “after prolonged follow-up, this difference disappeared.”

The two trials were independent, “but the results are more or less identical,” added Jürgen Rech, MD, of Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany, who led the ARIAA trial.

ALTO Study

Andrew Cope, MBBS, PhD, head of the Centre for Rheumatic Diseases at King’s College London, London, England, presented results from the ALTO study, building on the APIPPRA trial.

The APIPPRA trial enrolled 213 individuals who tested positive for anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) and had inflammatory joint pain; none had been diagnosed with RA. Individuals who were RF-negative but had ACPA concentrations at least three times the upper limit of normal were also included. Patients were randomly assigned to receive weekly subcutaneous injections of 125 mg abatacept or placebo for 1 year. During the treatment period, only 6% of patients treated with abatacept developed RA compared with 29% of the placebo group. The treatment was stopped after 1 year, and patients were followed for another year. Although the difference between the two groups narrowed at 24 months, the proportion of patients who had progressed to RA was still higher in the placebo group (37%) than in the abatacept group (25%).

For longer-term results, researchers enrolled 143 individuals who had participated in the APIPPRA trial and continued follow-up. The primary endpoint was time to development of either clinical synovitis in three or more joints or RA according to the American College of Rheumatology/EULAR 2010 classification criteria. The median follow-up time from the beginning of the APIPPRA trial (ie, randomization) was 66 months.

At 4 years of follow-up since the original trial began, the difference in RA progression between the placebo and abatacept groups disappeared.

The presence of the following serum autoantibodies was also linked to response: immunoglobulin G ACPA, immunoglobulin A ACPA, anti-carbamylated protein antibodies, anti-acetylated protein antibodies, and RF.

Patients with all five of these autoantibodies had better responses with abatacept, with differences between the treatment and placebo arms lasting up to 6 years after initiating time-limited treatment. Cope noted that patient numbers for this subgroup were small, with 23 in the abatacept arm and 27 in the placebo arm.

For participants with fewer than all five of these autoantibodies, including any combination of the five, “the abatacept and placebo [RA-free] survival curves basically cross and are almost superimposable from about month 18,” Cope said.

The ARIAA Trial

Koray Tascilar, MD, of Friedrich Alexander University of Erlangen-Nürnberg, presented the long-term follow-up results from the ARIAA trial.

The original trial enrolled 98 ACPA-positive individuals with joint pain and signs of osteitis, synovitis, or tenosynovitis on hand MRI and randomized them to receive weekly subcutaneous injections of 125 mg abatacept or placebo for 6 months. The primary endpoint was any reduction in inflammatory MRI lesions at 6 months, but the study also documented RA development based on physician diagnosis.

Researchers found that abatacept treatment decreased the risk of developing RA, with only 8% of the abatacept group developing RA compared with 35% of the placebo group through 6 months of treatment. Researchers observed accelerated RA development in the abatacept group after stopping treatment, but this trend leveled off by the end of 1 year of drug-free observation. At 18 months, 35% of the abatacept group and 57% of the placebo group had developed RA.

To find out how long this effect persisted, Tascilar and colleagues continued to follow patients, with a median follow-up time of 5.3 years.

Of the 53 patients who had not developed RA during the initial 18-month study, 25 were diagnosed with the disease during long-term follow-up: 17 from the abatacept group and 8 from the placebo group. Since the beginning of ARIAA, roughly 70% of patients in either group had developed RA.

The data revealed that the abatacept treatment effect persisted for up to 5 years. On average, abatacept provided 10 months of additional RA-free survival compared with placebo.

van der Helm-van Mil was skeptical about whether this 10-month delay would be clinically meaningful; Rech had a different perspective.

“We were able, with a short time of treatment, to delay the onset of disease,” Rech said, “which is pretty cool.”

Bristol Myers Squibb (BMS) funded the APIPPRA and ALTO studies, and the Innovative Medicines Initiative funded the original 18-month ARIAA study. Cope reported relationships with BMS, Galapagos, Janssen, UCB, AbbVie, Nucleome Therapeutics, Galvani, and Lilly. Rech reported receiving speaker or consultancy fees from AbbVie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD, Novartis, Roche, Sanofi, Sobi, and UCB. Tascilar reported receiving speaker fees from Novartis. van der Helm-van Mil reported having no relevant financial relationships.