In a recent clinical trial titled ’APIPPRA’, published in The Lancet, researchers revealed that early treatment with the T-cell co-stimulation modulator abatacept significantly delays the onset of rheumatoid arthritis (RA) in high-risk individuals. The study was conducted across multiple centers in the UK and the Netherlands and targeted participants identified by specific biomarkers and symptoms indicating the increased susceptibility to developing RA.
During the treatment phase, only 6% of those administered abatacept progressed to clinical synovitis or RA, compared to 29% in the placebo group. After the 24-month follow-up period, 25% of the participants in the abatacept group had progressed to RA, significantly lower than the 37% observed in the placebo group. Statistical analyses confirmed these findings, demonstrating a notable increase in arthritis-free survival time with abatacept, indicating its potential to alter the disease trajectory when administered proactively. At 24 months, the effects were not fully sustained, but the study indicates that using abatacept to modulate T-cell co-stimulation could be an effective strategy in preventing or delaying rheumatoid arthritis in at-risk populations. The overall safety profiles of the treatment were considered acceptable, which supports the potential of early therapeutic approaches for RA prevention.
Abatacept, also known as CTLA4Ig, is a fusion protein that consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc portion of human immunoglobulin 1 (IgG1). This medication works by inhibiting the activation of T lymphocytes, which are involved in the early stages of RA. Abatacept achieves this by binding to the costimulatory molecules CD80 and CD86 on antigen-presenting cells (APC), thereby preventing their interaction with CD28 on T cells. In addition to its primary mechanism of action, which involves blocking T-cell activation, abatacept also affects other cell populations such as regulatory T cells (Treg), monocytes/macrophages, osteoclasts, and B cells. Clinical studies have demonstrated the effectiveness of Abatacept in treating various autoinflammatory diseases, including RA.
The APIPPRA trial marks a significant advancement in rheumatology. It paves the way for future treatments aimed at stopping autoimmune diseases before the occurrence of irreversible damage. As research progresses, efforts are underway to refine treatment protocols and expand access to potentially transformative therapies like abatacept, offering renewed hope to millions worldwide who are at risk of developing RA. This research opens new avenues for preventing RA and emphasizes the importance of identifying and treating high-risk individuals before the disease fully onset. Further studies are needed to determine the long-term benefits and the optimal duration of treatment.
Reference
- Cope AP, Jasenecova M, Vasconcelos JC, Filer A, Raza K, Qureshi S et al; APIPPRA study investigators. Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial. Lancet. 2024 Mar 2;403(10429):838-849.
- Dubois EA, Cohen AF. Abatacept. Br J Clin Pharmacol. 2009 Oct;68(4):480-1.
- Bonelli M, Scheinecker C. How does abatacept really work in rheumatoid arthritis? Curr Opin Rheumatol. 2018 May;30(3):295-300.