SAFETY, TOLERABILITY AND IMMUNOGENICITY OF CONCOMITANT INJECTIONS IN SEPARATE LOCATIONS OF M-M-R(R)(II), VARIVAX(R) AND TETRAMUNE(R) IN HEALTHY-CHILDREN VS. CONCOMITANT INJECTIONS OF M-M-R(R)(II) AND TETRAMUNE(R) FOLLOWED 6 WEEKS LATER BY VARIVAX(R)

Objectives and study design. The primary objectives of this study were to compare immunologic responses, antibody persistence, safety and va ricella breakthrough rates when VARIVAX (R) (varicella vaccine) is giv en at the same time as M-M-R-II(R) (measles, mumps, rubella vaccine) a nd TETRAMUNE (R) (conjugate Haemophilus influenzae type b, diphtheria, tetanus and whole cell pertussis vaccine) at separate injection sites (Group A) vs, VARIVAX (R) given 6 weeks after M-M-R-II(R) and TETRAMU NE (R) (Group B), Six hundred nine healthy children, 12 to 23 months o f age, were randomized to one of two treatment (immunization) groups ( Group A and Group B), Blood for antibody titers was drawn on the day o f immunization, 6 weeks after each injection and 1 year later. Local a nd systemic adverse reactions mere recorded, Exposure and cases of var icella were documented through a I-year follow-up period Results. Meas les, mumps and rubella seroconversion rates and geometric mean titers (GMTs) were similar for both treatment groups. Varicella seroconversio n rates were also similar between groups, However, varicella GMTs and percent with a varicella-protective level [greater than or equal to 5. 0 glycoprotein (gp) enzyme-linked immunosorbent assay (ELISA) units] d id not meet the prespecified criteria for similarity were lower for Gr oup A (GMT 10.5; 82.8% greater than or equal to 5.0 gp ELISA units) th an for Group B (GMT 14.5; 91.2% greater than or equal to 5.0 gp ELISA units), The GMTs between groups for other antibodies were similar. At the I-year follow-up antibody titers were comparable in both groups an d breakthrough varicella cases appeared generally similar. There were fewer local adverse events (AEs) at the VARIVAX (R) injection sites (9 .8% and 2.9%, Group A and B, respectively) than at the TETRAIMUNE (R) sites (27.9% and 24.0%). Systemic AEs were not statistically different when M-M-R-II(R) was administered alone (8.6%) or concomitantly with VARIVAX (R) (8.9%). When VARIVAX (R) was given alone AEs were 1.8%, Th e rate of fever greater than or equal to 102 degrees F after M-M-R-II( R) and TETRAMUNE (R) administered together was 10.7% on Days 0 to 3 an d 23.7% on Days 7 to 21, When VARIVAX (R) 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), Conclusion, Because the varicella titers were compa rable and varicella breakthrough rates generally similar at I year in both groups, we expect that the concomitant administration of VARIVAX (R) with M-M-R-II(R) and TETRAMUNE (R) has clinical effectiveness simi lar to that with VARIVAX (R) 6 weeks after the administration of these other two vaccines, VARIVAX (R) appears to be less reactogenic than M -M-R-II(R) and TETRAMUNE (R).