RA onset delayed through 4 years with 1-year abatacept treatment in at-risk individuals

A 12-month therapeutic intervention with self-administered abatacept can delay the onset of rheumatoid arthritis (RA) in at-risk individuals for up to 4 years, according to results from the ALTO follow-up study presented at EULAR 2025.

At 4 years of follow-up, individuals who were randomized to receive subcutaneous abatacept in the parent phase IIb trial had a significant 5-month delay in the mean time to progression to RA vs placebo recipients (restricted mean, 34 vs 29 months; p=0.039).

This difference in ‘arthritis-free’ survival was sustained since the 2-year follow-up, when the study continued as ALTO. Up to year 2, individuals who had been treated with abatacept for the first year had a mean delay of 3.3 months in the development of clinical arthritis vs placebo-treated individuals (restricted mean, 21.4 vs 18 months; p=0.001). At the 3-year point, the delay was 4.4 months (restricted mean, 28.4 vs 23.9 months; p=0.008). [EULAR 2025, abstract OP0004]

“[The] separation between the two survival curves [remained] beyond the 2-year period, but the curves converged and crossed over after 4 years,” said Professor Andrew Cope from King’s College London, Centre for Rheumatic Diseases, London, UK. “The statistics suggest that there were significant differences in survival times between the arms in favour of abatacept up to 4 years.”

Thereafter, the mean arthritis-free survival was similar between individuals treated with abatacept and those treated with placebo at year 5, when the study drug had been discontinued for 4 years (restricted mean, 38.6 vs 33.4 months; p=0.102).

“We undertook the ALTO long-term outcome study to capture the impact of disease beyond the 12-month treatment period,” concluded Cope. “A 1-year treatment with abatacept delays progression to RA for up to 4 years.”

Second- to fourth-year follow-up

ALTO succeeded the 24-month APIPPRA trial and continued to capture long-term outcomes in 143 participants for up to 6 years of follow-up.

The parent trial was a randomized, double-blind, placebo-controlled study (n=213) conducted in the UK and the Netherlands. Participants were adults presenting with inflammatory arthralgia who tested positive for anticitrullinated protein antibodies (ACPA), but without clinical synovitis at baseline. [Lancet 2024;403:838-849]

The primary endpoint of arthritis-free survival in the ALTO analysis was defined as the time to the first event of either development of clinically apparent synovitis in at least three joints, fulfilment of the classification criteria for RA, or initiation of the first disease-modifying antirheumatic drug.

At year 2, when ALTO began, the rates of meeting the primary endpoint in individuals in the abatacept vs placebo arms were 24.5 percent vs 37.9 percent (difference, 13.3 percentage points). The corresponding rates at year 3 were 38.2 percent vs 49.5 percent (difference, 11.3 percentage points), and at year 4 were 43.6 percent vs 54.4 percent (difference, 10.7 percentage points). Thus, the numbers needed to treat with abatacept to prevent one progression to RA at years 2, 3, and 4, were 7, 9, and 9, respectively.

In the placebo arm, 57.3 percent of individuals developed clinical arthritis at year 5 and 59.2 percent at year 6, showing a more gradual increase in the event rate from year 4 onwards.

“The survival curves tend to plateau at around 4 years,” said Cope on the data informing the natural history of RA. “Over 6 years, approximately 60 percent of at-risk, ACPA-positive, arthralgic individuals would progress to RA.”