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-α therapy.
The phase III randomised controlled trial involved 391 patients with
active RA and an inadequate response to anti-TNF-α 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, plus 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 2005;353:11). |
The
Pharmaceutical Journal
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