A descriptive cost-analysis of MYX.1/MCRN003, a phase 2 clinical trial evaluating high-dose weekly carfilzomib, cyclophosphamide, and dexamethasone in relapsed and refractory multiple myeloma.

BACKGROUND: The prevalence of multiple myeloma is increasing and there is a need to evaluate escalating therapy costs (Canadian Cancer Statistics A, 2020). The MYX.1 phase II trial showed that high-dose weekly carfilzomib, cyclophosphamide, and dexamethasone (wKCD) is efficacious in relapsed and refractory disease. We conducted a descriptive cost analysis, from the perspective of the Canadian public healthcare system, using trial data. METHODS: The primary outcome was the mean total cost per patient. Resource utilization data were collected from all 75 trial patients over a trial time horizon. Costs are presented in Canadian dollars (2020). RESULTS: The cost of treatment was calculated from the time of patient (pt) enrollment until the second data lock. The mean total cost was $203 336.08/pt (range $17 891.27-$505 583.55) Canadian dollars (CAD, where 1 CAD = 0.67 Euro (EUR)) and $14 081.45/pt per cycle. The median number of cycles was 15. The predominant cost driver was the cost of chemotherapy accounting for an average of $179 332.78/pt or $12 419.17/pt per cycle. Carfilzomib acquisition accounted for the majority of chemotherapy costs - $162 471.65/pt or $11 251.50/pt per cycle. Fifty-six percent (56%) of patients had at least one hospitalization during the trial period with an average cost of $12 657.86 per hospitalization. Three patients developed thrombotic microangiopathy (TMA) with an average cost of $18 863.32/pt including the cost of hospitalizations and therapeutic plasma exchange. CONCLUSIONS: High-dose wKCD is an active triplet regimen for relapsed and refractory multiple myeloma (RRMM) associated with reduced total cost compared with twice-weekly carfilzomib-based regimens.

Cost-effectiveness of once weekly carfilzomib 70 mg/m2 plus dexamethasone in patients with relapsed and refractory multiple myeloma in the United States.

BACKGROUND: In the US, carfilzomib 70 mg/m2 once-weekly plus dexamethasone (Kd70 QW) was recently indicated for relapsed and/or refractory multiple myeloma. In current US clinical practice, most patients treated with Kd receive carfilzomib at a previously approved dose of 27 mg/m2 twice-weekly (Kd27 BIW). This analysis assessed the cost-effectiveness (CE) of Kd70 QW vs Kd27 BIW regimens which were compared in the randomized phase 3 ARROW trial. METHODS: Based on clinical outcomes (overall survival and utilities) from ARROW, a partitioned survival model was developed to estimate life years (LYs) and quality-adjusted life years (QALYs). Long-term survival was extrapolated using SEER registry data matched to ARROW patients. Costs were estimated using a US healthcare payer perspective. RESULTS: The analysis estimated that treatment with Kd70 QW vs Kd27 BIW resulted in an increase of 1.10 LYs, 0.91 QALYs, and additional lifetime costs of $74,858, yielding an incremental CE ratio (ratio of incremental costs to QALYs) of $82,257 per QALY gained. Results were robust to sensitivity and subgroup analyses. CONCLUSIONS: When compared with Kd27 BIW, Kd70 QW is the optimal dose that represents a cost-effective utilization of health care budget with incremental CE ratios well below the accepted willingness-to-pay thresholds in the US.

Association of adverse events and associated cost with efficacy for approved relapsed and/or refractory multiple myeloma regimens: A Bayesian network meta-analysis of phase 3 randomized controlled trials.

BACKGROUND: Several new treatment options have been approved for relapsed and/or refractory multiple myeloma (RRMM). In this systematic review, associations of the efficacy of each approved regimen with adverse events (AEs) and the total cost per cycle were compared with a Bayesian network meta-analysis (NMA) of phase 3 randomized controlled trials (RCTs). METHODS: Scopus, Cochrane, PubMed Publisher, and Web of Science were searched from January 1999 to July 2018 for phase 3 RCTs of regimens (approved by the US Food and Drug Administration) used in RRMM. The relative ranking of agents was assessed with surface under the cumulative ranking (SUCRA) probabilities. The primary efficacy, safety, and cost outcomes were progression-free survival with the regimen, grade 3 to 4 AEs, and the total cost per cycle (regimen cost plus average cost of managing AEs). RESULTS: Fifteen studies including 7718 patients and evaluating 14 different regimens were identified. Daratumumab, lenalidomide, and dexamethasone were ranked highest for reducing progression (hazard ratio, 0.13; 95% credible interval, 0.09-0.19; SUCRA, 1) but carried the highest probability of total cost per cycle ($41,420; 95% Credible Interval [CrCl], $58,665-$78,041; SUCRA, 0.02). Panobinostat, bortezomib, and dexamethasone were the least effective and least safe (SUCRA, 0.24), whereas bortezomib, thalidomide, and dexamethasone emerged as least effective with the highest total cost per cycle (SUCRA, 0.33). Carfilzomib and dexamethasone emerged as the winner when this regimen was considered in terms of efficacy and safety (SUCRA, 0.61) and efficacy and total cost per cycle (SUCRA, 0.60). CONCLUSIONS: The results of this NMA can provide additional guidance for the decision-making process when one is choosing the most appropriate regimen for RRMM.

Effectiveness and Cost-Effectiveness of Triple Therapy With Telaprevir and Boceprevir for Chronic Hepatitis C: A Decision Analysis From the Brazilian Public Health System Perspective.

OBJECTIVES: Because of the lack of evidence regarding long-term effectiveness and cost-effectiveness of first-generation direct-acting antivirals for chronic hepatitis C (CHC) treatment in Brazil, we performed a cost-utility analysis comparing standard dual therapy (peginterferon plus ribavirin [pegIFN/RBV]), boceprevir, and telaprevir for CHC patients. METHODS: We developed a state-transition Markov model simulating the progression of CHC. Long-term outcomes included remaining life expectancy in life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Short-term outcomes included sustained virological response rates (SVR). Direct medical costs were obtained from Brazilian databases. A lifelong time horizon was considered and a 5% annual discount rate was applied for costs and clinical outcomes. A willingness-to-pay threshold of approximately $20 000 per QALY was used. We performed multiple sensitivity analyses. RESULTS: For short- and long-term scenarios, therapy with boceprevir was dominated by telaprevir, which was more effective than standard dual therapy (75.0% vs 40.4% SVR rate, 13.47 vs 12.59 LYs, and 9.74 vs 8.49 QALYs, respectively) and was also more expensive ($15 742 vs $5413). The corresponding ICERs were $29 854/SVR, $11 803/LY, and $8277/QALY. Based on our model, triple therapy with telaprevir was the most cost-effective treatment for the Brazilian health system. Despite a lack of data regarding the Brazilian population, we incorporated as many applicable parameters as possible. CONCLUSIONS: Telaprevir is more effective and cost-effective than boceprevir. Our model may be applied for other settings with a few adjustments in the input parameters.

Healthcare utilization and costs among relapsed or refractory multiple myeloma patients on carfilzomib or pomalidomide as monotherapy or in combination with dexamethasone.

Aim: To compare monthly healthcare resource utilization (HRU) and costs among adult patients with multiple myeloma (MM) receiving second or subsequent line of treatment (LOT) with carfilzomib or pomalidomide as monotherapy or in combination with dexamethasone. Methods and materials: Adult MM patients who received carfilzomib or pomalidomide as second/subsequent LOT between 2006 and 2014 were selected from the MarketScan databases. LOT was determined using Medical/pharmacy claims using a published algorithm. For each patient, first LOT with carfilzomib or pomalidomide was defined as index LOT. Patients with first LOT as index LOT, who received other chemotherapy in combination with carfilzomib or pomalidomide, or who underwent stem cell transplant (STC) during index LOT were excluded. Monthly HRU and costs during index LOT were compared using inverse probability of treatment weights (IPTW) based on propensity scores for receipt of carfilzomib estimated by logistic regression with LOT, patient demographics, Charlson index, comorbidities, pre-index healthcare cost, and receipt of prior SCT as covariates. Results: After weighting, baseline characteristics were well balanced among 114 carfilzomib and 144 pomalidomide patients. Mean (95% CI) numbers of outpatient visits per month were 7.1 (5.2-8.0) with carfilzomib and 4.7 (3.9-6.1) with pomalidomide (p = 0.006). Otherwise, there were no statistically significant differences between the groups in mean monthly HRU and costs or median time to therapy discontinuation. Mean (95% CI) monthly total healthcare costs were $19,776 (15,322-27,748) with pomalidomide and $17,321 (12,412-21,874) with carfilzomib (p = 0.522). Limitations: Comparison of carfilzomib vs pomalidomide may be biased if there are unobserved factors not balanced by IPTW. The relatively small sample size limits the power of analyses to detect potential differences between treatment groups. Conclusions: Monthly HRU and costs are similar among patients with relapse or refractory MM patients receiving carfilzomib or pomalidomide as monotherapy or in combination with dexamethasone.

Costs of administration, travelling, and productivity losses associated with hospital administration of multiple myeloma drugs in Finland.

AIM: To estimate the drug administration, travelling, and productivity costs associated with infusion or subcutaneous proteasome inhibitor (PI) treatments (specifically carfilzomib and bortezomib) for multiple myeloma (MM) patients in Finland. MATERIALS AND METHODS: Price tariffs of Finnish hospital districts are used as the basis of invoicing sent to healthcare service payers. A review of these price tariff lists was conducted and obtained data analysed to estimate the mean unit cost of PI administration visit. Travelling costs stratified by areas with different population densities were assessed, based on the national travelling reimbursement register data maintained by the Social Insurance Institution of Finland. Productivity costs due to time spent on administration visits and travelling were estimated based on an expert interview and a spatial healthcare accessibility analysis. RESULTS: Nineteen (95%) of the Finnish hospital districts were included in the review. Relevant unit cost information was found for 15 (75%) of the districts. The mean PI administration cost alone was 270€ (95% CI = 189€-351€) per administration and increased to 371€ when travelling costs were included. Productivity costs added, the mean PI administration costs totalled 405€ for bortezomib and 437€ for carfilzomib. LIMITATIONS: The costing rationale of price tariffs may vary between hospital districts. Productivity costs were estimated conservatively, due to lack of data. CONCLUSIONS: The administration of intravenous or subcutaneous PIs to treat MM in healthcare facilities causes significant and potentially avoidable healthcare, travelling, and indirect costs, and they should be included in all health economic evaluations (HEEs). As the cost estimates utilized in this study represent most of central hospitals in the country, they provide useful information for future HEEs. A broader conclusion is that novel oral medications, such as the first oral PI, have a significant potential for reducing administration-related costs of subcutaneous or intravenous PIs.

Modeling Covariate-Adjusted Survival for Economic Evaluations in Oncology.

BACKGROUND AND OBJECTIVES: In economic evaluations in oncology, adjusted survival should be generated if imbalances in prognostic/predictive factors across treatment arms are present. To date, no formal guidance has been developed regarding how such adjustments should be made. We compared various covariate-adjusted survival modeling approaches, as applied to the ENDEAVOR trial in multiple myeloma that assessed carfilzomib plus dexamethasone (Cd) versus bortezomib plus dexamethasone (Vd). METHODS: Overall survival (OS) data and baseline characteristics were used for a subgroup (bortezomib-naïve/one prior therapy). Four adjusted survival modeling approaches were compared: propensity score weighting followed by fitting a Weibull model to the two arms of the balanced data (weighted data approach); fitting a multiple Weibull regression model including prognostic/predictive covariates to the two arms to predict survival using the mean value of each covariate and using the average of patient-specific survival predictions; and applying an adjusted hazard ratio (HR) derived from a Cox proportional hazard model to the baseline risk estimated for Vd. RESULTS: The mean OS estimated by the weighted data approach was 6.85 years (95% confidence interval [CI] 4.62-10.70) for Cd, 4.68 years (95% CI 3.46-6.74) for Vd, and 2.17 years (95% CI 0.18-5.06) for the difference. Although other approaches estimated similar differences, using the mean value of covariates appeared to yield skewed survival estimates (mean OS was 7.65 years for Cd and 5.40 years for Vd), using the average of individual predictions had limited external validity (implausible long-term OS predictions with > 10% of the Vd population alive after 30 years), and using the adjusted HR approach overestimated uncertainty (difference in mean OS was 2.03, 95% CI - 0.17 to 6.19). CONCLUSIONS: Adjusted survival modeling based on weighted or matched data approaches provides a flexible and robust method to correct for covariate imbalances in economic evaluations. The conclusions of our study may be generalizable to other settings. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01568866 (ENDEAVOR trial).

Hepatitis C in Brazil: lessons learned with boceprevir and telaprevir.

In 2012, the first-generation protease inhibitors telaprevir (TVR) and boceprevir (BOC) were introduced in the Brazilian health system for treatment of chronic hepatitis C, after their approval by the National Committee for Health Technology Incorporation (CONITEC). However, these medicines were discontinued in 2015. The short period of use in therapy and their high cost require a discussion about the consequences for patients and for the health system of the early incorporation of new therapies. The article presents a qualitative analysis of the incorporation process of both medications in Brazil and the results of a multicenter study that included patients treated with BOC or TVR between January 2011 and December 2015 in five Brazilian cities. The study included 855 patients (BOC: n=247) and (TVR: n=608). The document analysis showed that CONITEC's decision to incorporate BOC and TVR was based on results of phase III clinical trials that compared sustained virologic response (SVR) rates of patients treated with BOC and TVR with rates of those that received placebo. However, these studies included a low percentage of cirrhotic patients. The SVR rates observed in this multicenter study were worse than clinical trials pointed out (BOC: 45.6%; TVR: 51.8%), but similar to those achieved with previously adopted therapies. The discontinuation rate due to adverse events was (BOC: 15.4%; TVR: 12.7%). Based on these unsatisfactory results, the study brings a discussion that goes beyond the therapy outcomes, exploring the incorporation of these high-cost medicines and the related decision-making process, contributing to future decisions in medicine policies and in the treatment of chronic hepatitis C.

Micro-costing analysis of guideline-based treatment by direct-acting agents: the real-life case of hepatitis C management in Brazil.

BACKGROUND: Eradication of hepatitis C virus (HCV) using direct-acting agents (DAA) has been associated with a financial burden to health authorities worldwide. We aimed to evaluate the guideline-based treatment costs by DAAs from the perspective of the Brazilian Ministry of Health (BMoH). METHODS: The activity based costing method was used to estimate the cost for monitoring/treatment of genotype-1 (GT1) HCV patients by the following strategies: peg-interferon (PEG-IFN)/ribavirin (RBV) for 48 weeks, PEG-IFN/RBV plus boceprevir (BOC) or telaprevir (TEL) for 48 weeks, and sofosbuvir (SOF) plus daclastavir (DCV) or simeprevir (SIM) for 12 weeks. Costs were reported in United States Dollars without (US$) and with adjustment for purchasing power parity (PPP$). Drug costs were collected at the National Database of Health Prices and an overview of the literature was performed to assess effectiveness of SOF/DCV and SOF/SIM regimens in real-world cohorts. RESULTS: Treatment costs of GT1-HCV patients were PPP$ 43,176.28 (US$ 24,020.16) for PEG-IFN/RBV, PPP$ 71,196.03 (US$ 39,578.23) for PEG-IFN/RBV/BOC and PPP$ 86,250.33 (US$ 47,946.92) for PEG-IFN/RBV/TEL. Treatment by all-oral interferon-free regimens were the less expensive approach: PPP$ 19,761.72 (US$ 10,985.90) for SOF/DCV and PPP$ 21,590.91 (US$ 12,002.75) for SOF/SIM. The overview reported HCV eradication in up to 98% for SOF/DCV and 96% for SOF/SIM. CONCLUSION: Strategies with all oral interferon-free might lead to lower costs for management of GT1-HCV patients compared to IFN-based regimens in Brazil. This occurred mainly because of high discounts over international DAA prices due to negotiation between BMoH and pharmaceutical industries.

Cost-effectiveness of Pomalidomide, Carfilzomib, and Daratumumab for the Treatment of Patients with Heavily Pretreated Relapsed-refractory Multiple Myeloma in the United States.

PURPOSE: Pomalidomide plus low-dose dexamethasone (POM-d), daratumumab monotherapy (DARA), and carfilzomib monotherapy (CAR) have been approved for use in the treatment of patients with heavily pretreated relapsed-refractory multiple myeloma (RRMM) in the US, based on findings from the MM-002, SIRIUS, and PX-171-003-A1 studies, respectively. The objective of this study was to assess the cost-effectiveness of POM-d, DARA, and CAR in this patient population from a US payer's perspective. METHODS: A cost-effectiveness model was developed to estimate the cost and health outcomes over a 3-year time horizon in 3 health states: progression-free, post-progression, and death. The main efficacy data source was a matching-adjusted indirect comparison using data from the aforementioned studies. Direct medical costs were considered, including: treatment acquisition and administration (initial line and subsequent line), pre- and post-medication, prophylaxis treatment, adverse event management, and health care resource utilization. Sensitivity analyses were conducted. A scenario analysis that assumed equal efficacy across all 3 treatments was conducted. Costs, life-years, and quality-adjusted life-years were estimated and discounted at 3% per annum. FINDINGS: Over 3 years, the use of POM-d was associated with similar life-years and quality-adjusted life-years gained compared with DARA and CAR (incremental: life-years, +0.02 and +0.07, respectively; quality-adjusted life-years, +0.01 and +0.05), and with a cost less than that of DARA (-$8,919) and similar to that of CAR (-$195). Sensitivity analyses illustrated that the results were sensitive to progression-free survival, treatment duration, and drug costs. An equal efficacy scenario resulted in cost-savings relative to those of both DARA and CAR (-$11,779 and -$12,595). IMPLICATIONS: POM-d may be a cost-effective treatment option relative to DARA or CAR in heavily pretreated patients with RRMM in the US.

[Cost effectiveness of GnRH antagonists in patients with prostate cancer and cardiovascular risk : Comparative analysis against Leuprorelin by the Number Needed to Treat]. / Kosteneffektivität von GnRH-Antagonisten bei Patienten mit Prostatakarzinom und kardiovaskulärem Risiko : Vergleichende Analyse gegenüber Leuprorelin anhand der Number Needed to Treat.

BACKGROUND: Recent studies suggest that androgen deprivation therapy (ADT) is associated with increased cardiovascular (CV) risk for patients with hormone-sensitive prostate cancer (PCa) and pre-existing CV disease. This risk seems to be different for the gonadotropin-releasing hormone (GnRH) agonists leuprolide and goserelin and GnRH antagonists, whereas the slightly more expensive GnRH antagonist shows a beneficial risk profile. The present study assesses the cost effectiveness of degarelix compared to leuprolide for PCa patients with increased CV risk. METHODS: This analysis is based on a pooled analysis of six phase III, randomized, controlled trials comparing the GnRH agonists leuprolide and goserelin with the GnRH antagonist degarelix. For the combined endpoint of CV events or death a superiority of degarelix was determined with a Number-Needed-to-Treat of 12. From the perspective of German statutory health insurance, this evaluation estimates and compares the additional drug costs of degarelix treatment to the cost of one (avoided) CV event. The CV event costs were estimated via emergency treatment and transportation, inpatient treatment, and rehabilitation. The difference of these two cost pools divided by 12 yields the average saving per patient and year. RESULTS: For every 12 PCa patients with CV history that are treated with GnRH antagonists to prevent one CV event, there will be additional drug costs in comparison with leuprolide treatment of € 3111 per year. Costs of € 8447 per year are prevented. Therefore, each patient with a history of CV who is treated with degarelix instead of a leuprolide generates savings of € 445 per patient and year. CONCLUSIONS: Compared to leuprolide, degarelix is cost effective for patients with increased CV risk.

Real-World Treatment Patterns, Time to Next Treatment, and Economic Outcomes in Relapsed or Refractory Multiple Myeloma Patients Treated with Pomalidomide or Carfilzomib.

BACKGROUND: Negligible real-world evidence exists for later line treatment of multiple myeloma (MM) to assist treatment decisions or reimbursement models, such as episode-based payments. OBJECTIVE: To describe the treatment patterns and clinical/economic outcomes when pomalidomide or carfilzomib is used for relapsed/refractory MM. METHODS: A U.S. claims database was used to identify MM patients with an initial pomalidomide or carfilzomib claim (index date) between February 1, 2013, and February 28, 2015, which was assumed to be relapse therapy. Treatment regimens were defined as all MM chemotherapy observed within 60 days of index. Patients receiving pomalidomide and carfilzomib within 60 days of index were excluded. Time to next treatment (TTNT), a progression proxy, was defined as the addition of a new agent > 60 days from index or as treatment restart following a > 90-day therapy gap. Cost estimations used plan-allowed amounts. Descriptive statistics were used to compare outcomes between treatment groups, and regression models were used to adjust for baseline patient characteristics. RESULTS: There were 454 patients initiating treatment with pomalidomide (n = 264) or carfilzomib (n = 190) during the index period. The most frequent initial regimens for pomalidomide patients included pomalidomide + dexamethasone (47.0%) and pomalidomide alone (33.0%); the most frequent regimens for carfilzomib patients were carfilzomib alone (45.3%) and carfilzomib + dexamethasone (14.7%). The most frequent next line treatment for pomalidomide patients who progressed was the addition of (14.0%) or switch to (15.0%) carfilzomib ± dexamethasone and for carfilzomib patients, the most frequent next line treatment was pomalidomide + dexamethasone (9.3%) and carfilzomib alone or carfilzomib + dexamethasone + cyclophosphamide (6.7% each). The median (95% CI) TTNT for pomalidomide patients was 11.9 (10.7-14.8) compared with 9.4 (7.7-10.0) months for carfilzomib (P = 0.060). For patients followed to progression (pomalidomide: n = 100, 37.9%; carfilzomib: n = 75, 39.5%), mean TTNT was longer for patients initiating therapy with pomalidomide (6.9 months) versus carfilzomib (5.3 months, P = 0.016). When adjusted for baseline confounders, pomalidomide patients had a nonsignificant longer time to a subsequent treatment line. Inpatient encounters observed during the index line were very low (mean = 1) for both groups; outpatient encounters were fewer in pomalidomide patients. Adjusted analyses revealed inpatient encounters were higher (P = 0.005), while outpatient use was lower in pomalidomide patients (P = 0.006). Unadjusted median costs incurred during the initial line were similar between the 2 groups (pomalidomide: $102,805; carfilzomib: $127,203; P = 0.110) but significantly lower in pomalidomide patients after adjusting for baseline characteristics (P = 0.013). Unadjusted per patient per month (PPPM) costs incurred over the entire follow-up period were lower in pomalidomide-initiated patients ($18,298 vs. $24,734, P = 0.001) but not statistically significant in adjusted analyses (P = 0.230). CONCLUSIONS: A longer time to a subsequent line of therapy was observed in pomalidomide patients compared with carfilzomib patients, although the difference lost significance in adjusted analyses. Compared with carfilzomib, pomalidomide patients were observed to have lower unadjusted median PPPM costs over the entire post-index period and lower adjusted mean monthly costs during initial therapy. DISCLOSURES: Funding for this study was provided by Celgene. Chen, McGuiness, and Wade are employees of QuintilesIMS, which was contracted by Celgene to undertake this research. McGuiness also owns stock in Pfizer. Parikh, Abouzaid, Purnomo, and Hussein are employees of Celgene and participated fully in the development and approval of the manuscript. Portions of the results of this research were previously presented at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting; June 3-7, 2016; Chicago, Illinois. Study concept and design were contributed by Chen, Parikh, Abouzaid, McGuiness, and Wade. Chen and McGuiness took the lead in data collection, along with Wade, and data interpretation was performed by Hussein and Wade, with assistance from the other authors. The manuscript was written by McGuiness, Chen, and Wade, with assistance from Parikh and Abouzaid, and revised by McGuiness and Hussein, along with the other authors.

Adoption of new agents and changes in treatment patterns for hepatitis C: 2010-2014.

OBJECTIVES: A number of new hepatitis C virus (HCV) medications have become available in the United States, but little is known about how these treatments have been adopted into practice and their financial burden on patients. The aim of this study was to examine whether the introduction of new HCV medications was associated with changes in treatment rates and out-of-pocket (OOP) costs. STUDY DESIGN: Retrospective analysis of administrative claims data from Optum Labs Data Warehouse. METHODS: We performed a retrospective analysis using a large, US commercial insurance database to identify 56,116 adults with chronic HCV between January 1, 2010, and December 31, 2014. Logistic regression was performed to calculate patients' predicted probability of being treated before and after the new medications became available. RESULTS: A total of 5436 (9.7%) of patients with HCV received treatment during an average of 1.8 years of follow-up. In the last quarter of 2014, 0.1% of patients with HCV received interferon/ribavirin as the primary treatment; no one received boceprevir or telaprevir, 1.1% received sofosbuvir combined with simeprevir, 1.4% received sofosbuvir or simeprevir alone, and 2.0% received ledipasvir/sofosbuvir. The introduction of new medications was significantly associated with an increased treatment rate, from 5.4% to 6.8% (P < .001). The increase was high among elderly patients and patients with liver transplant, liver cancer, and liver disease or cirrhosis. The median OOP costs of patients receiving new regimens were relatively low ($112-$340), but great variations existed. CONCLUSIONS: At the end of 2014, patients were almost exclusively using new therapies, which was associated with increased treatment rate, especially among patients who may need urgent treatment but are intolerant or ineligible for interferon-based regimens.

Drug Pricing Evolution in Hepatitis C.

OBJECTIVE: We aimed to determine the association between the stepwise increase in the sustained viral response (SVR) and Swiss and United States (US) market prices of drug regimens for treatment-naive, genotype 1 chronic hepatitis C virus (HCV) infection in the last 25 years. We identified the following five steps in the development of HCV treatment regimens: 1) interferon (IFN)-α monotherapy in the early '90s, 2) IFN-α in combination with ribavirin (RBV), 3) pegylated (peg) IFN-α in combination with RBV, 4) the first direct acting antivirals (DAAs) (telaprevir and boceprevir) in combination with pegIFN-α and RBV, and 5) newer DAA-based regimens, such as sofosbuvir (which is or is not combined with ledipasvir) and fixed-dose combination of ritonavir-boosted paritaprevir and ombitasvir in combination with dasabuvir. DESIGN: We performed a linear regression and mean cost analysis to test for an association between SVRs and HCV regimen prices. We conducted a sensitivity analysis using US prices at the time of US drug licensing. We selected randomized clinical trials of drugs approved for use in Switzerland from 1997 to July 2015 including treatment-naïve patients with HCV genotype 1 infection. RESULTS: We identified a statistically significant positive relationship between the proportion of patients achieving SVRs and the costs of HCV regimens in Switzerland (with a bivariate ordinary least square regression yielding an R2 measure of 0.96) and the US (R2 = 0.95). The incremental cost per additional percentage of SVR was 597.14 USD in Switzerland and 1,063.81 USD in the US. CONCLUSION: The pricing of drugs for HCV regimens follows a value-based model, which has a stable ratio of costs per achieved SVR over 25 years. Health care systems are struggling with the high resource use of these new agents despite their obvious long-term advantages for the overall health of the population. Therefore, the pharmaceutical industry, health care payers and other stakeholders are challenged with finding new drug pricing schemes to treat the entire population infected with HCV.

Cost-effectiveness of adding carfilzomib to lenalidomide and dexamethasone in relapsed multiple myeloma from a US perspective.

OBJECTIVE: To assess the economic value of carfilzomib (Kyprolis), this study developed the Kyprolis Global Economic Model (K-GEM), which examined from a United States (US) payer perspective the cost-effectiveness of carfilzomib-lenalidomide-dexamethasone (KRd) versus lenalidomide-dexamethasone (Rd) in relapsed multiple myeloma (RMM; 1-3 prior therapies) based on results from the phase III ASPIRE trial that directly compared these regimens. METHODS: A partitioned survival model that included three health states of progression-free (on or off treatment), post-progression, and death was developed. Using ASPIRE data, the effect of treatment regimens as administered in the trial was assessed for progression-free survival and overall survival (OS). Treatment effects were estimated with parametric regression models adjusting for baseline patient characteristics and applied over a lifetime horizon. US Surveillance, Epidemiology and End Results (1984-2014) registry data were matched to ASPIRE patients to extrapolate OS beyond the trial. Estimated survival was adjusted to account for utilities across health states. The K-GEM considered the total direct costs (pharmacy/medical) of care for patients treated with KRd and Rd. RESULTS: KRd was estimated to be more effective compared to Rd, providing 1.99 life year and 1.67 quality-adjusted life year (QALY) gains over the modeled horizon. KRd-treated patients incurred $179,393 in total additional costs. The incremental cost-effectiveness ratio (ICER) was $107,520 per QALY. LIMITATIONS: Extrapolated survival functions present the greatest uncertainty in the modeled results. Utilities were derived from a combination of sources and assumed to reflect how US patients value their health state. CONCLUSIONS: The K-GEM showed KRd is cost-effective, with an ICER of $107,520 per QALY gained against Rd for the treatment of patients with RMM (1-3 prior therapies) at a willingness-to-pay threshold of $150,000. Reimbursement of KRd for patients with RMM may represent an efficient allocation of the healthcare budget.

A Review of Potential Marine-derived Hypotensive and Anti-obesity Peptides.

Bioactive peptides are food derived components, usually consisting of 3-20 amino acids, which are inactive when incorporated within their parent protein. Once liberated by enzymatic or chemical hydrolysis, during food processing and gastrointestinal transit, they can potentially provide an array of health benefits to the human body. Owing to an unprecedented increase in the worldwide incidence of obesity and hypertension, medical researchers are focusing on the hypotensive and anti-obesity properties of nutritionally derived bioactive peptides. The role of the renin-angiotensin system has long been established in the aetiology of metabolic diseases and hypertension. Targeting the renin-angiotensin system by inhibiting the activity of angiotensin-converting enzyme (ACE) and preventing the formation of angiotensin II can be a potential therapeutic approach to the treatment of hypertension and obesity. Fish-derived proteins and peptides can potentially be excellent sources of bioactive components, mainly as a source of ACE inhibitors. However, increased use of marine sources, poses an unsustainable burden on particular fish stocks, so, the underutilized fish species and by-products can be exploited for this purpose. This paper provides an overview of the techniques involved in the production, isolation, purification, and characterization of bioactive peptides from marine sources, as well as the evaluation of the ACE inhibitory (ACE-I) activity and bioavailability.

Determinant Factors of the Direct Medical Costs Associated with Genotype 1 Hepatitis C Infection in Treatment-Experienced Patients.

OBJECTIVE: Limited evidence is available on predictors of medical resource utilization (MRU) and related direct costs, especially in treatment-experienced patients infected with genotype 1 hepatitis C virus (HCV). This study aimed at investigating patient and treatment characteristics that predict MRU and related non-drug costs in treatment-experienced patients with chronic hepatitis C (CHC) treated with simeprevir (SMV) or telapravir (TVR) in combination with pegylated interferon and ribavirin (PegIFN/R). PATIENTS AND METHODS: A total of 709 patients who completed the 72-week ATTAIN trial were included in the study. Cost data were analysed from the UK NHS perspective. Descriptive statistics and regression analyses were used to determine patterns and predictors of total MRU-related costs associated with SMV/PegIFN/R and TVR/PegIFN/R. RESULTS: Independent predictors for total MRU-related costs were age, region and the following interaction terms: (1) gender × F3-F4 METAVIR score × baseline viral load (BLVL), (2) body mass index (BMI) × F3-F4 METAVIR score × prior response to PegIFN/R and (3) gender × achievement of SVR at 12 weeks (SVR12) × BLVL. A F3-F4 METAVIR score was a stronger predictor of total MRU-related costs than SVR12. Predictors of adverse events included older age, female gender, low BMI, TVR/PegIFN/R and SVR12. Wilcoxon rank sum test revealed comparable total MRU-related costs between SMV/PegIFN/R and TVR/PegIFN/R. CONCLUSION: To the best of our knowledge, this study is the first to describe the relationship between commonly admitted predictors of MRU-related costs and their joint effect on total MRU-related costs in treatment-experienced patients with CHC. The identified predictors of MRU-related costs suggest that significant treatment costs can be avoided by starting treatment early before the disease progresses. Furthermore, adverse events seem to be the most important factor to take into consideration for the choice of treatment, especially when therapeutic options are associated with similar levels of medical resource utilization and associated costs.

[Cost-effectiveness and safety of telaprevir and boceprevir for chronic hepatitis C in real-world clinical practice]. / Coste-efectividad y seguridad de telaprevir y boceprevir para el tratamiento de la hepatitis C crónica en la práctica clínica.

INTRODUCTION: Triple therapy with telaprevir or boceprevir has proven to be effective in the treatment of chronic hepatitis C with response rates of up to 88%. However, the treatment may be associated with important adverse effects and a high economic impact. OBJECTIVE: To assess the cost-effectiveness and safety of triple therapy with telaprevir or boceprevir for the treatment of chronic hepatitis C. METHODS: Retrospective observational study. We included all patients who had started treatment with protease inhibitors before July 31(st), 2013. We evaluated sustained virological response, the cost per patient achieving sustained virological response, and the cost of the supportive treatment for adverse events associated with triple therapy. RESULTS: Fifty-nine patients were included; 35 had been treated with telaprevir (59.3%) and 24 with boceprevir (40.7%). Sustained virological response was achieved by 38 (64.4%) patients: 24 (68.6%) patients in the telaprevir treatment arm and 14 (58.3%) patients in the boceprevir treatment arm. The cost per patient with sustained virological response was 43,555 € (95% CI 35,389-51,722 €). There were no statistically significant differences between the overall costs of therapy with telaprevir, 43,494 € (95% CI 34,795 €-55,092 €) versus boceprevir, 42,005 € (95% CI 32,122-64,243€). The mean cost of supportive care per patient was 1,500 €, while the maximum cost was 11,374 €. Due to adverse events, 8 (13.6%) patients required hospital admission, 22 (37.3%) patients attended the accident and emergency department, and 26 (44.1%) patients needed additional medical consultations. CONCLUSIONS: The treatment of triple therapy with telaprevir or boceprevir resulted in high cost per patient with sustained virological response. Due to adverse events, a high number of patients required supportive care, whose costs should be added to those of triple therapy.

Direct costs of first-generation protease inhibitors for the treatment of genotype 1 chronic hepatitis C viral infection.

To evaluate the cost-effectiveness of Hepatitis C therapy, robust real-world data are needed to understand the costs and benefits of treatment alternatives. The objective of this study was to evaluate the true direct cost of treatment in an unselected sequential population of patients treated at a tertiary care centre for hepatitis C virus genotype 1. A total of 200 consecutive patients were treated with interferon, ribavirin and a first-generation direct-acting antiviral agent (DAA) between 2011 and 2013. A total of 41% had cirrhosis, 31% were prior relapsers, and 41% were prior partial or null responders. Costs used were wholesale acquisition cost prices for medications, average hospital costs per day for each diagnosis code based on US inpatient hospital charges. All costs were adjusted to 2013 dollars. Sustained virologic response (SVR) was achieved in 97 patients (48.5%). A total of 14% experienced relapse, 19% breakthrough or nonresponse, and 18.5% discontinued secondary to side effects. Twenty per cent of patients had at least one hospitalization attributable to a complication of therapy. Thirty-seven per cent of patients required erythropoietin-stimulating agents, 16% received filgastrim, and 15% needed a red blood cell transfusion. The mean overall cost of treatment was $83,851 per patient. The cost per SVR was $172,889; $266,670 for patients with cirrhosis. The costs per SVR after treatment with first-generation DAAs are dependent on the stage of disease and therapy side effects. These real-world costs significantly exceed those described in prior cost-effectiveness assessments and should be used instead for future studies.