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Safety, tolerability and immunogenicity of concomitant injections in separate locations of M-M-R®II, VARIVAX® and TETRAMUNE® in healthy children vs. concomitant injections of M-M-R®II and TETRAMUNE® followed six weeks later by VARIVAX®

SHINEFIELD, HENRY R. MD; BLACK, STEVEN B. MD; STAEHLE, BRENDA O. MBA; ADELMAN, TAMA; ENSOR, KATHLEEN RN, BA; NGAI, ANGELA BS; WHITE, C. JO MD*; BIRD, STEVEN R. MS; MATTHEWS, HOLLY MS; KUTER, BARBARA J. PHD, MPH

Pediatric Infectious Disease Journal: November 1998 - Volume 17 - Issue 11 - pp 980-985
Original Studies

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.

Results. 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).

Conclusion. 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®.

From the Kaiser Permanente Vaccine Study Center, Oakland, CA (HRS, SBB, TA, KE), and the Merck Research Laboratories, West Point, PA (BOS, AN, SRB, HM, BJK).

Accepted for publication May 1, 1998.

*Current address: Aviron, Mountain View, CA.

Address for reprints: H. R. Shinefield, M.D., Co-Director Kaiser Pediatric Vaccine Study Center, Kaiser Permanente, 2200 O'Farrell Street, San Francisco, CA 94115. Fax 415-202-3566; E-mail henry.shinefield@ncal.kaiperm.org.

© Williams & Wilkins 1998. All Rights Reserved.