Cost-effectiveness and impact on infections and associated antimicrobial resistance of 20-valent pneumococcal conjugate vaccine in US children previously immunized with PCV13.

AIM: The US Food and Drug Administration approved the 20-valent pneumococcal conjugate vaccine (PCV20) to prevent pneumococcal disease. In the context of routine PCV20 vaccination, we evaluated the cost-effectiveness and public health and economic impact of a PCV20 catch-up program and estimated the number of antibiotic prescriptions and antibiotic-resistant infections averted. MATERIALS AND METHODS: A population-based, multi-cohort, decision-analytic Markov model was developed using parameters consistent with previous PCV20 cost-effectiveness analyses. In the intervention arm, children aged 14-59 months who previously completed PCV13 vaccination received a supplemental dose of PCV20. In the comparator arm, no catch-up PCV20 dose was given. The direct and indirect benefits of vaccination were captured over a 10-year time horizon. RESULTS: A PCV20 catch-up program would prevent 5,469 invasive pneumococcal disease cases, 50,286 hospitalized pneumonia cases, 218,240 outpatient pneumonia cases, 582,302 otitis media cases, and 1,800 deaths, representing a net gain of 30,014 life years and 55,583 quality-adjusted life years. Furthermore, 720,938 antibiotic prescriptions and 256,889 antibiotic-resistant infections would be averted. A catch-up program would result in cost savings of $800 million. These results were robust to sensitivity and scenario analyses. CONCLUSIONS: A PCV20 catch-up program could prevent pneumococcal infections, antibiotic prescriptions, and antimicrobial-resistant infections and would be cost-saving in the US.

Cost-Effectiveness of 20-Valent Pneumococcal Conjugate Vaccine Among US Children with Underlying Medical Conditions.

INTRODUCTION: A 20-valent pneumococcal conjugate vaccine (PCV20) was recently recommended for use among US children. We evaluated the cost-effectiveness of PCV20 among children aged 6 years with chronic medical conditions (CMC+) and children aged 6 years with immunocompromising conditions (IC) versus one and two doses of 23-valent pneumococcal polysaccharide vaccine (PPSV23), respectively. METHODS: A probabilistic model was employed to depict 10-year risk of clinical outcomes and economic costs of pneumococcal disease, reduction in life years from premature death, and expected impact of vaccination among one cohort of children with CMC+ and IC aged 6 years. Vaccine uptake was assumed to be 20% for both PCV20 and PPSV23. Cost per quality-adjusted life year (QALY) gained was evaluated from the US societal and healthcare system perspectives; deterministic and probabilistic sensitivity analyses (DSA/PSA) were also conducted. RESULTS: Among the 226,817 children with CMC+ aged 6 years in the US, use of PCV20 (in lieu of PPSV23) was projected to reduce the number cases of pneumococcal disease by 5203 cases, medical costs by US$8.7 million, and nonmedical costs by US$6.2 million. PCV20 was the dominant strategy versus PPSV23 from both the healthcare and societal perspectives. In the PSA, 99.9% of the 1000 simulations yielded a finding of dominance for PCV20. Findings in analyses of children with IC aged 6 years in the USA were comparable (i.e., PCV20 was the dominant vaccination strategy). Scenario analyses showed that increasing PCV20 uptake to 100% could potentially prevent > 22,000 additional cases of pneumococcal disease and further reduce medical and nonmedical costs by US$70.0 million among children with CMC+ and IC. CONCLUSIONS: Use of PCV20 among young children with CMC+ and IC in the USA would reduce the clinical burden of pneumococcal disease and yield overall cost savings from both the US healthcare system and societal perspectives. Higher PCV20 uptake could further reduce the number of pneumococcal disease cases in this population.

Cost-effectiveness of 20-valent pneumococcal conjugate vaccine in US infants.

BACKGROUND: As of June 2023, two pneumococcal conjugate vaccines, 20- (PCV20) and 15- (PCV15) valent formulations, are recommended for US infants under a 3 + 1 schedule. This study evaluated the health and economic impact of vaccinating US infants with a new expanded valency PCV20 formulation. METHODS: A population-based, multi cohort, decision-analytic Markov model was developed to estimate the public health impact and cost-effectiveness of PCV20 from both societal and healthcare system perspectives over 10 years. Epidemiological data were based on published studies and unpublished Active Bacterial Core Surveillance System (ABCs) data. Vaccine effectiveness was based on PCV13 effectiveness and PCV7 efficacy studies. Indirect impact was based on observational studies. Costs and disutilities were based on published data. PCV20 was compared to both PCV13 and PCV15 in separate scenarios. RESULTS: Replacing PCV13 with PCV20 in infants has the potential to avert over 55,000 invasive pneumococcal disease (IPD) cases, 2.5 million pneumonia cases, 5.4 million otitis media (OM) cases, and 19,000 deaths across all ages over a 10-year time horizon, corresponding to net gains of 515,000 life years and 271,000 QALYs. Acquisition costs of PCV20 were offset by monetary savings from averted cases resulting in net savings of $20.6 billion. The same trend was observed when comparing PCV20 versus PCV15, with a net gain of 146,000 QALYs and $9.9 billion in net savings. A large proportion of the avoided costs and cases were attributable to indirect effects in unvaccinated adults and elderly. From a health-care perspective, PCV20 was also the dominant strategy compared to both PCV13 and PCV15. CONCLUSIONS: Infant vaccination with PCV20 is estimated to further reduce pneumococcal disease and associated healthcare system and societal costs compared to both PCV13 and PCV15.

Serum bactericidal activity against circulating and reference strains of meningococcal serogroup B in the United States: A review of the strain coverage of meningococcal serogroup B (MenB) vaccines in adolescents and young adults.

Invasive meningococcal disease (IMD) is rare but associated with high morbidity and mortality. In the United States, the most vulnerable age groups are infants and adolescents/young adults, and the most common type of IMD is caused by serogroup B (MenB). MenB is preventable among adolescents and young adults with the use of two licensed vaccines, MenB-FHbp (Trumenba®, bivalent rLP2086; Pfizer Inc, Collegeville, PA) and MenB-4C (Bexsero®; GSK Vaccines, Srl, Italy). Because the effectiveness of MenB vaccination is dependent on broad vaccine coverage across circulating disease-causing strains, we reviewed the available clinical and real-world evidence regarding breadth of coverage of the two licensed vaccines in adolescents and young adults in the United States. Both vaccines protect against various MenB strains. More controlled data regarding breadth of coverage across MenB strains are available for MenB-FHbp compared with MenB-4C, whereas more observational data regarding US outbreak strain susceptibility are available for MenB-4C.

Two-week comparison study of olopatadine hydrochloride nasal spray 0.6% versus azelastine hydrochloride nasal spray 0.1% in patients with vasomotor rhinitis.

Olopatadine hydrochloride nasal spray 0.6% (OLO) and azelastine nasal spray 137 micrograms (AZE) are effective in treating allergic rhinitis and AZE is indicated for nonallergic vasomotor rhinitis (VMR). This study evaluates the relative safety and efficacy of OLO and AZE in patients with VMR. This randomized, double-blind, parallel-group, multicenter study compared OLO (an investigational use) with AZE over 14 days in patients (n = 129) ≥12 years of age with chronic VMR. Efficacy included the severity of nasal symptom scores. Safety included adverse events (AEs) and nasal examinations. Patient perceptions of treatment satisfaction and changes in allergy condition were determined using the Treatment Satisfaction Questionnaire for Medication and Patient Global Assessment scores. In the OLO and AZE groups, reflective scores for individual nasal symptoms (nasal congestion, rhinorrhea, postnasal drip, and sneezing) and total nasal VMR symptom scores decreased significantly from baseline to day 14 (p < 0.05). No significant between-group differences were observed (p > 0.05). No serious AEs were reported in either group. Overall, 22 and 20 AEs were reported in the OLO and AZE groups, respectively. The most common AE was taste disturbance, reported by three (5.3%) and six (10.3%) patients in the OLO and AZE groups, respectively. Patients in both groups reported similar treatment satisfaction scores and a majority of patients in both groups perceived an overall improvement in their rhinitis condition. OLO has a similar efficacy and safety profile to AZE for the management of VMR in patients ≥12 years of age.

Inhalation developmental neurotoxicity study of ethylbenzene in Crl-CD rats.

BACKGROUND: This study was conducted to evaluate the potential adverse effects of whole-body inhalation exposure of F0 and F1 parental animals from a 2-generation reproduction study of ethylbenzene on nervous system functional and/or morphologic end points in the F2 offspring from four groups of male and female Crl:CD (SD)IGS BR rats. METHODS: Thirty rats/sex/group for F0 and 25/sex/group for F1 were exposed to 0, 25, 100, and 500 ppm ethylbenzene for six hours daily for at least 70 consecutive days prior to mating for the F0 and F1 generations. Inhalation exposure for the F0 and F1 females continued throughout mating and gestation through Gestation Day (GD) 20. On lactation days (LD) 1-4, the F0 and F1 females received no inhalation exposure, but instead were administered ethylbenzene in corn oil via oral gavage at dosages estimated to result in similar internal maternal exposure based upon PBPK modeling estimates (0, 26, 90, and 342 mg/kg/day, respectively, divided into three equal doses, approximately two hours apart). Inhalation exposure of the F0 and F1 females was reinitiated on LD 5 and continued through weaning on postnatal day (PND) 21. Survival, body weights, and physical landmarks were assessed in selected F2 offspring. Neurobehavioral development of one F2-generation treatment derived offspring/sex/litter was assessed in a functional observational battery (FOB; PND 4, 11, 22, 45, and 60), motor activity sessions (PND 13, 17, 21, and 61), acoustic startle testing (PND 20 and 60), a Biel water maze learning and memory task (initiated on PND 26 or 62), and in evaluations of whole-brain measurements and brain morphometric and histologic assessments (PND 21 and 72). RESULTS: There were no adverse effects on reproductive performance in either the F0 or F1 parental generations exposed to up to 500 ppm ethylbenzene [Faber et al. Birth Defects Res Part B 77:10-21, 2006]. In the current developmental neurotoxicity component, parental ethylbenzene exposure did not adversely affect offspring survival, clinical condition, body weight parameters, or acquisition of developmental landmarks of the F2-generation treatment derived offspring. There were no alterations in FOB parameters, motor activity counts, acoustic startle endpoints, or Biel water maze performance in offspring attributed to parental ethylbenzene exposure. A few isolated instances of statistically significant differences obtained in the treatment-derived groups occurred sporadically, and were attributed to unusual patterns of development and/or behavior in the concurrent control group. There were no exposure-related differences in any neuropathology parameters in the F2-generation treatment derived offspring. CONCLUSIONS: The no observed adverse effect level (NOAEL) for maternal reproductive toxicity, developmental toxicity, and developmental neurotoxicity in this study was considered to be 500 ppm/342 mg/kg/day ethylbenzene, the highest exposure level tested in the study.

Two generation reproduction study of ethylbenzene by inhalation in Crl-CD rats.

BACKGROUND: This study was conducted to evaluate the potential adverse effects of ethylbenzene (EB) on reproductive capability from whole-body inhalation exposure of F0 and F1 parental animals. METHODS: Four groups of Crl:CD(SD)IGS BR rats (30/sex/group for F0 and 25/sex/group for F1) were exposed to 0, 25, 100, and 500 ppm EB for 6 hr/day for at least 70 consecutive days before mating. Inhalation exposure for the F0 and F1 females continued throughout mating, gestation through gestation day (GD) 20, and lactation days (LD) 5-21. On LD 1-4, females received EB in corn oil via oral gavage at dose levels of 26, 90, and 342 mg/kg/day (divided into three equal doses, approximately 2 hr apart), as calculated from a physiologically-based pharmacokinetic (PBPK) model to provide similar maternal blood area-under-concentration (AUC) as provided by inhalation. Pups were weaned on postnatal day (PND) 21 and exposure of the F1 generation started on PND 22. Estimates of internal exposure were determined by measuring EB concentrations in blood collected from F1 dams (4/group) and their culled pups 1 hr after the last gavage dose on PND 4. On PND 22, blood was collected from these same F1 dams and their weanlings for EB analysis 1 hr after a 6-hr inhalation exposure. The remainder of the F2 generation was not directly exposed. RESULTS: EB exposure did not affect survival or clinical observations. Male rats in the 500 ppm group in both generations gained weight more slowly than the controls. There were no indications of adverse effects on reproductive performance in either generation. Male and female mating and fertility indices, pre-coital intervals, spermatogenic endpoints, ovarian follicle counts, reproductive organ weights, lengths of estrous cycle and gestation, live litter size, pup weights, developmental landmarks, and postnatal survival were unaffected. No adverse exposure-related macroscopic pathology was noted at any level. CONCLUSIONS: Increased liver weights were found in the animals exposed to 500 ppm. F1 maternal whole blood EB concentrations of 0.49, 3.51, or 18.28 mg/L were found 1 hr after administration of a composite oral dose of 26, 90, or 342 mg/kg/day, respectively, but no detectable EB was found in blood samples of their F2 PND 4 culled pups. F1 maternal mean whole blood EB levels 1 hr after a 6-hr inhalation exposure on postpartum day (PPD) 22 was 0.11 mg/L (25 ppm), 0.56 mg/L (100 ppm), and 11 mg/L (500 ppm). For the offspring exposed with their dams on PND 22, F2 pup blood EB concentrations ranged from 0.017-0.039 mg/L (25 ppm), 0.165-0.465 mg/L (100 ppm), and 8.82-15.74 mg/L (500 ppm). Because decreased weight gain in the 500 ppm males was transient and no histopathological changes were associated with the increased liver weights in the 500 ppm male and female groups, these changes were not considered adverse. Therefore, for parental systemic toxicity, 100 ppm was considered a NOEL and 500 ppm a NOAEL in this study. The 500 ppm exposure concentration was considered a NOAEL for F0 and F1 reproductive toxicity and offspring developmental endpoints.