Costs of Severe Maternal Morbidity During Pregnancy in US Commercially Insured and Medicaid Populations: An Observational Study.

OBJECTIVE: To estimate the maternity-related cost of health care services in women with and without severe maternal morbidity (SMM). METHODS: Women with a live inpatient birth in the calendar year 2013 were identified in the MarketScan® Commercial and Medicaid health insurance claims databases. Costs were defined as the amounts paid by insurers plus out-of-pocket and third-party payments. Costs were calculated as total maternity-related costs and categorized as prenatal, delivery, and postpartum costs. SMM was identified using the CDC algorithm of 25 ICD-9 diagnostic and procedural codes. Variables associated with higher delivery costs were determined by multivariable linear regression analysis. RESULTS: A total of 750 women met the criteria for SMM in the Commercial population. The total, per-patient mean costs of care for women without and with SMM were $14,840 and $20,380, respectively. Delivery hospitalization costs were 76-77% of total mean costs for women without and with SMM. A total of 99 women met the criteria for SMM in the Medicaid population. The total, per-patient mean costs of care for women without and with SMM were $6894 and $10,134, respectively. Delivery costs were 71-72% of total costs. Variables independently predictive of increased delivery costs in both Commercial and Medicaid populations were delivery by cesarean section, multifetal gestation, gestational hypertension/preeclampsia, and obstetric infection. CONCLUSIONS: The occurrence of SMM was associated with an increase in maternity-related costs of 37% in the Commercial and 47% in the Medicaid population. Some of the factors associated with increased delivery hospitalization costs may be prevented.

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 patient's 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 $30,200, and the ICER of BOC/PR48 in comparison with that of BOC/RGT was $91,500. At a willingness-to-pay threshold of $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.

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

BACKGROUND: SPRINT-2 demonstrated that boceprevir (BOC), an oral hepatitis C virus (HCV) nonstructural 3 (NS3) protease inhibitor, added to peginterferon alfa-2b (P) and ribavirin (R) significantly increased sustained virologic response rates over PR alone in previously untreated adult patients with chronic HCV genotype 1. We estimated the long-term impact of triple therapy vs. dual therapy on the clinical burden of HCV and performed a cost-effectiveness evaluation. METHODS: A Markov model was used to estimate the incidence of liver complications, discounted costs (2010 US$), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) of three treatment strategies for treatment-naïve patients with chronic HCV genotype 1. The model simulates the treatment regimens studied in SPRINT-2 in which PR was administered for 4 weeks followed by: 1) placebo plus PR for 44 weeks (PR48); 2) BOC plus PR using response guided therapy (BOC/RGT); and 3) BOC plus PR for 44 weeks (BOC/PR48) and makes projections within and beyond the trial. HCV-related state-transition probabilities, costs, and utilities were obtained from previously published studies. All costs and QALYs were discounted at 3%. RESULTS: The model projected approximately 38% and 43% relative reductions in the lifetime incidence of liver complications in the BOC/RGT and BOC/PR48 regimens compared with PR48, respectively. Treatment with BOC/RGT is associated with an incremental cost of $10,348 and an increase of 0.62 QALYs compared to treatment with PR48. Treatment with BOC/PR48 is associated with an incremental cost of $35,727 and an increase of 0.65 QALYs compared to treatment with PR48. The ICERs were $16,792/QALY and $55,162/QALY for the boceprevir-based treatment groups compared with PR48, respectively. The ICER for BOC/PR48 compared with BOC/RGT was $807,804. CONCLUSION: The boceprevir-based regimens used in the SPRINT-2 trial were projected to substantially reduce the lifetime incidence of liver complications and increase the QALYs in treatment-naive patients with hepatitis C genotype 1. It was also demonstrated that boceprevir-based regimens offer patients the possibility of experiencing great clinical benefit with a shorter duration of therapy. Both boceprevir-based treatment strategies were projected to be cost-effective at a reasonable threshold in the US when compared to treatment with PR48.

Inconsistencies in the days supply values reported in pharmacy claims databases for biologics with long maintenance intervals.

BACKGROUND: Days supply values reported in large administrative claims databases are commonly used to estimate drug exposure and quantify adherence and persistence with prescribed therapy. In recent claims database studies assessing treatment patterns for biologic therapies, a high frequency of 28-31-days supply values has been observed for therapies with label-recommended maintenance dosing intervals longer than 4 weeks. Such inconsistencies suggest potential inaccuracy of days supply data. OBJECTIVE: To confirm the existence and describe the extent of inconsistencies in the reported days supply values and the documented fill intervals among prescription claims from administrative claims databases for 2 different biologics with label-recommended maintenance dosing intervals longer than 4 weeks and 2 biologics with intervals less than or equal to 4 weeks. METHODS: Using data from 2 large US administrative claims databases (IBM MarketScan Commercial Claims and Encounters and the Optum Clinformatics Data Mart Socio-economic Status [SES]), the reported days supply values and associated intervals between consecutive fills for 2 biologics with maintenance dosing intervals longer than 4 weeks (guselkumab and ustekinumab) and 2 with intervals less than or equal to 4 weeks (adalimumab and ixekizumab) were described. For all fill pairs with reported days supply values of 28-31 days, the percentage with inconsistent fill intervals (defined as >45 days or >60 days) was calculated. RESULTS: Across all datasets, the proportions of fill pairs with inconsistent days supply values and fill intervals (ie, days supply values of 28-31 days but fill intervals of >45 days) were 41.8%-73.4% for guselkumab, 33.4%-59.4% for ustekinumab, 8.5%-9.5% for adalimumab, and 7.3%-11.4% for ixekizumab. The same trend was observed across these biologics when using more than 60 days to define an inconsistent fill interval. Unlike adalimumab and ixekizumab, a wide distribution of fill intervals was observed among guselkumab and ustekinumab fill pairs with 28-31 days supply values, with peaks evident at approximately 28-31 days as well as around the label-recommended maintenance dosing intervals for these therapies (56 or 84 days). CONCLUSIONS: This study demonstrated a large discrepancy between days supply values and fill intervals reported in administrative claims data for biologics with label-recommended maintenance dosing intervals longer than 4 weeks (ie, guselkumab and ustekinumab), potentially suggesting widespread underestimation of days supply values for these therapies. Such inconsistencies in the reported days supply values may lead to underestimation of treatment adherence and persistence for these biologics, which could be mitigated by systematic data imputation. DISCLOSURES: This study was funded by Janssen Scientific Affairs, LLC. Ms Xu and Drs Ferrante, Fitzgerald, Pericone, and Wu are employees of Janssen Scientific Affairs, LLC, and shareholders of Johnson & Johnson, of which Janssen Scientific Affairs, LLC, is a wholly owned subsidiary. Funding for programming support and medical writing and editorial assistance was provided by Janssen.

Racial and Ethnic Disparities in Treatment Initiation Among Patients with Newly Diagnosed Psoriatic Arthritis: A Retrospective Medicaid Claims Database Study.

INTRODUCTION: In patients with psoriatic arthritis (PsA), potential differences in care by race/ethnicity have not been well studied. METHODS: This retrospective, observational cohort analysis utilized the IBM MarketScan® Multi-State Medicaid database. Patients aged ≥ 18 years with two or more PsA-related claims between January 1, 2010 and December 31, 2019, and ≥ 12 months of continuous enrollment before the first diagnosis of PsA (index date) were included. Outcomes evaluated were the use of disease-modifying antirheumatic drugs (DMARDs) overall and by type (conventional synthetic, biologic, targeted synthetic) within 12 months following initial PsA diagnosis, as well as the time to DMARD initiation after initial PsA diagnosis, stratified by race/ethnicity. Multivariate Cox proportional hazards models were used to assess potential associations between patient baseline characteristics and time to DMARD initiation. RESULTS: Among patients with newly diagnosed PsA (N = 3432), the mean age was 44.4 years, 69.9% were female, 77.4% were White, and 10.1% were Black. Of the 2993 patients with at least 12 months of follow-up, fewer Black patients received any DMARD therapy compared with White patients (68.4 vs. 76.4%, respectively, p = 0.002), and, specifically, a lower percentage of Black patients received biologic DMARDs compared with White patients (33.6 vs. 42.6%, respectively, p = 0.003). After adjusting for baseline characteristics, Black patients had significantly longer time to initiation of any DMARD (HR [95% CI] 0.82 [0.71-0.94]) and biologic DMARD (0.84 [0.71-0.99]) compared with White patients. Other baseline variables such as older age, anxiety, and hepatitis C were also significantly associated with longer time to any DMARD initiation after initial PsA diagnosis. CONCLUSIONS: Time to treatment initiation was significantly longer in Black patients compared with White patients with newly diagnosed PsA. These findings suggest care delivery disparities in patients with PsA and highlight the need for future studies to understand factors that drive the observed differences in drug therapy by race/ethnicity.

Treatment patterns and overall survival of patients with double-class and triple-class refractory multiple myeloma: a US electronic health record database study.

Patients with relapsed/refractory multiple myeloma (RRMM) resistant to multiple drug classes remain a high unmet need population. This longitudinal retrospective cohort study assessed real-world treatment patterns and outcomes in adults with RRMM. Patients who had three or more prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (double-exposed) were further categorized as refractory to a PI and an immunomodulatory agent (double-class refractory, n = 381) or additionally to an anti-CD38 monoclonal antibody (triple-class refractory, n = 173). Treatment options are limited for patients with double-class or triple-class refractory disease. Retreatment is a part of standard of care. Bortezomib and lenalidomide had the highest retreatment rates among double-class and triple-class refractory patients. Survival outcomes remain poor among RRMM patients with median overall survival (OS) of 22.3 and 11.6 months for double-class refractory and triple-class refractory patients, respectively. This study highlights the need for novel efficacious therapies in this heavily pretreated RRMM population.

Assessing the treatment pattern, health care resource utilisation, and economic burden of multiple myeloma in France using the Système National des Données de Santé (SNDS) database: a retrospective cohort study.

BACKGROUND: Real-world data on health care resource utilisation (HCRU) and costs for French patients with multiple myeloma (MM) are limited due to the quickly evolving MM treatment landscape. This retrospective, national-level study quantified the MM economic burden in France. METHODS: The study included patients with newly diagnosed MM from the Système National des Données de Santé coverage claims database between 2013 and 2018 who received active treatment within 30 days of diagnosis. HCRU included hospitalisations, drugs, consultations, procedures, tests, devices, transport, and sick leave. Costs were annualized to 2019 prices. Drug treatments, reported by line of therapy (LOT), were algorithmically defined using drug regimen, duration of therapy, and gaps between treatments. Analyses were stratified by stem cell transplantation status and LOT. RESULTS: Among 6413 eligible patients, 6229 (97.1%) received ≥ 1 identifiable LOT; most received 1 (39.8%) or 2 LOT (27.5%) during follow-up. Average annual hospitalisation was 6.3 episodes/patient/year (median duration: 11.6 days). The average annual cost/patient was €58.3 K. Key cost drivers were treatment (€28.2 K; 39.5% of total HCRU within one year of MM diagnosis) and hospitalisations (€22.2 K; 48.6% of total HCRU costs in first year). Monthly treatment-related costs increased from LOT1 (€2.447 K) and LOT5 + (€7.026 K); only 9% of patients received LOT5 + . At LOT4 + , 37 distinct regimens were identified. Hospitalisation costs were higher in patients with stem cell transplantation than total population, particularly in the first year. CONCLUSIONS: This study showed a high economic burden of MM in France (€72.37 K/patient/year in the first year) and the diversity of regimens used in late-line treatments.

Incidence of corneal adverse events in patients with multiple myeloma and their clinical and economic impact: A real-world retrospective cohort study.

AIMS: Ocular toxicities are common adverse events (AEs) associated with anticancer agents. There is a paucity of data documenting their impact on patient care. This study assessed the clinical and economic burden of corneal AEs and related symptoms (collectively termed corneal AEs) in patients receiving multiple myeloma (MM) treatment. MATERIALS AND METHODS: Adults with a newly diagnosed MM (MM cohort) were identified from PharMetrics Plus, a US insurance claims database. Incidence, outpatient (OP) care, emergency department (ED) visits, hospitalizations, and costs were assessed for corneal AEs of interest: keratopathy/keratitis, blurred vision/decreased acuity, dry eye, eye pain, and photophobia. Incidence of new corneal AEs, healthcare resource utilization (HCRU), corneal AE-related HCRU, and costs were assessed and benchmarked against a hematology cohort of patients. RESULTS: The MM cohort included 2,120 patients with a median follow-up of 734.5 days. Overall, 11.7% of patients in the MM cohort and 7.4% in the hematology cohort had ≥1 corneal AE of interest. In the MM cohort, dry eye (6.1%), blurred vision/decreased acuity (3.4%), and keratopathy/keratitis (2.5%) were the most frequent. The overall median corneal AE-related per-patient-per-month (PPPM) cost was $27, predominantly contributed by OP care (median $19 PPPM). During follow-up, 4.8% of patients visited the ED, 3.6% were hospitalized, and 42.5% of patients visited an ophthalmologist/optometrist (∼1.69 visits/year). Costs of these visits were negligible (median PPPM $19) compared to total all-cause costs (median PPPM $17,286). LIMITATIONS: The results can only be generalized to commercially insured and Medicare Advantage patients. Claims-based diagnosis of corneal AEs may underestimate true incidences. CONCLUSIONS: Corneal AEs were observed in ∼12% of patients in the MM cohort, the most common were keratopathy/keratitis, dry eye, and blurred vision. Most of them required only OP care. The clinical and economic burden for treating corneal AEs was low when compared with total all-cause or MM-related PPPM costs.

DREAMM-2: Indirect Comparisons of Belantamab Mafodotin vs. Selinexor + Dexamethasone and Standard of Care Treatments in Relapsed/Refractory Multiple Myeloma.

INTRODUCTION: Single-agent belantamab mafodotin (belamaf; BLENREP) demonstrated deep and durable responses in patients with relapsed/refractory multiple myeloma and ≥ 3 prior lines of therapy, including an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody (DREAMM-2; NCT03525678). METHODS: At the time of this study, STORM Part 2, NCT02336815 (selinexor plus low-dose dexamethasone; sel + dex) was systematically identified as the only feasible comparator to the DREAMM-2 cohort. Matching-adjusted indirect comparisons (MAIC) evaluated efficacy and safety of belamaf (2.5 mg/kg; n = 97) versus sel + dex (80 mg + 20 mg, respectively; n = 123). Populations were weighted for clinically validated effect modifiers and prognostic factors. Outcomes included overall survival (OS), progression-free survival (PFS), duration of response (DoR), overall response rate (ORR), time to response (TTR), and safety. The relative efficacy of belamaf versus standard of care (SoC) on OS was estimated by a Bucher indirect treatment comparison using the MAIC-adjusted hazard ratios (HR) for OS of belamaf (DREAMM-2) versus sel + dex (STORM Part 2) and a HR adjusted for refractoriness to carfilzomib and high-risk cytogenetics of sel + dex (STORM) versus SoC (MAMMOTH). RESULTS: Belamaf demonstrated improved OS (HR 0.53; 95% confidence interval 0.34, 0.83; p = 0.005) and DoR (0.41; 0.21, 0.83; p = 0.013) versus sel + dex. There were no statistically significant differences in ORR, TTR, and PFS. Belamaf had a favorable safety profile for most evaluable hematologic (any-grade, Grade 3-4) and non-hematologic (any-grade) adverse events versus sel + dex. Significantly improved OS was observed with belamaf versus SoC (0.29; 0.16, 0.54; p < 0.001). CONCLUSION: Single-agent belamaf represents a new treatment option for triple-class refractory patients with RRMM.

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

Rotavirus Efficacy and Safety Trial (REST) enrolled nearly 70,000 infants, of whom more than 23,000 were from Finland. REST determined the efficacy of the pentavalent rotavirus vaccine (RV5) against rotavirus-related hospitalisations and emergency department (ED) visits in the first year after vaccination. Finnish infants initially in REST transitioned into the Finnish Extension Study (FES), where they were followed for rotavirus-related hospitalisations and ED visits through their second year of life and beyond. FES identified 150 (31%) additional rotavirus gastroenteritis (RVGE) cases beyond those identified in REST in the Finnish participants. Overall, RV5 reduced RVGE hospitalisations and ED visits, regardless of the rotavirus serotype, by 93.8% (95% confidence interval [CI]: 90.8-95.9%) for up to 3.1 years following the last vaccine dose. Vaccine efficacy against combined hospitalisations and ED visits between ages 4 months to 11 months, 12 months to 23 months, and 24 months to 35 months was 93.9% (95% CI: 89.1-96.9%), 94.4% (95% CI: 90.2-97.0%), and 85.9% (95% CI: 51.6-97.2%), respectively. The reduction of hospitalisations and ED visits due to any acute gastroenteritis, rotavirus or not, was 62.4% (95% CI: 57.6-66.6%) over the entire follow-up period. The results from FES confirm that RV5 induces high and sustained protection against rotavirus-related hospitalisations and ED visits, and has a very substantial impact on all gastroenteritis-related hospitalisations and ED visits into the third year of life in Finnish children.

Comparative efficacy and safety and dolutegravir and lamivudine in treatment naive HIV patients.

OBJECTIVE: Compare the efficacy and safety of the 2-drug antiretroviral therapy regimen dolutegravir + lamivudine (DTG + 3TC) with traditional 3-drug regimens in treatment-naive patients with HIV-1. DESIGN: Data from double-blind, randomized controlled trials of at least 48 weeks' duration in treatment-naive patients with HIV-1 identified by systematic review were evaluated using a Bayesian network meta-analysis methodology. METHODS: The primary outcome was virologic suppression at Week 48 for 3-drug regimens versus DTG + 3TC (also analyzed in patient subgroup with baseline viral load >100 000 RNA copies/ml). Secondary outcomes included CD4 cell count change from baseline and safety (adverse events, serious adverse events, and drug-related adverse events) at Week 48. RESULTS: The network contains 14 unique regimens from 14 randomized controlled trials based on data from 10 043 patients. The proportional difference for viral suppression at 48 weeks for DTG + 3TC versus the other 13 regimens included in the network ranged from -2.7% (-11.0, 5.6%) versus DTG + tenofovir alafenamide/emtricitabine (FTC) to 7.3% (0.6, 13.8%) versus efavirenz + tenofovir disoproxil fumarate/FTC. DTG + 3TC was found to be significantly better than efavirenz + tenofovir disoproxil fumarate/FTC and similar to all other regimens analysed in terms of viral suppression at 48 weeks. With regard to other outcomes (CD4, adverse event, serious adverse event, drug-related adverse events) at 48 weeks, DTG+3TC was broadly similar to all regimens analysed. CONCLUSION: This network meta-analysis demonstrates similar efficacy and safety outcomes over 48 weeks with DTG + 3TC compared with traditional 3-drug antiretroviral therapy regimens.

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

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.

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

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

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.

Economic Evaluation of Boceprevir for the Treatment of Patients with Genotype 1 Chronic Hepatitis C Virus Infection in Hungary.

Background: Recent international, randomized, placebo-controlled clinical trials (SPRINT-2; RESPOND-2) demonstrated that the triple combination of peginterferon (PEG), ribavirin (RBV) and boceprevir (BOC) was more efficacious than the standard dual therapy of PEG and RBV in treatment of patients chronically infected with genotype 1 hepatitis C virus (HCV) infection. The objective of this study was to evaluate the cost-effectiveness of triple therapy in both treatment-naive and treatment-experienced patients in Hungary. Methods: A Markov model was developed to evaluate the long-term clinical benefits and the costeffectiveness of the triple therapy from the Hungarian payer perspective. Model states were fibrosis (F0-F4, defined using METAVIR fibrosis scores), decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), liver transplantation (LT), and liver-related deaths (LD). Efficacy was estimated from SPRINT-2 and RESPOND-2 studies. Disease progression rates and health state utilities used in the model were obtained from published studies. Estimates of probability of liver transplantation and cost were based on an analysis of the Hungarian Sick Fund database. All cost and benefits were discounted at 5% per year. Results: Compared to dual therapy, triple therapy was projected to increase the life expectancy by 0.98 and 2.42 life years and increase the quality-adjusted life years (QALY) by 0.59 and 1.13 in treatment-naive and treatment-experienced patients, respectively. The corresponding incremental cost-effectiveness ratios were HUF7,747,962 (€26,717) and HUF5,888,240 (€20,304) per QALY. The lifetime incidence of severe liver disease events (DC, HCC, LT, LD) were projected to decrease by 45% and 61% in treatment-naïve and treatment-experienced patients treated with triple therapy groups in comparison with PEG-RBV treatment. Conclusion: The addition of boceprevir to standard therapy for the treatment of patients with genotype 1 chronic HCV infection in Hungary is projected to be cost-effective using a commonly used willingness to pay threshold of HUF 8.46 million (3 times gross domestic product per capita).

Cost-effectiveness analysis of boceprevir for the treatment of chronic hepatitis C virus genotype 1 infection in Portugal.

BACKGROUND: The recent approval of two protease inhibitors, boceprevir and telaprevir, is likely to change the management of chronic hepatitis C virus (HCV) genotype 1 infection. OBJECTIVES: We evaluated the long-term clinical outcomes and the cost effectiveness of therapeutic strategies using boceprevir with peginterferon plus ribavirin (PR) in comparison with PR alone for treating HCV genotype 1 infection in Portugal. METHODS: A Markov model was developed to project the expected lifetime costs and quality-adjusted life-years (QALYs) associated with PR alone and the treatment strategies outlined by the European Medicines Agency in the boceprevir summary of product characteristics. The boceprevir-based therapeutic strategies differ according to whether or not the patient was previously treated and whether or not the patient had compensated cirrhosis. The model simulated the experience of a series of cohorts of chronically HCV-infected patients (each defined by age, sex, race and fibrosis score). All treatment-related inputs were obtained from boceprevir clinical trials - SPRINT-2, RESPOND-2 and PROVIDE. Estimates of the natural history parameters and health state utilities were based on published studies. Portugal-specific annual direct costs of HCV health states were estimated by convening a panel of experts to derive health state resource use and multiplying the results by national unit costs. The model was developed from a healthcare system perspective with a timeframe corresponding to the remaining duration of the patients' lifetimes. Both future costs and QALYs were discounted at 5 %. To test the robustness of the conclusions, we conducted deterministic and probabilistic sensitivity analyses. RESULTS: In comparison with the treatment with PR alone, boceprevir-based regimens were projected to reduce the lifetime incidence of advanced liver disease, liver transplantation, and liver-related death by 45-51 % and increase life expectancy by 2.3-4.3 years. Although the addition of BOC increased treatment costs by €13,300-€19,700, the reduction of disease burden resulted in a decrease of €5,400-€9,000 in discounted health state costs and an increase of 0.68-1.23 in discounted QALYs per patient. The incremental cost-effectiveness ratios of the boceprevir-based regimens compared with PR among previously untreated and previously treated patients were €11,600/QALY and €8,700/QALY, respectively. The results were most sensitive to variations in sustained virologic response rates, discount rates and age at treatment. CONCLUSIONS: Adding boceprevir to PR was projected to reduce the number of liver complications and liver-related deaths, and to be cost effective in treating both previously untreated and treated patients.

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 HbA(1c) value.

BACKGROUND: In a previously-published study, adding sitagliptin or glipizide to ongoing metformin therapy provided similar HbA(1c) 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 HbA(1c) 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 HbA(1c) 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 HbA(1c) 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 HbA(1c) 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 HbA(1c) 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.

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.