Objectives and study design.
The primary objectives of this study were to compare immunologic responses, antibody persistence, safety and varicella breakthrough rates when VARIVAX® (varicella vaccine) is given at the same time as M-M-R®II (measles, mumps, rubella vaccine) and TETRAMUNE® (conjugate Haemophilus influenzae type b, diphtheria, tetanus and whole cell pertussis vaccine) at separate injection sites (Group A) vs. VARIVAX® given 6 weeks after M-M-R®II and TETRAMUNE® (Group B). Six hundred nine healthy children, 12 to 23 months of age, were randomized to one of two treatment (immunization) groups (Group A and Group B). Blood for antibody titers was drawn on the day of immunization, 6 weeks after each injection and 1 year later. Local and systemic adverse reactions were recorded. Exposure and cases of varicella were documented through a 1-year follow-up period.
Measles, mumps and rubella seroconversion rates and geometric mean titers (GMTs) were similar for both treatment groups. Varicella seroconversion rates were also similar between groups. However, varicella GMTs and percent with a varicella-protective level [≥5.0 glycoprotein (gp) enzyme-linked immunosorbent assay (ELISA) units] did not meet the prespecified criteria for similarity were lower for Group A (GMT 10.5; 82.8% ≥5.0 gp ELISA units) than for Group B (GMT 14.5; 91.2% ≥5.0 gp ELISA units). The GMTs between groups for other antibodies were similar. At the 1-year follow-up antibody titers were comparable in both groups and breakthrough varicella cases appeared generally similar. There were fewer local adverse events (AEs) at the VARIVAX® injection sites (9.8% and 2.9%, Group A and B, respectively) than at the TETRAMUNE® sites (27.9% and 24.0%). Systemic AEs were not statistically different when M-M-R®II was administered alone (8.6%) or concomitantly with VARIVAX® (8.9%). When VARIVAX® was given alone AEs were 1.8%. The rate of fever ≥102°F after M-M-R®II and TETRAMUNE® administered together was 10.7% on Days 0 to 3 and 23.7% on Days 7 to 21. When VARIVAX® was administered alone, the rate of fever was 5.4% on Days 0 to 3 (P = 0.018) and 10.8% on Days 7 to 21 (P < 0.001).
Because the varicella titers were comparable and varicella breakthrough rates generally similar at 1 year in both groups, we expect that the concomitant administration of VARIVAX® with M-M-R®II and TETRAMUNE® has clinical effectiveness similar to that with VARIVAX® 6 weeks after the administration of these other two vaccines. VARIVAX® appears to be less reactogenic than M-M-R®II and TETRAMUNE®.