Abstract
The effect of abatacept, a selective T-cell co-stimulation modulator, on vaccination has not been previously investigated. In this open-label, single-dose, randomized, parallel-group, controlled study, the effect of a single 750 mg infusion of abatacept on the antibody response to the intramuscular tetanus toxoid vaccine (primarily a memory response to a T-cell-dependent peptide antigen) and the intramuscular 23-valent pneumococcal vaccine (a less T-cell-dependent response to a polysaccharide antigen) was measured in 80 normal healthy volunteers. Subjects were uniformly randomized to receive one of four treatments: Group A (control group), subjects received vaccines on day 1 only; Group B, subjects received vaccines 2 weeks before abatacept; Group C, subjects received vaccines 2 weeks after abatacept; and Group D, subjects received vaccines 8 weeks after abatacept. Anti-tetanus and anti-pneumococcal (Danish serotypes 2, 6B, 8, 9V, 14, 19F and 23F) antibody titers were measured 14 and 28 days after vaccination. While there were no statistically significant differences between the dosing groups, geometric mean titers following tetanus or pneumococcal vaccination were generally lower in subjects who were vaccinated 2 weeks after receiving abatacept, compared with control subjects. A positive response (defined as a twofold increase in antibody titer from baseline) to tetanus vaccination at 28 days was seen, however, in ≥ 60% of subjects across all treatment groups versus 75% of control subjects. Similarly, over 70% of abatacept-treated subjects versus all control subjects (100%) responded to at least three pneumococcal serotypes, and approximately 25–30% of abatacept-treated subjects versus 45% of control subjects responded to at least six serotypes.
Highlights
Treatment with abatacept has demonstrated efficacy in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate, and in those with an inadequate response to anti-TNF therapy [1,2,3]
While there were no statistically significant differences between the dosing groups, geometric mean titers following tetanus or pneumococcal vaccination were generally lower in subjects who were vaccinated 2 weeks after receiving abatacept, compared with control subjects
Abatacept is the first in a class of agents for the treatment of RA that selectively modulates the CD80/CD86:CD28 co-stimulatory signal required for full T-cell activation [4]
Summary
Treatment with abatacept has demonstrated efficacy in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate, and in those with an inadequate response to anti-TNF therapy [1,2,3]. Abatacept is the first in a class of agents for the treatment of RA that selectively modulates the CD80/CD86:CD28 co-stimulatory signal required for full T-cell activation [4]. Activation of T cells usually requires two signals from antigen-presenting cells [5,6]. The first signal is mediated through the T-cell receptor via an interaction with major histocompatibility complex-presented peptide antigen [6]. The second, or co-stimulatory, signal is delivered following the engagement of CD80/CD86 on antigen-presenting cells with a cognate receptor, CD28, on the surface of the T cell [6,7]. A selective co-stimulation modulator, inhibits CD28-dependent T-cell activation by binding to CD80 and CD86 [4]
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