Philip O. Buck

Waning protection following 5 doses of a 3-component diphtheria, tetanus, and acellular pertussis vaccine

BACKGROUND The effectiveness of diphtheria, tetanus, and acellular pertussis (DTaP) vaccines wanes substantially after the 5th dose given at ages 4-6years, but has not been described following 5 doses of the same type of DTaP vaccine. We investigated waning effectiveness against pertussis in California over nearly 10years, which included large pertussis outbreaks, following 5 doses of GSK DTaP vaccines (DTaP3). METHODS We conducted a case-control study (NCT02447978) of children who received 5 doses of DTaP at Kaiser Permanente Northern California from 01/2006 through 03/2015. We compared time since the 5th dose in confirmed pertussis polymerase chain reaction (PCR)-positive cases with pertussis PCR-negative controls. We used logistic regression adjusted for calendar time, age, sex, race, and service area to estimate the effect of time since the 5th DTaP dose on the odds of pertussis. Our primary analysis evaluated waning after 5 doses of DTaP3. We also examined waning after 5 doses of any type of DTaP vaccines. RESULTS Our primary analysis compared 340 pertussis cases diagnosed at ages 4-12years with 3841 controls. The any DTaP analysis compared 462 pertussis cases with 5649 controls. The majority of all DTaP doses in the study population were DTaP3 (86.8%). Children who were more remote from their 5th dose were less protected than were children whose 5th dose was more recent; the adjusted odds of pertussis increased by 1.27 per year (95% CI 1.10, 1.46) after 5 doses of DTaP3 and by 1.30 per year (95% CI 1.15, 1.46) after any 5 DTaP vaccines doses. CONCLUSIONS Waning protection after DTaP3 was similar to that following 5 doses of any type of DTaP vaccines. This finding is not unexpected as most of the DTaP vaccines administered were DTaP3. Following 5 doses of DTaP3 vaccines, protection from pertussis waned 27% per year on average. NCT number: NCT02447978.

A review of the value of quadrivalent influenza vaccines and their potential contribution to influenza control

ABSTRACT The contribution of influenza B to the seasonal influenza burden varies from year-to-year. Although 2 antigenically distinct influenza B virus lineages have co-circulated since 2001, trivalent influenza vaccines (TIVs) contain antigens from only one influenza B virus. B-mismatch or co-circulation of both B lineages results in increased morbidity and mortality attributable to the B lineage absent from the vaccine. Quadrivalent vaccines (QIVs) contain both influenza B lineages. We reviewed currently licensed QIVs and their value by focusing on the preventable disease burden. Modeling studies support that QIVs are expected to prevent more influenza cases, hospitalisations and deaths than TIVs, although estimates of the case numbers prevented vary according to local specificities. The value of QIVs is demonstrated by their capacity to broaden the immune response and reduce the likelihood of a B-mismatched season. Some health authorities have preferentially recommended QIVs over TIVs in their influenza prevention programmes.

Cost-effectiveness of an Adjuvanted Recombinant Zoster Vaccine in older adults in the United States

In the United States, herpes zoster (HZ) and related complications are estimated to result in approximately

Age-appropriate compliance and completion of up to five doses of pertussis vaccine in US children

1.3 billion in medical care costs and

Assessment of the Potential Herpes Zoster and Post Herpetic Neuralgia Case Avoidance with Vaccination in the United States

1.7 billion in indirect costs annually. In this study, we compared the cost-effectiveness of a new Adjuvanted Recombinant Zoster Vaccine (RZV), containing recombinant varicella-zoster virus glycoprotein E and the AS01B Adjuvant System, versus No Vaccine, as well as versus the live attenuated HZ vaccine (Zoster Vaccine Live (ZVL)) in subjects aged 60+ years of age (YOA) and other age cohorts aged 50+ YOA. A multi-cohort Markov model was developed which follows 1 million individuals over their remaining lifetimes from the year of vaccination with annual cycle lengths. Second dose compliance for RZV was assumed to be 69%. Efficacy and waning parameters were derived from clinical trials for both vaccines. Epidemiological parameters, costs and utility model inputs were derived from US-specific population-based data. Costs and outcomes were discounted at 3% per year. Deterministic and probabilistic sensitivity analysis, along with scenario and threshold analysis were carried out to explore the overall uncertainty in the model. The model estimated that, compared to No Vaccine against HZ, RZV would prevent 103,603 HZ cases, 11,197 postherpetic neuralgia (PHN) cases, and 14,455 other complications, at an incremental cost of

National survey of pharmacy-based immunization services

11,863 per quality-adjusted life-year saved from a societal perspective. Compared to ZVL, the model estimated that, RZV would prevent 71,638 additional HZ cases, 6403 PHN cases, and over 10,582 other complications, resulting in net total societal cost savings of over

A Retrospective Cohort Study of the Incidence, Health Care Resource Utilization and Costs of International Classification of Diseases, Clinical Modification, 9th Revision Diagnosed Influenza and Related Complications in US Children

96 million. The results were robust to a wide range of sensitivity analyses. Vaccination against HZ with RZV is cost-effective compared to No Vaccine and cost-saving compared to ZVL, in the US population aged 60+ YOA. Clinicaltrial.gov. registered#: NA.

Health Outcomes Associated with Mild versus Moderate-to-Severe Laboratory-Confirmed Influenza in 6- to 35-month-old Children

ABSTRACT Background: In the United States (US), diphtheria, tetanus, and acellular pertussis (DTaP) vaccination is recommended at 2, 4, and 6 months (doses 1–3), 15–18 months (dose 4), and 4–6 years (dose 5). The objective of this study (GSK study identifier: HO-14–14383) was to examine DTaP completion and compliance rates among commercially insured and Medicaid-enrolled children. Secondarily, the study aimed at identifying predictors of compliance/completion. Methods: Truven Health MarketScan Commercial and Multi-State Medicaid databases (2005–2013) were analyzed separately. Children born during 2005–2011 with ≥ 2 years continuous enrollment from birth provided data for doses 1–4; those with continuous enrollment from birth to their seventh birthday provided dose 5 data. Series compliance (each recommended dose by 3, 5, and 7 months; 19 months; seventh birthday) and completion (3 doses by 8 months; 4 by 24 months; 5 by seventh birthday) were calculated. Predictors of compliance/completion were identified using multivariable logistic regression. Results: A total of 367,493 commercially insured and 766,153 Medicaid-enrolled children were followed for ≥ 2 years; and 23,574 and 41,284, respectively, for ≥ 7 years. Series compliance to doses 1–3, 1–4, and 1–5 were 67.2%, 55.3%, 47.5% (commercial) and 37.4%, 27.3%, 14.4% (Medicaid), respectively. Predictors of better compliance/completion included: later birth year (commercial/Medicaid) and higher household income (commercial); predictors of worse compliance/completion included: Northeast residence (commercial), birth hospitalization ≥ 14 days (commercial/Medicaid), and Black race/ethnicity (Medicaid). Conclusions: DTaP series compliance/completion improved over time, but appear to be suboptimal. As this could increase pertussis risk, greater awareness of the importance of timely vaccination completion is needed. GSK study identifier: HO-14–14383

Cost-effectiveness of candidate adjuvanted subunit vaccine for vaccinating U.S. adults not previously vaccinated against herpes zoster:

Abstract Background Herpes zoster (HZ), commonly referred to as shingles, is a reactivation of latent varicella zoster virus in patients previously infected. Clinical characteristics of HZ include painful rash with potential complications, including post herpetic neuralgia (PHN). Care for HZ and PHN incurs significant costs and vaccination is beneficial. The aim of this study was to compare the impact on HZ and PHN case avoidance of two HZ vaccines, an available live-attenuated zoster vaccine (zoster vaccine live [ZVL]) vs. a candidate non-live adjuvanted HZ subunit vaccine (HZ/su), in the US population. Methods A Markov model called ZONA (ZOster ecoNomic Analyses) was developed following two age cohorts (≥60 years to represent the current ACIP recommendation and ≥65 years to represent the Medicare population) over their lifetimes from the year of vaccination. Demographic data were obtained from the US Census, whereas HZ incidence and the proportion of HZ individuals developing PHN were derived from published US-specific sources. Age-specific vaccine efficacy and waning rates were based on published clinical trial data. Vaccine coverage for both vaccines was assumed to be 30.6% and 34.2% in the two age cohorts, respectively, based on CDC data; compliance of the second dose of the HZ/su vaccine was 69%, based on data from clinical trials and Hepatitis B seconddose completion. Sensitivity analyses demonstrated robustness of the base analysis findings. Results In the US, for cohorts of 66.83 million (M) persons aged 60+ and 47.76M aged 65+ it was estimated that the HZ/su vaccine would reduce the number of HZ cases by 2.12M and 1.55M in the two age cohorts, respectively, compared with 0.65M and 0.45M using the ZVL. Furthermore, the HZ/su vaccine would reduce the number of PHN cases by 0.23M and 0.18M in the two age cohorts, respectively, compared with 0.10M and 0.09 using the ZVL. The number needed to vaccinate to prevent one HZ case were 10 and 11, in the respective cohorts, using the HZ/su vaccine compared with 31 and 37, in the respective cohorts, using the ZVL. Conclusion Due to higher and sustained vaccine efficacy, the candidate HZ/su vaccine demonstrated superior public health impact in the US compared with the currently available ZVL. Disclosures B. J. Patterson, GSK: Employee and Shareholder, GSK stock options or restricted shares and Salary; Pennsylvania Pharmacists Association: Scientific Advisor, stipend; P. O. Buck, GSK: Employee and Shareholder, GSK stock options or restricted shares and Salary; J. Carrico, RTI Health Solutions: Employee, Salary GSK: Research Contractor, Research support; K. A. Hicks, RTI: Employee, Salary GSK: Research Contractor, Research support; D. Curran, GSK: Employee and Shareholder, GSK stock options or restricted shares and Salary; D. Van Oorschot, GSK: Employee, Salary; J. E. Pawlowski, GSK: Employee and Shareholder, GSK stock options or restricted shares and Salary; B. Y. Lee, GSK: Consultant, Consulting fee; B. P. Yawn, GSK: Consultant and Scientific Advisor, Consulting fee