Abatacept halts RA progression early in high-risk group

Treatment with abatacept for a year halts disease progression in high-risk patients presenting with signs of imminent onset of rheumatoid arthritis (RA) in the phase IIb APIPPRA trial.

In this population, only seven of the 110 patients assigned to abatacept went on to develop clinical arthritis after a year compared with 30 of 103 in the placebo group (hazard ratio [HR], 0.20; p=0.0002).

However, the beneficial effect was cut short with discontinuation of abatacept after 1 year, reported Dr Andrew Cope from the King’s College London, London, UK.

Worse, 20 more patients in the abatacept group developed clinical arthritis the following year after abatacept was discontinued whereas 8 patients had it in the placebo group.

“Although the abatacept regimen maintained a significant advantage for the full 2 years (HR, 0.61; p=0.003), the Kaplan-Meier curves for arthritis-free survival were quickly converging near the end, making it appear that the abatacept group would catch up with additional follow-up,” said Cope. “Additionally, there were no safety problems seen with abatacept.”  

Hence, Cope said there seemed to be no reason for abatacept to be discontinued.

The goal of therapy

Stopping RA has been the goal of treatment for rheumatologists. Previous studies have supported early aggressive treatment once the disease is diagnosed. However, starting a biologic without a confirmed RA diagnosis is not recommended.

Nevertheless, some patients show up at arthritis clinics with a few painful joints and other features such as RA-related serum biomarkers that suggest progression to full-blown RA.

Can RA be stopped early?

This prompted Cope and colleagues to determine if RA can be stopped during its pre-clinical stage. They chose abatacept because the drug targets immune reactions early in the chain of events leading to inflammation in RA.

“It functions by interrupting the interaction between T cells and antigen-presenting cells, attenuating the co-stimulatory signals required for T-cell activation, differentiation and effector responses, thereby resulting in downstream immunomodulatory effects on other inflammatory cells of the immune system, he explained.

Patients from 31 sites in the UK and the Netherlands were included in the study if they had joint pain but without synovitis, who either tested positive for anti-citrullinated protein antigen (ACPA) antibodies and for rheumatoid factor (RF), or showed high levels of ACPA antibodies (more than thrice the upper limit of normal for the assay used) without RF. [EULAR 2023, abstract OP0130]

The primary endpoint of the study was development of clinically apparent arthritis in at least three joints or an RA diagnosis according to standard criteria.

Mean age of the patients was 48 years and 75 percent of the cohort were women. Majority had a history of smoking. Fewer than a third consumed more than five alcoholic drinks a week.

Baseline pain scores averaged about 24 on a 100-point scale. Almost all participants met the threshold for high ACPA antibody levels.

Benefits seen in high-risk group

Although the preventive effect seen in the primary analysis was not durable across the entire cohort, it appeared beneficial in the very high-risk subgroup. Forty-nine patients who had some level of IgG ACPA antibodies were also positive for a series of other biomarkers, including RF, IgA ACPA antibodies, anti-carbamylated protein antibodies, and anti-acetylated peptide antibodies.

In this subset of patients, only about 10 percent of those who had taken abatacept progressed to clinical arthritis at the end of 2 years compared with 50 percent of those assigned to placebo.