Shannon Allen Ferrante

Sustained efficacy of the pentavalent rotavirus vaccine, RV5, up to 3.1 years following the last dose of vaccine.

Background: Rotavirus gastroenteritis (RVGE) is a common cause of childhood hospitalizations and emergency department (ED) visits. In the Rotavirus Efficacy and Safety Trial (REST), the pentavalent rotavirus vaccine (RV5) significantly reduced RVGE-associated hospitalizations and ED visits for up to 2 years following the last vaccine dose. This study evaluated whether RV5 remained efficacious beyond 2 years. Methods: A total of 20,736 infants from Finland, initially in REST, were followed for RVGE-associated hospitalizations and ED visits in a Finnish extension study (FES) for up to 3.1 years after vaccination (age, ∼3.5 years). Results: The FES added >18,500 person-years and captured 150 RVGE-associated hospitalizations and ED visits (11 RV5; 139 placebo). In REST + FES, RV5 reduced RVGE-associated hospitalizations and ED visits, regardless of rotavirus serotype, by 94.0% (95% confidence interval [CI]: 91.4%–95.9%) for up to 3.1 years after vaccination. RV5 also conferred significant protection against hospitalizations and ED visits associated with rotavirus serotypes G1 (95.5%; 95% CI: 92.8%–97.2%), G2 (81.9%; 95% CI: 16.1%–98.0%), G3 (89.0%; 95% CI: 53.3%–98.7%), G4 (83.4%; 95% CI: 51.2%–95.8%), and G9 (94.2%; 95% CI: 62.2%–99.9%). Rate reductions (95% CI) in hospitalizations and ED visits during the first, second, and third years of life were 94.0% (90.0%–96.5%), 94.7% (90.7%–97.2%), and 85.9% (51.6%–97.2%), respectively. Conclusions: RVGE-associated hospitalizations and ED visits remain common in the second year of life but decrease in the third year of life. RV5 showed sustained protective efficacy against RVGE-associated hospitalizations and ED visits, regardless of rotavirus serotype, for up to 3.1 years after vaccination.

Cost-effectiveness of boceprevir in patients previously treated for chronic hepatitis C genotype 1 infection in the United States.

OBJECTIVES The phase 3 trial, Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol-2 (RESPOND-2), demonstrated that the addition of boceprevir (BOC) to peginterferon-ribavirin (PR) resulted in significantly higher rates of sustained virologic response (SVR) in previously treated patients with chronic hepatitis C virus (HCV) genotype-1 infection as compared with PR alone. We evaluated the cost-effectiveness of treatment with BOC in previously treated patients with chronic hepatitis C in the United States using treatment-related data from RESPOND-2 and PROVIDE studies. METHODS We developed a Markov cohort model to project the burden of HCV disease, lifetime costs, and quality-adjusted life-years associated with PR and two BOC-based therapies-response-guided therapy (BOC/RGT) and fixed-duration therapy for 48 weeks (BOC/PR48). We estimated treatment-related inputs (efficacy, adverse events, and discontinuations) from clinical trials and obtained disease progression rates, costs, and quality-of-life data from published studies. We estimated the incremental cost-effectiveness ratio (ICER) for BOC-based regimens as studied in RESPOND-2, as well as by patients prior response to treatment and the IL-28B genotype. RESULTS BOC-based regimens were projected to reduce the lifetime incidence of liver-related complications by 43% to 53% in comparison with treatment with PR. The ICER of BOC/RGT in comparison with that of PR was

Lower risk of hypoglycemia with sitagliptin compared to glipizide when either is added to metformin therapy: a pre-specified analysis adjusting for the most recently measured HbA1c value

30,200, and the ICER of BOC/PR48 in comparison with that of BOC/RGT was

Cost-effectiveness of boceprevir co-administration versus pegylated interferon-α2b and ribavirin only for patients with hepatitis C genotype 1 in Singapore.

91,500. At a willingness-to-pay threshold of

Boceprevir for Chronic Genotype 1 Hepatitis C Virus in the Current Health Care Setting in Greece: A Cost-effectiveness Analysis.

50,000, the probabilities of BOC/RGT and BOC/PR48 being the preferred option were 0.74 and 0.25, respectively. CONCLUSIONS In patients previously treated for chronic HCV genotype-1 infection, BOC was projected to increase quality-adjusted life-years and reduce the lifetime incidence of liver complications. In addition, BOC-based therapies were projected to be cost-effective in comparison with PR alone at commonly used willingness-to-pay thresholds.

Pembrolizumab versus the standard of care for relapsed and refractory classical Hodgkin’s lymphoma progressing after brentuximab vedotin: an indirect treatment comparison

Abstract Background: In a previously-published study, adding sitagliptin or glipizide to ongoing metformin therapy provided similar HbA1c improvement (both groups, −0.7%) after 52 weeks in patients with type 2 diabetes (T2DM). Significantly fewer patients experienced symptomatic hypoglycemia with sitagliptin (5% of 588 patients) compared to glipizide (32% of 584 patients). Glycemic efficacy and patient characteristics may influence hypoglycemic events. The present analysis evaluated the risk of hypoglycemia with sitagliptin or glipizide after adjusting for the most recently measured HbA1c value. Methods: Data for this analysis were from the aforementioned 52-week, randomized, double-blind, active-controlled study. The primary endpoint was confirmed hypoglycemia (i.e., symptomatic hypoglycemia confirmed with a concurrent fingerstick glucose ≤70 mg/dL [3.9 mmol/L]); the secondary endpoint was severe hypoglycemia (requiring medical or non-medical assistance or symptoms of neuroglycopenia). Complementary log-log regression random effects models with terms for treatment, most recently measured HbA1c value, time (i.e., days since randomization), gender, and age (< or ≥65 years) were used to assess adjusted subject-specific treatment effects. Results: Over the full range of HbA1c levels and follow-up time, the risk of confirmed hypoglycemic events was lower with sitagliptin compared with glipizide (31 vs. 448 events; adjusted hazard ratio [HR] = 0.05 [95% CI: 0.03, 0.09], p < 0.001). The risk was also lower with sitagliptin in the younger (HR = 0.06 [95% CI: 0.03, 0.12], p < 0.001) and older (HR = 0.02 [0.01, 0.08], p < 0.001) age groups compared with glipizide. For severe hypoglycemia events (2 vs. 22), the risk was lower with sitagliptin (HR = 0.08 [95% CI: 0.01, 0.47]; p = 0.005). Limitations: The actual time between the HbA1c measurement and the hypoglycemic event was variable and not controlled for in the analysis. Conclusion: In pre-specified analyses adjusting for the most recently measured HbA1c value, there was a substantial reduction in risk for confirmed hypoglycemia with sitagliptin compared to glipizide when added to ongoing metformin therapy in patients with T2DM. The risk of confirmed hypoglycemia was very low in younger and older patients treated with sitagliptin.

Efficacy of the pentavalent rotavirus vaccine, RotaTeq®, in Finnish infants up to 3 years of age: the Finnish Extension Study.

BACKGROUND Patients infected with chronic HCV genotype 1 experience liver complications as the disease progresses. This study aims to project the long-term reduction of liver complications and cost-effectiveness of treatment strategies, including co-administrating boceprevir (BOC) with pegylated interferon-α2b (PEG-IFN) and ribavirin compared with standard of care (SOC) of PEG-IFN and ribavirin only. METHODS A Markov model was created to estimate the expected costs and quality-adjusted life-years (QALYs) associated with treatment strategies outlined in the BOC package insert in Singapore. Patient characteristics were from pivotal trials, the transition probabilities and QALYs were estimated from publications, and the pharmaceutical and health status costs were obtained from a public hospital in Singapore. The threshold of cost-effectiveness was chosen as 65,000 SGD for this study. RESULTS For treatment-naive patients, BOC is highly cost-effective compared with SOC (179 SGD/QALY) and cost-saving for patients who have failed prior treatment, due to higher QALYs from better sustained virological response (SVR) and lower costs from avoidance of complications. Sub-group analyses show that BOC is cost-effective for non-cirrhotic treatment-experienced patients and null responders. It out-performs SOC for treatment-naive non-cirrhotic and cirrhotic patients who have failed prior treatment. Even after adjusting for higher prevalence of favourable IL28B genotype in Asians, BOC is cost-effective compared with SOC. Only untreated cirrhotic patients showed inconclusive cost-effectiveness for BOC. CONCLUSIONS Compared with SOC, BOC prevents more HCV liver complications from HCV genotype 1, particularly in patients who have failed previous SOC. Improved SVR and shortened duration of treatment result in BOC being potentially cost-saving or cost-effective in an Asian population.

Boceprevir for previously untreated patients with chronic hepatitis C Genotype 1 infection: a US-based cost-effectiveness modeling study

PURPOSE Boceprevir, as an add-on to the standard of care (SOC) for chronic genotype 1 hepatitis C virus (G1 HCV), pegylated interferon + ribavirin for 48 weeks (PEG + RBV), has been reported to have a clinical profile superior to that of SOC alone. The objective of the present study was to compare the cost-effectiveness of triple therapy with PEG + RBV + boceprevir to that of SOC in treatment-naive and treatment-experienced patients with G1 HCV in Greece. METHODS A Markov model that simulated the quality-adjusted life expectancy and corresponding costs of treating G1 HCV infection provided the basis of the analysis. Treatment strategies under consideration were those in the Phase III boceprevir trials: (1) boceprevir response-guided therapy (shortened treatment duration for early responders); (2) fixed-duration (4-week) SOC plus 44 weeks of triple therapy; and (3) 48-week SOC. Efficacy data and the baseline characteristics of the study population were based on data from the SPRINT-2 (Serine Protease Inhibitor Therapy 2) and RESPOND-2 (Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2) clinical trials. Health care resource utilization and costs reflect the local clinical setting, with a 3% discount per annum, and were assessed from a third-party payer perspective. FINDINGS Triple therapy was projected to reduce liver complications (eg, decompensated cirrhosis, hepatocellular carcinoma, need for liver transplantation, and liver-related death) by 44% to 45% and 49% to 53% in treatment-naive and treatment-experienced patients, respectively, over a lifetime horizon, leading to corresponding gains of 0.87 and 1.25 quality-adjusted life-years gained per patient. Taking into account the costs of medications, treatment, and outcomes management, the estimated incremental cost-effectiveness ratios of triple therapy versus SOC were €10,003 and €10,852 per quality-adjusted life-years gained in treatment-naïve and treatment-experienced patients. Extensive sensitivity analyses suggested that the findings were robust over a wide range of inputs. IMPLICATIONS Based on the findings from the present analysis, the addition of boceprevir to PEG + RBV for the treatment of patients with G1 HCV may be a cost-effective alternative in the health care setting in Greece.

Cost-Effectiveness Analysis of Boceprevir for the Treatment of Chronic Hepatitis C Virus Genotype 1 Infection in Portugal

ABSTRACT Background: There is significant unmet need among patients with relapsed and refractory classical Hodgkin’s lymphoma (RRcHL) who have failed multiple lines of therapy, including brentuximab vedotin (BV). Pembrolizumab, an immune checkpoint inhibitor, is one possible treatment solution for this population. Research methods: The objective of this study was to compare progression-free survival (PFS) with standard of care (SOC) versus pembrolizumab in previously BV treated RRcHL patients. A systematic literature review identified one observational study of SOC that was suitable for comparison with KEYNOTE-087, the principal trial of pembrolizumab in this population. Both naïve and population-adjusted (using outcomes regression) pairwise indirect comparisons were conducted. The primary analysis included all patients who had failed BV, with a secondary analysis conducted including only those known to have failed BV that was part of definitive treatment. Results: In the primary analysis, SOC was inferior to pembrolizumab in both the unadjusted comparison (HR 5.00 [95% confidence interval (CI) 3.56–7.01]) and the adjusted comparison (HR 6.35 [95% CI 4.04–9.98]). These HRs increased to 5.16 (95% CI 3.61–7.38) and 6.56 (95% CI 4.01–10.72), respectively, in the secondary analysis. Conclusion: Pembrolizumab offers a significant improvement in PFS compared to SOC in this population.