Antirheumatic drug with novel mechanism of action

Abatacept, the first in a new class of antirheumatic drugs called selective co-stimulation modulators, appears to offer pain relief and increased mobility in rheumatoid arthritis patients, US researchers say.

Abatacept has a novel mechanism of action. It works by selectively modulating the CD80- or CD86-CD28 co-stimulatory signal required for full T-cell activation. The researchers say that by modulating events “upstream” of T-cell activation, abatacept has the potential to affect multiple pathways further down. “Our data suggest that, in addition to playing a key role in the activation of naive T-cells that orchestrate early disease, co-stimulation continues to play a role in the pathogenesis of established, long-standing disease,” they add.

The researchers believe that, given the novel mechanism of action of abatacept and the recognised role of T-cells in rheumatoid arthritis, selective modulation of co-stimulation represents a rational therapeutic approach in patients with an inadequate response to anti-TNF-a therapy.

The phase III randomised controlled trial involved 391 patients with active RA and an inadequate response to anti-TNF-a therapy. Patients received either abatacept (n=258) or placebo (n=133) on days 1, 15 and 29, and every 28 days after that for six months, at least one other disease-modifying antirheumatic drug.

Results showed that the number of patients reaching a clinical improvement of at least 20 per cent (ACR20) at six months was higher in the abatacept than in the placebo group (50.4 per cent versus 19.5 per cent; P<0.001). Improvement was evident at day 15 and increased over the study period with ACR50 and ACR70 being higher in the abatacept group at six months (P<0.001 and P=0.003, respectively).

In addition, more patients in the abatacept group had clinically meaningful improvements in physical function (47.3 per cent versus 23.3 per cent; P<0.001) and in health-related quality of life (New England Journal of Medicine ).

Citation: The Salvadore URI: 10019039

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