(JM test 5)Abatacept may mitigate rheumatoid arthritis development in at-risk individuals

The use of abatacept in adults at high risk of rheumatoid arthritis (RA) helps protect against disease onset, as shown in the phase IIB APIPPRA study.

After 12 months of treatment, progression to RA (ie, clinical synovitis in at least three joints or an RA diagnosis) occurred less frequently with abatacept than with placebo (6 percent vs 29 percent). The estimated proportion of participants remaining arthritis-free at 12 months was 92.8 percent in the abatacept arm and 69.2 percent in the placebo arm. [Lancet 2024;doi:10.1016/S0140-6736(23)02649-1]

By 24 months, 25 percent of participants in the abatacept arm and 37 percent of those in the placebo arm had experienced the initial manifestation of RA, with the last 12 months being the off-treatment follow-up period.

Kaplan–Meier analysis indicated that participants on abatacept had a higher probability of remaining arthritis-free at 24 months compared with those on placebo (log-rank test, p=0.044). The average time participants in the abatacept vs placebo arm were expected to remain arthritis-free was 53 days longer (95 percent confidence interval [CI], 28–78; p<0.0001) at the 12-month mark and 99 days longer (95 percent CI, 38–161; p=0.0016) at the 24-month mark.

During the treatment period, abatacept was also associated with improvements in pain scores, functional wellbeing, and quality-of-life measurements, as well as low subclinical synovitis scores by ultrasonography, compared with placebo. However, these effects were not sustained at 24 months.

“This is the largest RA prevention trial to date and the first to show that a therapy licensed for use in treating established RA is also effective in preventing the onset of disease in people at risk,” according lead study author Prof Andrew Cope of King’s College London, London, UK.

“These initial results could be good news for people at risk of arthritis, as we show that the drug not only prevents disease onset during the treatment phase but can also ease symptoms such as pain and fatigue,” Cope said.

APIPPRA included 213 adults with serum antibodies to citrullinated protein antigens (ACPA), rheumatoid factor, and symptoms such as inflammatory joint pain. These participants were randomly assigned to receive subcutaneous injections of abatacept at 125 mg weekly or placebo for 12 months and then followed up for another 12 months.

In terms of safety, seven serious adverse events occurred in the abatacept group and 11 in the placebo group, including one death in each group deemed unrelated to treatment.

“There are currently no drugs available that prevent [RA, which is a] potentially crippling disease. Our next steps are to understand people at risk in more detail so that we can be absolutely sure that those at highest risk of developing RA receive the drug,” Cope said.

He emphasized the need for a long-term follow-up of the trial population to establish whether abatacept indeed prevents or only delays the progression of RA.