medwireNews: Use of abatacept in individuals at high risk for rheumatoid arthritis (RA) reduces the likelihood of developing clinically evident arthritis during the treatment period, suggest findings from the APIPPRA trial.
In this randomized phase 2b clinical trial, 6% of 110 participants treated with abatacept and 29% of 103 patients given placebo progressed to RA during 12 months of treatment. RA was classified as ultrasonography-confirmed synovitis in three or more joints or RA according to ACR/EULAR 2010 criteria.
By 24 months, the rates were 25% in the abatacept group and 37% in the placebo group, suggesting “sustained efficacy beyond the treatment period,” Andrew Cope and colleagues (King’s College London, UK) report in The Lancet.
In a comment accompanying the study, Annette van der Helm–van Mil (Leiden University Medical Centre, the Netherlands) highlights that “[a]batacept is currently estimated to be used in approximately 5% of patients with RA. However, use could increase 60-fold (to 300%) if abatacept is acceptable in the arthralgia at risk phase and approximately one third of ACPA [autoantibodies against citrullinated protein antigen]-positive patients with arthralgia progress to RA.”
The trial collated information for 213 patients (77% women, 82% White) aged a mean of 48.5 years from hospital-based early arthritis clinics in the UK and the Netherlands. The patients were considered at risk for RA due to having serum antibodies to ACPA and rheumatoid factor, and symptoms such as inflammatory joint pain.
The participants were randomly assigned to receive weekly subcutaneous abatacept 125 mg or placebo for 12 months followed by 12 months with no treatment. None of the patients had previously taken corticosteroids or disease-modifying antirheumatic drugs.
Using Kaplan–Meier survival curves, the researchers estimated that more patients in the abatacept than the placebo group were arthritis-free at 12 months (92.8 vs 69.2%) and 24 months (70.4 vs 58.5%), with the differences at 24 months significantly favoring abatacept, they report.
Furthermore, the study results showed that at both 12 and 24 months, patients treated with abatacept remained free of arthritis for significantly longer, with differences of 53 days and 99 days, respectively.
The results were similar in a per-protocol analysis which considered only treatment-compliant individuals (received 90% of injections and no rescue medication), with a 114-day difference in mean arthritis-free survival at 24 months in favor of abatacept.
“In-depth analysis of patient-reported outcomes reveals that the symptom burden characteristic of ACPA-positive individuals with arthralgia is driven, at least in part, by systemic adaptive immune responses targeted by abatacept,” say the researchers.
The results showed significant benefits with abatacept relative to placebo at 12 months for pain and function on the Health Assessment Questionnaire, emotional wellbeing and quality of life on the EQ-5D, anxiety on the Hospital Anxiety and Depression Scale, and Functional Assessment of Chronic Illness Therapy–Fatigue total score, as well as no or low levels of detectable subclinical synovitis on ultrasonography. However, these effects were not sustained at 24 months.
Adverse events (AEs) occurred in 92% of 109 participants who received at least one dose of abatacept and in 89% of 102 in the placebo group, with at least one infection occurring in a respective 52% and 61%.
There were 18 serious AEs – seven in the abatacept group and 11 in the placebo group. Common events were cardiovascular events, admission for joint replacement surgery, and malignancy, and there was one death in each group, with the addition of three infections and one case of venous thromboembolism in the placebo group. None of the events were deemed to be related to study medication.
The findings show the “positive effect” of T-cell costimulation inhibition with abatacept during the arthralgia phase, say Cope et al. They suggest that abatacept might be required beyond 12 months to sustain efficacy longer term or need to be given intermittently, an option that “remains to be assessed.”
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