See the established safety and demonstrated efficacy of PEDIARIX

The immunogenicity PEDIARIX offers2

Efficacy of PEDIARIX2

  • The efficacy of PEDIARIX is based on the immunogenicity of the individual antigens compared with licensed vaccines
  • Serological correlates of protection exist for the diphtheria, tetanus, hepatitis B, and poliovirus components
  • The efficacy of the pertussis component, which does not have a well-established correlate of protection, was determined in clinical trials of INFANRIX

Immunological Evaluation of PEDIARIX2

  • In a US multicenter study, infants were randomized to 1 of 3 groups
    • — A combination vaccine group that received PEDIARIX concomitantly at separate sites with Haemophilus influenzae type b (Hib) conjugate vaccine (Wyeth Pharmaceuticals Inc.; no longer licensed in the US) and US-licensed 7-valent pneumococcal conjugate vaccine (PCV7; Wyeth Pharmaceuticals Inc.; no longer available in the US)
    • — A separate vaccine group that received US-licensed INFANRIX (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed), ENGERIX-B [Hepatitis B Vaccine (Recombinant)], and inactivated poliovirus vaccine (IPV; Sanofi Pasteur SA) concomitantly at separate sites with the same Hib and PCV7 vaccines
    • — A staggered vaccine group that received PEDIARIX concomitantly at separate sites with the same Hib conjugate vaccine but with the same PCV7 vaccine administered 2 weeks later
  • Immunization schedule
    • — The schedule of administration was 2, 4, and 6 months of age
    • — Infants either did not receive a dose of hepatitis B vaccine prior to enrollment or were permitted to receive one dose of hepatitis B vaccine administered at least 30 days prior to enrollment
    • — For the separate vaccine group, ENGERIX-B was not administered at 4 months of age to subjects who received a dose of hepatitis B vaccine prior to enrollment
  • Immunological measures
    • — The immune responses to the pertussis (pertussis toxin [PT], filamentous hemagglutinin [FHA], and pertactin [PRN]), diphtheria, tetanus, poliovirus, and hepatitis B antigens were evaluated in sera obtained 1 month (range 20 to 60 days) after the third dose of PEDIARIX or INFANRIX
    • — The efficacy of the pertussis component, which does not have a well-established correlate of protection, was determined in clinical trials of INFANRIX
    • — Geometric mean antibody concentrations (GMCs) adjusted for prevaccination values for PT, FHA, and PRN and the seroprotection rates for diphtheria, tetanus, and the polioviruses among subjects who received PEDIARIX in the combination vaccine group, were shown to be noninferior to those achieved following separately administered vaccines
    • — Because of differences in the hepatitis B vaccination schedule among subjects in the study, no clinical limit for noninferiority was predefined for the hepatitis B immune response. However, in a previous US study, noninferiority of PEDIARIX relative to separately administered INFANRIX, ENGERIX-B, and an oral poliovirus vaccine, with respect to the hepatitis B immune response, was demonstrated
Antibody response against diphtheria, tetanus, pertussis, and polio in infants vaccinated at 2, 4, and 6 months of age2,*,†
  PEDIARIX,
Hib Vaccine, and PCV7
INFANRIX, ENGERIX-B,
IPV, Hib Vaccine, and PCV7
  (N=154-168) (N=141-155)
Anti-diphtheria Toxoid
% ≥0.1 IU/mL
99.4 98.7
Anti-tetanus Toxoid
% ≥0.1 IU/mL
100 98.1
Anti-pertussis Toxoid
% VR§
GMC
 
98.7
48.1
 
95.1
28.6
Anti-filamentous Hemagglutinin
% VR§
GMC
 
98.7
111.9
 
96.5
97.6
Anti-pertactin
% VR§
GMC
 
91.7
95.3
 
95.1
80.6
Anti-polio 1
% ≥1:8‡,║
100 100
Anti-polio 2
% ≥1:8‡,║
100 100
Anti-polio 3
% ≥1:8‡,║
100 100
Antibody response against hepatitis B in infants vaccinated at 2, 4, and 6 months of age2,*,†,#
  PEDIARIX,
Hib Vaccine, and PCV7
INFANRIX, ENGERIX-B,
IPV, Hib Vaccine, and PCV7
  (N=114-128) (N=111-121)
Anti-HBsAg
% ≥10 mIU/mL#
GMC (mIU/mL)#
 
97.7
1032.1
 
99.2
614.5
* Hib conjugate vaccine (Wyeth Pharmaceuticals Inc.; no longer licensed in the US); PCV7 (Wyeth Pharmaceuticals Inc.; no longer available in the US); IPV (Sanofi Pasteur SA).
Assay methods used: ELISA for anti-diphtheria, anti-tetanus, anti-PT, anti-FHA, anti-pertactin, and anti-HBsAg; microneutralization for anti-polio (1, 2, and 3).

VR=Vaccine response: in initially seronegative infants, appearance of antibodies (concentration ≥5 EL.U./mL); in initially seropositive infants, at least maintenance of prevaccination concentration.
GMC=Geometric mean antibody concentration. GMCs are adjusted for prevaccination levels.
One month blood sampling, range: 20 to 60 days.
Seroprotection rate or GMC for PEDIARIX not inferior to separately administered vaccines (upper limit of 90% CI on GMC ratio [separate vaccine group/combination vaccine group] <1.5 for anti-PT, anti-FHA, and anti-pertactin, and upper limit of 95% CI for the difference in seroprotection rates [separate vaccine group minus combination vaccine group] <10% for diphtheria and tetanus and <5% for the 3 polioviruses). GMCs are adjusted for prevaccination levels.
§ The upper limit of 95% CI for differences in vaccine response rates (separate vaccine group minus combination group) was 0.31, 1.52, and 9.46 for PT, FHA, and pertactin, respectively. No clinical limit defined for noninferiority.
Poliovirus neutralizing antibody titer.
Subjects who received a previous dose of hepatitis B vaccine were excluded from the analysis of hepatitis B seroprotection rates and GMCs presented in the table.
# No clinical limit defined for noninferiority.

PEDIARIX has an established safety profile2

Adverse Reactions: Clinical Trials Experience2

  • Because clinical trials are conducted under widely varying conditions, adverse event rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine, and may not reflect the rates observed in practice
  • A total of 23,849 doses of PEDIARIX have been administered to 8,088 infants who received one or more doses as part of the 3-dose series during 14 clinical studies
    • — Common adverse events that occurred in ≥25% of subjects following any dose of PEDIARIX included local injection-site reactions (pain, redness, and swelling), fever, drowsiness, irritability/fussiness, and loss of appetite
    • — In comparative studies, administration of PEDIARIX was associated with higher rates of fever relative to separately administered vaccines. The prevalence of fever was highest on the day of vaccination and the day following vaccination. More than 96% of episodes of fever resolved within the 4-day period following vaccination (ie, the period including the day of vaccination and the next 3 days)

US Safety Study2

  • In a US study, the safety of PEDIARIX was compared to the safety of separately administered INFANRIX (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed), ENGERIX-B [Hepatitis B Vaccine (Recombinant)], and inactivated poliovirus vaccine (IPV; Sanofi Pasteur SA) in infants
    • — PEDIARIX: N=673
    • — Separately administered vaccines: N=335
    • — In both groups, infants received Haemophilus influenzae type b (Hib) conjugate vaccine (Wyeth Pharmaceuticals Inc.; no longer licensed in the US) and 7-valent pneumococcal conjugate vaccine (PCV7; Wyeth Pharmaceuticals Inc.; no longer available in the US) concomitantly at separate sites
  • Dosing schedule: all vaccines were administered at 2, 4, and 6 months of age
  • Data collection:
    • — Solicited local reactions and general adverse events were collected by parents using standardized diary cards for 4 consecutive days following each vaccine dose (ie, day of vaccination and the next 3 days)
    • — Telephone follow-up conducted 1 month and 6 months after the third vaccination to inquire about serious adverse events
    • — At the 6-month follow-up, information also was collected on new onset of chronic illnesses. A total of 638 subjects who received PEDIARIX and 313 subjects who received INFANRIX, ENGERIX-B, and IPV completed the 6-month follow-up

Data on reported solicited adverse reactions by dose within 4 days of vaccination (day of vaccination and the next 3 days) with PEDIARIX or separately administered INFANRIX, ENGERIX-B, and IPV are shown in the following tables.

Percentage of infants with solicited local* adverse events within 4 days of vaccination at 2, 4, and 6 months of age (Modified Intent-to-Treat Cohort)2
  PEDIARIX, Hib Vaccine, and PCV7 INFANRIX, ENGERIX-B, IPV, Hib Vaccine, and PCV7
  Dose 1
(N=671)
Dose 2
(N=653)
Dose 3
(N=648)
Dose 1
(N=335)
Dose 2
(N=323)
Dose 3
(N=315)
Pain, any 36.1 36.1 31.2 31.9 30.0 29.8
Pain, Grade 2 or 3 11.5 10.9 10.6 9.0 8.7 8.9
Pain, Grade 3 2.4 2.5 1.7 2.7 1.5 1.3
   
Redness, any 24.9 37.2 40.1 18.2 32.8 39.0
Redness, >5 mm 6.0 9.6 12.7 1.8 5.9 7.3
Redness, >20 mm 0.9 1.2 2.8 0.3 0.0 1.9
   
Swelling, any 17.3 26.5 28.7 9.6 20.4 24.8
Swelling, >5 mm 5.8 9.6 9.3 1.8 5.0 4.1
Swelling, >20 mm 1.9 2.5 3.1 0.6 0.0 1.3
Percentage of infants with solicited general adverse events within 4 days of vaccination at 2, 4, and 6 months of age (Modified Intent-to-Treat Cohort)2
  PEDIARIX, Hib Vaccine, and PCV7 INFANRIX, ENGERIX-B, IPV, Hib Vaccine, and PCV7
  Dose 1
(N=667)
Dose 2
(N=644)
Dose 3
(N=645)
Dose 1
(N=333)
Dose 2
(N=321)
Dose 3
(N=311)
Fever§ (≥100.4°F) 27.9 38.8 33.5 19.8 30.2 23.8
Fever§ (>101.3°F) 7.0 14.1 8.8 4.5 9.7 5.8
Fever§ (>102.2°F) 2.2 3.6 3.4 0.3 3.1 2.3
Fever§ (>103.1°F) 0.4 1.4 1.1 0.0 0.3 0.3
Fever§ M.A. 1.2 0.2 0.8 0.0 0.6 0.0
  (N=671) (N=653) (N=648) (N=335) (N=323) (N=315)
Drowsiness, any 57.2 51.6 40.9 54.0 48.3 38.4
Drowsiness, Grade 2 or 3 15.8 13.8 11.4 17.6 12.4 11.1
Drowsiness, Grade 3 2.5 1.2 0.9 3.6 0.6 1.9
   
Irritability/Fussiness, any 60.5 64.9 61.1 61.5 61.6 56.5
Irritability/Fussiness, Grade 2 or 3 19.8 27.9 25.2 19.4 21.1 19.4
Irritability/Fussiness, Grade 3 3.4 4.4 3.5 3.9 3.4 3.2
   
Loss of appetite, any 30.4 30.6 26.2 27.8 26.6 23.8
Loss of appetite, Grade 2 or 3 6.6 7.8 5.9 5.1 3.4 5.4
Loss of appetite, Grade 3 0.7 0.3 0.2 0.6 0.3 0.0
  Haemophilus influenzae type b (Hib) conjugate vaccine (Wyeth Pharmaceuticals Inc.; no longer licensed in the US); pneumococcal 7-valent conjugate vaccine (PCV7; Wyeth Pharmaceuticals Inc.; no longer available in the US); inactivated poliovirus vaccine (IPV; Sanofi Pasteur SA).
  N=Number of infants for whom at least one symptom sheet was completed; for fever, numbers exclude missing temperature recordings or tympanic measurements.
M.A.=Medically attended (a visit to or from medical personnel).
  Grade 2 was defined as sufficiently discomforting to interfere with daily activities. Grade 3 was defined as preventing normal daily activities.
* Local reactions at the injection site for PEDIARIX or INFANRIX.
Within 4 days of vaccination, defined as day of vaccination and the next 3 days.
Rate significantly higher in the group that received PEDIARIX compared with separately administered vaccines (P value <0.05 [2-sided Fisher Exact test] or the 95% Confidence interval [CI] on the difference between groups [separate minus PEDIARIX] does not include 0).
§ Axillary temperatures increased by 1ºC and oral temperatures increased by 0.5ºC to derive equivalent rectal temperature.

Postmarketing Safety Surveillance Study2

  • A safety surveillance study was conducted at a US health maintenance organization (HMO)
  • Infants who received 1 or more doses of PEDIARIX (from mid-2003 through mid-2005) were compared with age-, gender-, and area-matched historical controls who received one or more doses of separately administered US-licensed DTaP vaccine from 2002 through approximately mid-2003
  • Only infants who received 7-valent pneumococcal conjugate vaccine (PCV7; Wyeth Pharmaceuticals Inc.; no longer available in the US) concomitantly with PEDIARIX or DTaP vaccine were included
  • Other US-licensed vaccines were administered according to routine practices at study sites. A birth dose of hepatitis B vaccine had been administered routinely to infants in the historical DTaP control cohort, but not to infants who received PEDIARIX
  • For each of doses 1-3, a random sample of 40,000 infants who received PEDIARIX was compared with the historical DTaP control cohort for the incidence of seizures (with or without fever) during the 8-day period following vaccination
  • For each dose, random samples of 7,500 infants in each cohort were also compared for the incidence of medically-attended fever (fever ≥100.4°F that resulted in hospitalization, an emergency department visit, or an outpatient visit) during the 4-day period following vaccination

The incidence of verified seizures and medically-attended fever from this study are shown in the following table.

Percentage of infants with seizures (with or without fever) within 8 days of vaccination and medically-attended fever within 4 days of vaccination2
  PEDIARIX Historical
DTaP controls
Difference
(PEDIARIX-DTaP controls)
N n %
(95% CI)
N n %
(95% CI)
%
(95% CI)
All seizures
(with or without fever)
             
Dose 1,
Days 0-7
40,000 7 0.02
(0.01, 0.04)
39,232 6 0.02
(0.01, 0.03)
0.00
(-0.02, 0.02)
Dose 2,
Days 0-7
40,000 3 0.01
(0.00, 0.02)
37,405 4 0.01
(0.00, 0.03)
0.00
(-0.02, 0.01)
Dose 3,
Days 0-7
40,000 6 0.02
(0.01, 0.03)
40,000 5 0.01
(0.00, 0.03)
0.00
(-0.01, 0.02)
Total Doses 120,000 16 0.01
(0.00, 0.02)
116,637 15 0.01
(0.01, 0.02)
0.00
(-0.01, 0.01)
Medically-attended fever*              
Dose 1,
Days 0-3
7,500 14 0.19
(0.11, 0.30)
7,500 14 0.19
(0.11, 0.30)
0.00
(-0.14, 0.14)
Dose 2,
Days 0-3
7,500 25 0.33
(0.22, 0.48)
7,500 15 0.20
(0.11, 0.33)
0.13
(-0.03, 0.30)
Dose 3,
Days 0-3
7,500 21 0.28
(0.17, 0.43)
7,500 19 0.25
(0.15, 0.39)
0.03
(-0.14, 0.19)
Total Doses 22,500 60 0.27
(0.20, 0.34)
22,500 48 0.21
(0.16, 0.28)
0.05
(-0.01, 0.14)
  DTaP was any US-licensed DTaP vaccine. Infants received 7-valent pneumococcal conjugate vaccine (Wyeth Pharmaceuticals Inc.) concomitantly with each dose of PEDIARIX or DTaP.
  Other US-licensed vaccines were administered according to routine practices at the study sites.
  N=Number of subjects in the given cohort.
  n=Number of subjects with events reported in the given cohort.
* Medically-attended fever defined as fever ≥100.4°F that resulted in hospitalization, an emergency department visit, or an outpatient visit.

For children at higher risk of seizures, an antipyretic may be administered at the time of vaccination with PEDIARIX.

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