A SINGLE DOSE OF ABATACEPT DOES NOT PREVENT THE DEVELOPMENT OF A POSITIVE IMMUNE RESPONSE TO TETANUS AND PNEUMOCOCCAL VACCINES

Background: The effect of abatacept (Aba), a selective T-cell co-stimulation modulator, on therapeutic vaccination has not been previously investigated. Full helper T-cell activation may be necessary for the generation of protective humoral responses to some types of vaccine.Objectives: To investigate the effects of a single infusion of Aba on antibody responses to 2 different types of vaccine: tetanus toxoid (primarily a memory response to a T cell-dependent peptidic antigen) and 23-valent pneumococcal vaccine (a less T cell-dependent response to polysaccharides).Methods: This single-dose, open-label study randomized 79 healthy volunteers equally to 1 of 4 treatment groups: 1) 0.5 mL intramuscular injections of tetanus toxoid and 23-valent pneumococcal vaccines given separately on Day 1; 2) vaccination 2 weeks pre-Aba (vaccines on Day 1 followed by a single 750 mg Aba infusion on Day 14); 3) vaccination 2 weeks post-Aba (Aba on Day 1 followed by vaccination on Day 14); and 4) vaccination 8 weeks post-Aba (Aba on Day 1 and vaccination on Day 56). Subjects were excluded if they had received any live vaccine within the prior 4 weeks, a tetanus booster or pneumococcal vaccine within 5 years, or had baseline (BL) anti-tetanus antibodies below clinically detectable levels. Anti-tetanus and anti-pneumococcal (Danish types 2, 6B, 8, 9V, 14, 19F and 23F) antibody titers were measured 14 and 28 days after vaccination. A positive response was defined as at least a 2-fold increase in antibody titer from BL. Safety and tolerability were assessed throughout the trial.Results: There was substantial inter-subject variability in both BL and post-BL titers in all groups. A positive response to tetanus vaccination at 28 days was seen in 75% of control subjects versus 63-70% of Aba-treated individuals (Table). Aba administration did not significantly inhibit a positive response to pneumococcal serotypes, with at least 70% of subjects responding to at least 3 serotypes, and 25-30% of subjects in all treatment groups responding to ≥6 serotypes. While there were no statistically significant differences between the dosing groups, the proportion of subjects responding to tetanus or pneumococcal vaccination was generally lower in subjects receiving the vaccines 2 weeks following Aba compared to control subjects. Apart from 1 SAE (an acute peri-infusional reaction, probably related to Aba), a single 750 mg dose of Aba appeared to be safe and well tolerated in this study. Treatment n BL mean tetanus, Responders Responders IU/mL (%CV) 2 weeks after 4 weeks after tetanus*, n (%) tetanus*, n (%) Vaccines/control 20 1.6 (106) 18 (90) 15 (75) Vaccines pre-Aba 20 1.9 (76) 16 (80) 13 (65) Vaccines 2 weeks post-Aba 19 2.3 (76) 11 (58) 12 (63) Vaccines 8 weeks post-Aba 20 2.3 (54) 16 (80) 14 (70) *Proportion of subjects achieving a 2-fold increase in antibody titer; n=19; CV=coefficients of variations.Conclusion: These preliminary data suggest that Aba does not significantly impair the ability of healthy subjects to respond to either tetanus or pneumococcal vaccination.References: Recommendations of the Immunization Practices Advisory Committee (ACIP) Update: Pneumococcal Polysaccharide Vaccine Usage - United States. Morb Mortal Wkly Rep 1984;33:273-81Citation: Ann Rheum Dis, volume 65, supplement II, year 2006, page 184Session: Rheumatic arthritis – treatment biologics