Proven efficacy and safety

Prevnar 13®PROVEN  in CAPiTA (Community-Acquired Pneumonia Immunization Trial in Adults)—one of the largest randomized prospective adult vaccine trials ever conducted2,3
84,496 immunocompetent adults aged 65 and older2
  • Double-blind, randomized, parallel-group, placebo-controlled vaccine efficacy trial comparing Prevnar 13® (Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM197 Protein]) (n=42,240) vs placebo (n=42,256)2,4
    Median duration of follow-up for both groups was 3.93 years4
    42.3% of subjects had pre-existing medical conditions, including heart disease (25.4%), lung disease or asthma (15.1%), and type 1 and type 2 diabetes mellitus (12.5%). 12.3% of subjects reported smoking at baseline4
    Surveillance conducted at 59 sites throughout the Netherlands2
    Adults with immunocompromising conditions or receiving immunosuppressive therapy and adults residing in a long-term care facility or requiring semiskilled nursing care were excluded4
Primary objective2
Demonstrate the efficacy of Prevnar 13® in the prevention of a first episode of confirmed vaccine-type pneumococcal community-acquired pneumonia (CAP)
 
 
 
 
Secondary objectives2
Demonstrate the efficacy of Prevnar 13® in the prevention of a first episode of confirmed nonbacteremic/noninvasive vaccine-type pneumococcal CAP
Demonstrate the efficacy of Prevnar 13® in the prevention of a first episode of vaccine-type invasive pneumococcal disease (IPD)
Trial description
CAPiTA (Community-Acquired Pneumonia Immunization Trial in Adults) Description2,4
A double-blind, randomized, parallel-group, controlled efficacy trial comparing Prevnar 13® (Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM197 Protein]) vs placebo was conducted in 84,496 community-dwelling adults aged 65 and older (mean age 72.8 ± 5.7 years) across 59 sites in the Netherlands. 42,240 subjects were vaccinated with Prevnar 13® and 42,256 subjects were vaccinated with placebo. Median duration of follow-up for both groups was 3.93 years. Surveillance for suspected pneumonia and IPD began immediately after vaccination and continued through identification of a prespecified number of cases.2,4
42.3% of subjects had pre-existing medical conditions, including heart disease (25.4%), lung disease or asthma (15.1%), and type 1 and type 2 diabetes mellitus (12.5%). 12.3% of subjects reported smoking at baseline.4
Inclusion/Exclusion Criteria2
  • Subjects aged 65 years or older who were registered with a general practitioner referring patients to the trial were eligible for inclusion
  • Subjects were excluded from the trial if they had previously received a pneumococcal vaccine, used an investigational vaccine or medication within 30 days prior to vaccination, resided in a nursing home or other institution, required semiskilled nursing care, were contraindicated for vaccination with Prevnar 13® or influenza vaccine, had a history of severe adverse reaction to a vaccine or vaccine component, or had an immune deficiency or suppression. Subjects who had a CAP or IPD episode with symptom onset less than 14 days after vaccination were excluded from all analyses
Trial End Points2
  • The primary end point was prevention of a first episode of confirmed vaccine-type CAP, defined as the presence of ≥2 prespecified clinical criteria, findings on chest radiography consistent with CAP, and a positive vaccine-type–specific urinary antigen test or isolation of vaccine-type Streptococcus pneumoniae from blood or another sterile site
  • The secondary end point of nonbacteremic/noninvasive vaccine-type CAP was defined as prevention of a first episode of vaccine-type CAP for which the result of a blood culture and results of cultures of any other sterile site were negative for S. pneumoniae
  • The secondary end point of vaccine-type IPD was defined as prevention of a first episode of vaccine-type IPD in which the presence of S. pneumoniae is detected in a sterile site
 
Prevnar 13®PROVEN  to help protect against pneumococcal pneumonia and IPD in adults aged 65 and older2
  • Prevnar 13® (Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM197 Protein]) provided a statistically significant reduction in 3 end points
Primary end point:
46%
(95.2% confidence interval [CI], 21.8-62.5)
STATISTICALLY SIGNIFICANT RISK REDUCTION
of a first episode of either vaccine-type nonbacteremic/noninvasive or vaccine-type bacteremic/invasive pneumococcal CAP
(Number of episodes: Prevnar 13® n=49; placebo n=90)
Secondary end points:
45%
(95.2% CI, 14.2-65.3)
STATISTICALLY SIGNIFICANT RISK REDUCTION
of a first episode of vaccine-type nonbacteremic/noninvasive pneumococcal CAP
(Number of episodes: Prevnar 13® n=33; placebo n=60)
75%
(95% CI, 41.4-90.8)
STATISTICALLY SIGNIFICANT RISK REDUCTION
of a first episode of vaccine-type IPD
(Number of episodes: Prevnar 13® n=7; placebo n=28)
  • The median duration of follow-up was 3.93 years4
 
From the CAPiTA (Community-Acquired Pneumonia Immunization Trial in Adults) study, for a subset of 2011 subjects (1006 Prevnar 13® and 1005 placebo recipients), solicited adverse reactions were monitored by recording local and systemic events using electronic diaries for 7 days after vaccination. Unsolicited adverse events were collected for 28 days after vaccination.4
 
Please click through the tabs in order to view the safety and effectiveness story*
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1. Local adverse events

Prevnar 13® incidence of local adverse events compared with placebo4
*Number of subjects with known values.
Statistically significant difference, P<0.05. No adjustments for multiplicity.

2. Systemic adverse events

Prevnar 13® incidence of systemic adverse events compared with placebo4
*Number of subjects with known values.
Statistically significant difference, P<0.05. No adjustments for multiplicity.

3. Incidence of fever

Prevnar 13® incidence of fever compared with placebo4
*Number of subjects with known values.
Statistically significant difference, P<0.05. No adjustments for multiplicity.

4. Real-world effectiveness data

Studied in a real-world patient population
Test-negative design (TND): a well-established measure of vaccine effectiveness5
  • Minimizes bias caused by differences among cases and controls
  • Helps to ensure a representative patient population
  • Commonly used to assess vaccine effectiveness
Study limitations5
  • Observational in nature
  • Low Prevnar 13® (Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM197 Protein]) uptake in study population (~14%)
  • Serotype-specific vaccine effectiveness and stratified analyses not possible
  • May be susceptible to selection bias or confounding factors
  • Overall number of CAP cases was relatively small (n=68)
CAP surveillance study population5
Adults 18+ admitted for CAP at 1 of 9 hospitals in Louisville, Kentucky
Real-world effectiveness study population5
  • Immunocompromised patients were included in the RWE study population, but were not studied in CAPiTA
  • Adults 65+ with CAP and pneumococcal vaccination history confirmed by EHR enrolled between April 2015 and April 2016 (N=2034)
Efficacy results from the CAPiTA RCT were confirmed by a RWE study2,5
The RWE study was conducted as a nested case-control study in US patients using a test-negative design (TND) (N=2034)5
CAPiTA PRIMARY END POINT2
of a first episode of either vaccine-type nonbacteremic/noninvasive or vaccine-type bacteremic invasive pneumococcal CAP (Number of episodes: Prevnar 13® n=49; placebo n=90)
(95.2% CI, 21.8-62.5)
RWE PRIMARY END POINT5
of vaccine-type CAP hospitalization5
(95% CI, 12.8-91.5)
COMORBID CONDITIONS5
88% of patients had ≥1 comorbid condition that increased their risk5
Study limitations5
  • Observational in nature
  • Low Prevnar 13® (Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM197 Protein]) uptake in study
  • Serotype-specific vaccine effectiveness and stratified analyses not possible
  • May be susceptible to selection bias or confounding factors
  • Overall number of CAP cases was relatively small (n=68)
 
  • Prevnar 13® will only help protect against S. pneumoniae serotypes in the vaccine
CAP=community-acquired pneumonia; CI=confidence interval; RCT=randomized controlled trial; RWE=real-world effectiveness.
ACIP=Advisory Committee on Immunization Practices; CDC=Centers for Disease Control and Prevention.
The safety of Prevnar 13® was evaluated in 6 safety and immunogenicity studies and 1 efficacy study4
 
References:
  1. Matanock A, Lee G, Gierke R, Kobayashi M, Leidner A, Pilishvili T. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among adults aged ≥65 years: updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2019;68:1069-1075. doi: http://dx.doi.org/10.15585/mmwr.mm6846a5.
  2. Bonten MJM, Huijts SM, Bolkenbaas M, et al. Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N Engl J Med. 2015;372(12):1114-1125.
  3. Hak E, Grobbee DE, Sanders EAM, et al. Rationale and design of CAPITA: a RCT of 13-valent conjugated pneumococcal vaccine efficacy among older adults. Neth J Med. 2008;66(9):378-383.
  4. Prevnar 13® (Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM197 Protein]) Prescribing Information, Wyeth Pharmaceuticals LLC, 2019.
  5. McLaughlin JM, Jiang Q, Isturiz RE, et al. Effectiveness of 13-valent pneumococcal conjugate vaccine against hospitalization for community-acquired pneumonia in older US adults: a test-negative design. Clin Infect Dis. In press. doi:10.1093/cid/ciy312.