Assessing the long-term implications of age 9 initiation of HPV vaccination on series completion by age 13-15 in the US: projections from an age-structured vaccination model.

Introduction: Routine human papillomavirus (HPV) vaccination in the US is recommended at ages 11 or 12 years and can be given at age 9. Vaccination completion rates among adolescents 13-15 years in the US remain below the 80% goal. This study evaluated the long-term effects of increasing proactive HPV vaccination initiation rates at age 9 years in completion rates of adolescents. Methods: An age-structured vaccination model was developed and parametrized based on the National Immunization Survey-Teen (NIS-Teen) survey data. The model projected vaccination coverage (by vaccination status and age group), for 20 years, for a routine initiation scenario (no increase in initiation rates of 9-year-olds) and different proactive initiation (increased age 9 initiation) scenarios. The time to reach a completion rate of 80% for 13-15-year-olds was estimated. The model also generated projections stratified for subgroups of interest. Results: Results indicated that vaccine completion rates of 80% in 13-15-year-olds may not be achieved by 2040 under current trends of routine initiation at ages 11 or 12 years. However, increasing initiation rates in 9-year-olds by 1% and 3% annually could shorten the time to achieve 80% completion by 4 and 8 years, respectively. Stratification analyses showed that increasing initiation rates in 9-year-olds can also reduce disparities across subgroups in the time to achieve vaccination completion targets. Discussion: Increasing HPV vaccination initiation rates in 9-year-olds by as little as 1%-3% annually may be an effective strategy to improve HPV vaccination completion rates in adolescents by age 15 and reach the Healthy People goal of 80% completion much earlier.

Structured Literature Review to Identify Human Papillomavirus's Natural History Parameters for Dynamic Population Models of Vaccine Impacts.

Human papillomavirus (HPV) is a common sexually transmitted virus that can cause cervical cancer and other diseases. Dynamic transmission models (DTMs) have been developed to evaluate the health and economic impacts of HPV vaccination. These models typically include many parameters, such as natural history of the disease, transmission, demographic, behavioral, and screening. To ensure the accuracy of DTM projections, it is important to parameterize them with the best available evidence. This study aimed to identify and synthesize data needed to parametrize DTMs on the natural history of HPV infection and related diseases. Parameters describing data of interest were grouped by their anatomical location (genital warts, recurrent respiratory papillomatosis, and cervical, anal, vaginal, vulvar, head and neck, and penile cancers), and natural history (progression, regression, death, cure, recurrence, detection), and were identified through a systematic literature review (SLR) and complementary targeted literature reviews (TLRs). The extracted data were then synthesized by pooling parameter values across publications, and summarized using the range of values across studies reporting each parameter and the median value from the most relevant study. Data were extracted and synthesized from 223 studies identified in the SLR and TLRs. Parameters frequently reported pertained to cervical cancer outcomes, while data for other anatomical locations were less available. The synthesis of the data provides a large volume of parameter values to inform HPV DTMs, such as annual progression rates from cervical intraepithelial neoplasia (CIN) 1 to CIN 2+ (median of highest quality estimate 0.0836), CIN 2 to CIN 3+ (0.0418), carcinoma in situ (CIS) 2 to local cancer+ (0.0396), and regional to distant cancer (0.0474). Our findings suggest that while there is a large body of evidence on cervical cancer, parameter values featured substantial heterogeneity across studies, and further studies are needed to better parametrize the non-cervical components of HPV DTMs.

Comparative Effectiveness of Pegcetacoplan Versus Ravulizumab and Eculizumab in Complement Inhibitor-Naïve Patients with Paroxysmal Nocturnal Hemoglobinuria: A Matching-Adjusted Indirect Comparison.

INTRODUCTION: In the absence of head-to-head trials, this study compared treatment outcomes with the C3 complement inhibitor pegcetacoplan versus the C5 complement inhibitor eculizumab or ravulizumab in complement inhibitor-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH). METHODS: A matching-adjusted indirect comparison was conducted using individual patient data from the pegcetacoplan arm of the PRINCE trial (NCT04085601; n = 34) and aggregate data from the ravulizumab (n = 125) and eculizumab (n = 121) arms of the ALXN1210-PNH-301 trial (NCT03056040). Clinical and quality of life endpoints were evaluated after matching patients in the two trials on baseline characteristics. The weighted Wald test with 95% confidence interval was used to compare categorical and continuous variables (i.e., weighted chi-squared and z tests, respectively). Bias factor analysis was performed to quantify the extent of residual bias from unmeasured confounders. RESULTS: After weighting, treatment with pegcetacoplan was associated with statistically significant improvements in most clinical endpoints compared with ravulizumab or eculizumab treatment. These included: greater absolute and percent reductions in lactate dehydrogenase (LDH) level and increase in hemoglobin level from baseline; shorter time to first occurrence of LDH normalization; larger proportions of patients achieving hemoglobin stabilization and avoiding transfusion, with fewer packed red blood cell units transfused; and a smaller proportion of patients experiencing breakthrough hemolysis (all p < 0.05). Patients receiving pegcetacoplan also had a greater increase in general health status score from baseline compared with those receiving C5 complement inhibitors. CONCLUSION: Pegcetacoplan provides clinical benefits as first-line treatment for complement inhibitor-naïve patients with PNH. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04085601.