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Background: Abemaciclib was newly approved for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) high-risk early breast cancer (EBC). Clinical guidelines recommended abemaciclib as the first-line treatment for HR+/ HER2- EBC (early use) or HR+/ HER2- metastatic breast cancer (MBC) (delayed use)., Objective: To compare the cost-effectiveness of early vs delayed use of abemaciclib for treatment of HR+/HER2- high-risk EBC. Early use was defined as combined abemaciclib and endocrine therapy as first-line therapy for EBC, followed by treatment with fulvestrant for MBC. Delayed use was defined as endocrine therapy for EBC, followed by combined abemaciclib and fulvestrant therapy for MBC., Methods: A 5-state model was developed to estimate lifetime costs, life-years (LYs), and quality-adjusted life-years (QALYs) of hypothetical patients with HR+/ HER2- EBC from a third-party US payer's perspective. Key clinical and safety data were derived from the monarchE and MONARCH 2 clinical trials. Costs, utilities, and disutility values of adverse events were obtained from the literature. We calculated the incremental cost-effectiveness ratio (ICER) of early vs delayed abemaciclib use and compared it with a willingness-to-pay (WTP) threshold of $100,000 per LY or QALY. Deterministic and probabilistic sensitivity analyses (PSAs) were performed to test the robustness of the base-case model., Results: Base-case analysis showed early use yielded 21.08 LYs and 17.93 QALYs for $586,213 and delayed use yielded 11.14 LYs and 9.38 QALYs for $157,576. The ICER of early vs delayed use was $43,136/LY and $50,104/QALY, which was cost-effective at the WTP threshold of $100,000. The PSA result indicated that a 94.6% likelihood of early use (vs delayed use) was cost-effective at the WTP threshold of $100,000 per QALY., Conclusions: This study suggests that giving abemaciclib in the early stage rather than waiting until patients develop metastatic disease (current standard of care in MBC) is a cost-effective strategy.

Purpose: Incorporating adjuvant cyclin-dependent kinase (CDK) 4/6 inhibitors abemaciclib and ribociclib along with endocrine therapy has been shown to improve invasive disease-free survival (iDFS) for hormone receptor-positive (HR+) human epidermal receptor 2-negative (HER2-) early breast cancer (EBC). This study assesses the cost-effectiveness of this strategy, along with adjuvant aromatase inhibitors from an Indian perspective., Methods: A Markov chain model evaluated the cost-effectiveness of abemaciclib and ribociclib with letrozole compared with letrozole alone for HR+/HER2- EBC from a payer perspective in India. Key measures included lifetime quality-adjusted life-years (QALY), life-years (LY), and total costs. This study explores two scenarios for effectiveness: a best-case (BC) scenario, where the benefit of CDK4/6 inhibitors in improving iDFS lasts a lifetime, and a worst-case (WC) scenario, where benefits disappear after 5 years. Probabilistic sensitivity analyses (PSA) were used to account for simulation uncertainty., Results: In the BC scenario, abemaciclib added 2.17 QALY and 4.96 LY, incurring ₹2,317,957.7 ($27,756.65 in US dollars [USD]) in additional costs. However, the incremental cost-effectiveness ratio (ICER) for abemaciclib exceeded India's willingness-to-pay threshold in the BC and WC scenarios. In the BC scenario, ribociclib added 0.98 QALY and 2.58 LY with added costs of ₹1,711,504.32 ($20,494.6 USD). The ICER for ribociclib also surpassed India's threshold in both scenarios. PSA showed that neither drug was cost-effective at the current market prices in either BC/WC scenario. The cost of abemaciclib and ribociclib needs to be reduced by at least 78.61% and 87.19%, respectively, to be cost-effective in the BC scenario., Conclusion: The combination of adjuvant abemaciclib or ribociclib with letrozole is not cost-effective for HR+/HER2- EBC in India in either the BC or WC scenario.

Aims: We aimed to describe the clinical, economic, and societal burdens of cystic fibrosis (CF) and impact of CF transmembrane conductance regulator modulator (CFTRm) treatment on people with CF, caregivers, and healthcare systems., Material and Methods: This retrospective study used linked real-world data from Swedish national population-based registries and the Swedish CF Quality Registry to assess clinical, economic, and societal burden and CFTR impact in CF. Records from people with CF and a ten-fold control population without CF matched by sex, birth year, and location were compared during 2019. Outcomes for a subset aged >6 years initiating lumacaftor/ivacaftor (LUM/IVA) in 2018 were compared 12 months pre- and post-treatment initiation., Results: People with CF ( n  = 743) had >10 times more inpatient and outpatient specialist visits annually vs controls ( n  = 7406). Those aged >18 had an additional 77·7 (95% CI: 70·3, 85·1) days of work absence, at a societal cost of €11,563 (95% CI: 10,463, 12,662), while caregivers of those aged <18 missed an additional 6.1 (5.0, 7.2) workdays. With LUM/IVA treatment, people with CF ( n  = 100) had significantly increased lung function (mean change in ppFEV 1 [3·8 points; 95% CI: 1·1, 6·6]), on average 0·5 (95% CI: -0·8, -0·2) fewer pulmonary exacerbations and 45·2 (95% CI: 13·3, 77·2) fewer days of antibiotics. Days of work lost by caregivers of people with CF aged <18 decreased by 5·4 days (95% CI: 2·9, 7·9)., Conclusion: CF is associated with a high clinical economic and societal burden in Sweden. Improvements in clinical status observed in people with CF treated with LUM/IVA were reflected in reduced caregiver and societal burden.

Background: We conducted a cost-effectiveness analysis incorporating recent phase III clinical trial (MONALEESA-7) data to evaluate the cost-effectiveness of ribociclib (RIB) as a first-line treatment for premenopausal women with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) from the United States healthcare payer perspective. In addition, because RIB has not been marketed in China, we identified the range of drug costs for which RIB could be considered cost effective from a Chinese healthcare system perspective., Patients and Methods: A Markov model was developed to evaluate the cost-effectiveness of adding RIB to endocrine therapy over a lifetime. The clinical outcomes and utility data were obtained from published literature. Costs data were obtained from United States and Chinese official websites, and we determined the potential price for RIB in China based on its price in the United States. The main outcomes of this study were the incremental cost-effectiveness ratio (ICER) and quality-adjusted life-years (QALYs)., Results: The model projected that mean outcome was better with RIB and endocrine combined (3.83366 QALYs) than with endocrine therapy alone (2.71203 QALYs). In the United States, RIB and endocrine therapy cost an additional $604,960.06, resulting in an ICER of $539,357.95/QALY compared with endocrine monotherapy. Subgroup analyses indicated that, in China, the projected mean outcomes were better for RIB and endocrine therapy (6.37 QALYs) than for endocrine monotherapy (2.71 QALYs). The corresponding incremental costs were $224,731.88943. Thus, the ICER comparing RIB and endocrine therapy with endocrine therapy alone represented a $61,454.96/QALY gain., Conclusion: Additional use of RIB is estimated to not be cost effective as a first-line treatment for premenopausal women with HR-positive, HER2-negative ABC in the United States. A value-based price for the cost of RIB is less than $31.74/200 mg for China., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aim: To evaluate the cost-effectiveness of ribociclib plus fulvestrant versus fulvestrant in hormone receptor-positive/human EGF receptor 2-negative advanced breast cancer. Materials & methods: A three-state Markov model was developed to evaluate the costs and effectiveness over 10 years. Direct costs and utility values were obtained from previously published studies. We calculated incremental cost-effectiveness ratio to evaluate the cost-effectiveness at a willingness-to-pay threshold of $150,000 per additional quality-adjusted life year. Results: The incremental cost-effectiveness ratio was $1,073,526 per quality-adjusted life year of ribociclib plus fulvestrant versus fulvestrant. Conclusions: Ribociclib plus fulvestrant is not cost-effective versus fulvestrant in the treatment of advanced hormone receptor-positive/human EGF receptor 2-negative breast cancer. When ribociclib is at 10% of the full price, ribociclib plus fulvestrant could be cost-effective.

BACKGROUND: The 2015 American Society of Clinical Oncology guidelines recommend first-line treatment of hormone receptor (HR)-positive breast cancer with endocrine therapy plus or minus palbociclib, a selective cyclin-dependent kinase (CDK)4/6 inhibitor. In 2018, the U.S. Food and Drug Administration approved ribociclib, a new orally available selective CDK4/6 inhibitor. While gains in progression-free survival (PFS) and overall survival (OS) from ribociclib are important for clinical and treatment outcomes, trade-offs in adverse events (AEs) and additional costs necessitate cost-effectiveness analysis (CEA) to assist consideration by third-party payer systems, physicians, and patients. OBJECTIVES: To (a) develop a Markov model and (b) determine the cost-effectiveness of ribociclib plus endocrine therapy versus endocrine therapy alone as treatment for premenopausal and perimenopausal patients with HR-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. METHODS: A lifetime 3-state Markov model ("stable," "progressed," and "dead" health states) was developed using a U.S. payer perspective. Transition probabilities were calculated based on OS and PFS outcomes from the randomized controlled phase 3 trial MONALEESA-7. These Kaplan-Meier curves were extended to lifetime by estimating best-fit distributions using loglogistic distribution for ribociclib curves and Weibull distribution for placebo curves. Costs were obtained from national data sources using 2019 U.S. dollars (USD) and discounted by 3%. Utilities were obtained via published breast cancer literature and were included for each health state and for time spent with each AE. Results were expressed as an incremental cost-effectiveness ratio (ICER) expressed as USD per quality-adjusted life-year (QALY) saved. Treatments were assumed to be cost-effective based on a willingness-to-pay (WTP) threshold of $150,000 per QALY gained. Base-case, 1-way sensitivity tornado diagrams and probabilistic sensitivity analyses demonstrated changes in the ICER and were driven by the cost of ribociclib and the utility of remaining in the stable health state. RESULTS: Ribociclib plus endocrine therapy was cost-effective at an ICER of $124,513 per QALY when compared with endocrine therapy alone at a WTP threshold of $150,000. The ribociclib plus endocrine therapy arm had an effectiveness of 5.28 QALYs and a total cost of $385,112, while placebo plus endocrine therapy provided only 2.46 QALYs at a lower total cost of $67.246. The model was sensitive to the cost of ribociclib and the utility of time spent in the stable health state. Probabilistic sensitivity analysis demonstrated that endocrine therapy alone was cost-effective until a WTP of $125,000 and was cost-effective 72% of the time at the WTP threshold. CONCLUSIONS: Ribociclib plus endocrine therapy is more cost-effective than endocrine therapy alone. Professionals in managed care settings should consider the pharmacoeconomic benefits of ribociclib for the treatment of HR-positive, HER2-negative breast cancer as they make value-based formulary decisions. Further CEAs should be considered as direct treatment comparison trials between CDK4/6 inhibitors are completed in the future. DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose.

Background: CDK4/6 inhibitors have shown promising results for treating advanced breast cancer (ABC) and are routinely used in Singapore. In view of their high costs, it is important to assess their relative value compared to existing standards of care in the local setting., Aims: This study evaluates the cost-effectiveness of adding ribociclib to goserelin and a nonsteroidal aromatase inhibitor or tamoxifen as initial therapy for premenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) ABC in Singapore., Methods: A partitioned survival model with four health states (progression-free on first-line treatment, progression-free on second-line treatment, progressed disease, and death) was developed from a healthcare system perspective over a 10-year time horizon. Key clinical inputs were derived from the MONALEESA-7 trial, and survival curves were extrapolated beyond the trial period. Health state utilities were derived from the literature and direct medical costs were obtained from local public healthcare institutions. A discount rate of 3% was applied to both costs and outcomes. One-way deterministic and probabilistic sensitivity analyses were conducted to explore uncertainties., Results: The base-case analysis resulted in an incremental cost-effectiveness ratio (ICER) of SGD197, 667 per quality-adjusted life-year. Sensitivity analyses showed that the ICER was sensitive to the survival parametric distribution, ribociclib price, time horizon, and utility weights used. Even when these were varied, ICERs remained high and not cost-effective in the local context., Conclusion: At its current price, adding ribociclib to endocrine therapy is unlikely to be cost-effective in Singapore for HR+, HER2- ABC. Results from this study are useful to inform future funding decisions for CDK4/6 inhibitors alongside other factors including clinical effectiveness, safety, and budget impact considerations., (© 2020 The Authors. Cancer Reports published by Wiley Periodicals LLC..)

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Seidner, Rind, and Pearson are employed by ICER. Tice reports contracts to his institution, University of California, San Francisco, from ICER during the conduct of this study. Wherry has nothing to disclose.

Background: Lumacaftor-ivacaftor combination is a promising treatment for cystic fibrosis (CF) patients homozygous for the F508del-CFTR mutation. Optimal adherence is essential to achieve full health outcomes benefits., Methods: This retrospective study used pharmacy refills data to calculate proportion of days covered (PDC). Adherence was defined as a PDC ≥80%. A logistic regression analysis was conducted to examine factors associated with medication adherence., Results: Ninety-six patients were included in the final cohort for analysis. The mean PDC was 96%  ± 14 at 6 months, and 91% ± 17 at 12 months. The proportion of adherent patients was 89% and 83% at 6 and 12 months respectively. Age and ppFEV1 were found to affect medication adherence., Conclusions: Considering the medico-economic impact of CFTR modulator therapy, high adherence rates to lumacaftor-ivacaftor found in this study are encouraging., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interests., (Copyright © 2019 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: A common narrative is that high prices are necessary for "orphan drugs" because of the fewer patients. In the context of state health insurance systems, the high prices create significant challenges because of limited budgets., Results: This study carefully examines both costs and revenues of two drugs for cystic fibrosis (ivacaftor and lumacaftor), showing that, for this important example, prices are not high because of fewer patients. The study then explores the justifications usually given for high orphan drug prices, including the need to support research and development for new drugs. Each of these standard justifications is shown to be inadequate; instead, it appears that the exercise of market power in the presence of insurance is the dominant driver of high prices., Interpretation: Insurers need to re-examine how they address high-priced drugs., (Copyright © 2019 Longwoods Publishing.)

Background: Discarding unused drugs after dose changes or discontinuation can significantly affect pharmacy budgets. This is especially concerning for expensive oncology agents. However, few economic studies account for drug wastage, providing an inaccurate estimate of a drug's actual economic cost, cost-effectiveness, and value., Objectives: To (a) compare the economic impact of drug wastage between ribociclib and palbociclib-clinically similar oral medications for metastatic breast cancer-using 3 approaches (Markov model, pharmacy acquisition cost model, and a retrospective claims analysis) and (b) compare the modeling results with a published estimate of drug wastage for palbociclib from a claims analysis., Methods: A Markov model and a pharmacy acquisitions cost model were developed to evaluate the economic impact of dose reductions for ribociclib and palbociclib over a 1-year time period. Data inputs were pharmacy costs (RED BOOK wholesale acquisition cost) and proportion of patients experiencing dose reductions from either ribociclib randomized clinical trials (MONALEESA-2, -3, or -7) or real-world observational data (Symphony Health retrospective claims analysis). The latter constituted the third approach for quantifying drug wastage. The economic impact of dose reductions for ribociclib and palbociclib in postmenopausal women with previously untreated HR-positive/HER2-negative advanced breast cancer was assessed. Drug wastage was defined as drug doses that could not be used by a patient following a dose reduction. The cost of drug wastage was defined as the cost associated with an unused drug resulting from a dose reduction. The predicted results from the 2 models were compared with a previously published claims analysis that estimated the effect of treatment costs and drug wastage for palbociclib based on the observed dosing patterns from the Symphony Health Solutions database., Results: In the Markov model, relative to ribociclib, palbociclib users experienced drug wastage of $112,382 total, or $1,124 per treated patient, per year due to dose changes. In the pharmacy acquisition cost model, relative to ribociclib, palbociclib usage was associated with an increased cost of $7,196 per patient per year (based on a mid-cycle dose reduction) comprising dosing-based cost differences and drug wastage cost for palbociclib of $3,727. The previously published claims analysis found that palbociclib users experiencing a dose reduction had drug wastage costs of $5,471 per patient., Conclusions: In both models, dose reductions for ribociclib patients resulted in no wastage, since unused tablets could be administered in subsequent cycles, while dose reductions for palbociclib resulted in drug wastage and increased costs. The results from both models were consistent with previously published results from the claims analysis, demonstrating drug wastage costs for palbociclib., Disclosures: This study received financial support from Novartis Pharmaceuticals, which has products approved for treatment of breast cancer. Tang was employed by Novartis during this study; Zacker and Dalal are employed by Novartis and own company stock. Biskupiak, Brixner, and Oderda received payment from Novartis for this study. Brixner serves as a consultant for Millcreek Outcomes Group and also declares consulting fees from Abbvie, AstraZeneca, Abbott, Becton Dickinson, and Xcenda, unrelated to this study.

Purpose: Three CDK4/6 inhibitors, palbociclib (PAL), ribociclib (RIB), and abemaciclib, when combined with letrozole (LET), have been approved as first-line therapy for postmenopausal women with metastatic HR+, HER2- breast cancer. However, an economic evaluation of these newer therapies is currently lacking. The purpose of this article is to evaluate the cost-effectiveness of PAL or RIB for the treatment of advanced HR+, HER2- breast cancer in the United States., Methods: A Markov simulation model was constructed using data from published clinical trials evaluating PAL and RIB. Three simulated treatment strategies included PAL + LET, RIB + LET, or LET alone. The main outcome measures were simulated progression-free survival (PFS), overall survival (OS), costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs)., Results: Simulated median OS was 38.9 months for PAL + LET and 33.0 months for LET alone. Simulated median OS for RIB + LET was 43.3 months. Compared to LET alone, PAL + LET provided an additional 0.48 QALYs, on average, with an ICER of $634,000 per QALY gained; RIB + LET provided an additional 0.86 QALYs, on average, with an ICER of $440,000 per QALY gained. At current prices, neither PAL nor RIB was cost-effective, assuming a willingness-to-pay threshold of $100,000 per QALY gained. To reach such a cost-effectiveness threshold, PAL and RIB prices must decrease by approximately 70%., Conclusion: Despite significant gains in progression-free survival over letrozole alone, the addition of palbociclib or ribociclib in the treatment of advanced HR+, HER2- breast cancer is not cost-effective in the United States given current drug prices.

Three Cyclin Dependent Kinase 4/6 (CDK) inhibitors have been approved by the United Stated Food and Drug Administration for front line treatment of advanced hormone receptor positive breast cancer based on improvements in progression free survival against endocrine monotherapy. Two clinical trials have so far reported results on overall survival but both are negative. CDK inhibitors are usually tolerated well but they do add to inconvenience and cost - for example, grade III-IV neutropenia occur at a frequency of over 60% requiring frequent blood work at least during the initial months of treatment. These drugs cost over $ 13,500 for a 4-week cycle in the United States, and are responsible for billions of dollars annually in drug cost alone. Importantly, many women with metastatic breast cancer do well for a long time with endocrine therapy alone and CDK inhibitors do not have a predictive marker. Selective use of these agents in later lines may improve substantially the convenience and cost without compromise in overall outcome. However, with results demonstrating impressive improvements in PFS published in major medical journals coupled with patients' natural desire for "best available" options, the trend among oncologists is to prescribe these drugs as the default front-line treatment. In this commentary I caution readers against over interpretation of results from the CDK inhibitor trials, describe adverse consequences of routine front-line use, and explain why selective use in later line may yield a higher value., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The addition of ribociclib (RIB) to letrozole (LET) significantly increases progression free survival for patients with hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC). We identified the range of drug costs for which RIB could be considered cost effective from a Chinese perspective., Methods: A discrete event simulation model was developed to model the treatment sequences among patients with ABC. Life years (LYs), quality-adjusted LYs (QALYs) and lifetime costs were estimated. Costs were estimated for Chinese health care systems. Three times the per capita gross domestic product (GDP) of China 2016 ($24,360) and three times the per capita GDP of Beijing city 2016 ($53,384) were used as the willingness-to-pay threshold. Probabilistic sensitivity analyses were performed., Results: In the base case analysis, RIB + LET provided an incremental survival benefit of 0.631 LYs and 0.451 QALYs. When RIB costs less than $721 or $1170 per 4 weeks, there was a nearly 90% likelihood that the incremental cost-effectiveness ratio for RIB + LET would be less than $24,360 per QALY or $53,384 per QALY, respectively., Conclusion: A value-based price for the cost of RIB is $732 or $1170 per 4 weeks for China and Beijing City, respectively. Our study is helpful to inform the multilateral drug price negotiations in China that may be upcoming for RIB., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Cystic fibrosis (CF) is a chronic, progressive, genetic disease affecting more than 30,000 people in the United States and 70,000 people globally. The goals of treatment are to slow disease progression, reduce pulmonary exacerbations, relieve chronic symptoms, and improve the patient's quality of life. Lumacaftor/ivacaftor is a new therapy for CF that has demonstrated good clinical outcomes, including improved absolute percentage predicted forced expiratory volume in 1 second (FEV 1 %). However, given the high cost of therapy, there is a need to evaluate the overall value of lumacaftor/ivacaftor in CF management., Objectives: To (a) conduct a cost-effectiveness analysis (CEA) of lumacaftor/ivacaftor to understand the overall effectiveness of the drug compared with its costs and (b) conduct a budget impact analysis (BIA) to understand the potential financial effect of introducing a new drug in a health plan., Methods: Two static decision models were developed using Microsoft Excel to evaluate the cost-effectiveness and budget impact of lumacaftor/ivacaftor over a 1-year time frame from a payer perspective. Model inputs included drug costs (wholesale acquisition costs), drug monitoring schedules (package inserts), drug monitoring costs (Centers for Medicare & Medicaid physician fee schedule and published literature), FEV 1 % predicted and pulmonary exacerbation values (clinical trials), and cost to treat pulmonary exacerbations (published literature). The outcomes in the CEA included total cost of therapy; average cost-effectiveness ratio (ACER), defined as cost per FEV 1 % predicted; and incremental cost-effectiveness ratio (ICER), defined as the difference in the ratio of cost per FEV 1 % predicted of lumacaftor/ivacaftor and placebo. Outcomes in the BIA included total budget impact; cost per member per month (PMPM), defined as total budget impact per hypothetical plan population; and cost per treated member per month (PTMPM), defined as total budget impact per target CF population. All costs were adjusted to 2016 dollars, and one-way sensitivity analyses were conducted to test the model robustness given uncertainty in model inputs and study assumptions., Results: The annual cost of therapy per patient for lumacaftor/ivacaftor was $379,780. The ACER for lumacaftor/ivacaftor was $151,912, while the ICER for lumacaftor/ivacaftor compared with placebo was $95,016 per FEV 1 % predicted. The annual total budget impact due to the inclusion of lumacaftor/ivacaftor on the health plan formulary was $266,046. The PMPM cost was $0.02 and the PTMPM cost was $6.21., Conclusions: In patients with CF, lumacaftor/ivacaftor has demonstrated better clinical effectiveness compared with placebo alongside an increased drug acquisition cost. However, the therapy may be a viable alternative to existing standard therapy over a short time horizon. Health care payers, both private and public, need to evaluate the cost-effectiveness and the financial effect when considering expansion of new drug coverage in CF management., Disclosures: No outside funding supported this study. Covvey and Kamal have received research funding from Novartis Pharmaceuticals. Covvey, Giannetti, and Kamal have received research funding from the College of Psychiatric and Neurologic Pharmacists. Kamal serves as a consultant to the Lynx Group (Cranbury, NJ) and Manticore Consulting Group (Scottsdale, AZ). Mukherjee has nothing to disclose. A related poster abstract was presented at the AMCP Managed Care & Specialty Pharmacy Annual Meeting; March 27-30, 2017; Denver, CO.

Purpose: Patients with severe COPD are at high risk of experiencing disease exacerbations, which require additional treatment and are associated with elevated mortality and increased risk of future exacerbations. Some patients continue to experience exacerbations despite receiving triple inhaled therapy (ICS plus LAMA plus LABA). Roflumilast is recommended by the Global Initiative for Chronic Obstructive Lung Disease as add-on treatment to triple inhaled therapy for these patients. This cost-effectiveness analysis compared costs and quality-adjusted life-years for roflumilast plus triple inhaled therapy vs triple inhaled therapy alone, using data from the REACT and RE 2 SPOND trials., Patients and Methods: Patients included in the analysis had severe to very severe COPD, FEV 1 <50% predicted, symptoms of chronic bronchitis and ≥2 exacerbations per year. Our model was adapted from a previously published and validated model, and the analyses conducted from a UK National Health Service perspective. A scenario analysis considered a subset of patients who had experienced at least one COPD-related hospitalization within the previous year., Results: Roflumilast as add-on to triple inhaled therapy was associated with non-significant reductions in rates of both moderate and severe exacerbations compared with triple inhaled therapy alone. The incremental cost-effectiveness ratio (ICER) for roflumilast as add-on to triple inhaled therapy was £24,976. In patients who had experienced previous hospitalization, roflumilast was associated with a non-significant reduction in the rate of moderate exacerbations, and a statistically significant reduction in the rate of severe exacerbations. The ICER for roflumilast in this population was £7,087., Conclusions: Roflumilast is a cost-effective treatment option for patients with severe or very severe COPD, chronic bronchitis, and a history of exacerbations. The availability of roflumilast as add-on treatment addresses an important unmet need in this patient population.

Background: U.S. regulatory approvals of the cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors ribociclib and palbociclib as add-ons to letrozole greatly enhance the prospects for treating postmenopausal women with hormone receptor-positive (HR+)/human epidermal receptor 2-negative (HER2-) advanced or metastatic breast cancer. Clinical trials have established that the combination of a CDK 4/6 inhibitor with letrozole can significantly improve progression-free survival (PFS) versus letrozole monotherapy and is safe and well tolerated. Cost-effectiveness studies are required to inform payers and clinical decision makers on the money value of combination treatment in clinical practice., Objective: To evaluate the cost-effectiveness of ribociclib plus letrozole versus palbociclib plus letrozole and versus letrozole monotherapy in the first-line treatment of postmenopausal women with HR+/HER2- advanced or metastatic breast cancer from a U.S. private third-party payer perspective., Methods: A partitioned survival model including 3 health states (progression free, with either overall response or stable disease; progressed disease; and death) simulated lifetime costs and outcomes over a 40-year lifetime horizon with a 1-month cycle length. Clinical efficacy data (PFS and overall survival [OS]) were derived from a phase III trial of ribociclib plus letrozole (MONALEESA-2; NCT01958021), a phase II trial of palbociclib plus letrozole (PALOMA-1; NCT00721409), and a Bayesian network meta-analysis. Health care costs included drug acquisition and monitoring, disease management, subsequent therapies, and serious drug-related adverse events. Effectiveness was measured in life-years, derived from survival projections, and in quality-adjusted life-years (QALYs), calculated from time spent in each state combined with health-state utility values. A one-way deterministic sensitivity analysis explored the impact of uncertainty in key model parameters on results, and probabilistic uncertainty was assessed through a Monte Carlo probabilistic sensitivity analysis., Results: Ribociclib plus letrozole was dominant versus palbociclib plus letrozole, with a cost saving of $43,037 and a gain of 0.086 QALYs. Compared with letrozole monotherapy, ribociclib plus letrozole was associated with an incremental cost of $144,915 and an incremental QALY of 0.689, equating to an incremental cost-effectiveness ratio of $210,369 per QALY. Key model drivers included OS HRs for palbociclib plus letrozole versus letrozole and for ribociclib plus letrozole versus letrozole, the PFS HR for palbociclib plus letrozole versus letrozole, PD health-state costs, utility of response, and cost discount rate. The probabilities that ribociclib plus letrozole was cost-effective versus letrozole at thresholds of $50,000, $100,000 and $200,000 per QALY gained were 1.6%, 6.3%, and 50.5%, respectively., Conclusions: In the United States, ribociclib plus letrozole is a cost-effective alternative to palbociclib plus letrozole for the first-line treatment of postmenopausal women with HR+/HER2- advanced or metastatic breast cancer. Ribociclib plus letrozole is also cost-effective versus letrozole monotherapy at willingness-to-pay thresholds greater than $198,000 per QALY (for probabilistic analysis)., Disclosures: Funding for this study was provided by Novartis, which manufactures ribociclib and provided input on the study design and data collection, analysis, and interpretation. Mistry, May, Suri, and Young are employees of PAREXEL. Tang, Mishra, D. Bhattacharyya, and Dalal are employees of Novartis. S. Bhattacharyya was an employee of Novartis during the study period. Tang and Dalal hold stock in Novartis. Brixner, Oderda, and Biskupiak were paid by Millcreek Outcomes Group as consultants for work on this project. Brixner has also consulted for AstraZeneca, UCB, Regeneron, and Abbott.

Objectives: To forecast lifetime outcomes and cost of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis (CF) with homozygous phe508del mutation from the US payer perspective., Methods: A lifetime Markov model was developed from a US payer perspective. The model included five health states: 1) mild lung disease (percent predicted forced expiratory volume in 1 second [FEV 1 ] >70%), 2) moderate lung disease (40% ≤ FEV 1 ≤ 70%), 3) severe lung disease (FEV 1 < 40%), 4) lung transplantation, and 5) death. All inputs were derived from published literature. We estimated lumacaftor/ivacaftor's improvement in outcomes compared with a non-CF referent population as well as CF-specific mortality estimates., Results: Lumacaftor/ivacaftor was associated with additional 2.91 life-years (95% credible interval 2.55-3.56) and additional 2.42 quality-adjusted life-years (QALYs) (95% credible interval 2.10-2.98). Lumacaftor/ivacaftor was associated with improvements in survival and QALYs equivalent to 27.6% and 20.7%, respectively, for the survival and QALY gaps between CF usual care and their non-CF peers. The incremental lifetime cost was $2,632,249., Conclusions: Lumacaftor/ivacaftor increased life-years and QALYs in CF patients with the homozygous phe508del mutation and moved morbidity and mortality closer to that of their non-CF peers but it came with higher cost., (Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: Roflumilast is approved in the United States to reduce the risk of COPD exacerbations in patients with severe COPD. Exacerbation rates, health care resource utilization (HCRU), and costs were compared between roflumilast patients and those receiving other COPD maintenance drugs., Methods: LifeLink™ Health Plan Claims Database was used to identify patients diagnosed with COPD who initiated roflumilast (roflumilast group) or ≥3 other COPD maintenance drugs (non-roflumilast group) from May 1, 2011 to December 31, 2012. Patients must have been enrolled for 12 months before (baseline) and 3 months after (postindex) the initiation date, ≥40 years old, not systemic corticosteroid dependent, and without asthma diagnosis at baseline. Difference-in-difference models compared change from baseline in exacerbations, HCRU (office, emergency visits, and hospitalizations), and total costs between groups, adjusting for baseline differences., Results: A total of 14,211 patients (roflumilast, n=710; non-roflumilast, n=13,501) were included. During follow-up, the rate of overall exacerbations per patient per month decreased by 11.1% in the roflumilast group and increased by 15.9% in the non-roflumilast group (P<0.001). After controlling for baseline differences, roflumilast-treated patients experienced a greater reduction in exacerbations (0.0160 fewer exacerbations per month, P=0.01), numerically greater reductions in hospital admissions (0.003 fewer per month, P=0.57), office visits (0.46 fewer per month, P=0.26), and total costs from baseline compared with non-roflumilast patients ($116 less per month, P=0.62)., Conclusion: In a real-world setting, patients initiating roflumilast experienced reductions in exacerbations versus patients treated with other COPD medications.

Objective: Compare baseline characteristics, health care resource utilization (HCRU), and associated costs of COPD patients treated with add-on roflumilast with those of other combination medications., Design: Retrospective cohort study., Methodology: Patients aged 40 years with a diagnosis of chronic obstructive pulmonary disease (COPD) between March 1, 2011, and Nov. 30, 2012, were identified from the HealthCore Integrated Research Database and classified as roflumilast or nonroflumilast combination-therapy cohorts. Baseline characteristics were compared for all patients. HCRU and costs were compared between matched (M) roflumilast and nonroflumilast cohorts, using propensity score as a partial balancing score and then complementing the score with exact matching on specifically important variables. Generalized linear model and Poisson regression were used to estimate the adjusted differences in total costs and hospitalization rates, respectively, between the 2 matched cohorts., Results: A total of 695 roflumilast and 30,542 nonroflumilast combination therapy users were identified. At baseline, the roflumilast cohort had more complex COPD and a higher number of severe and moderate COPD exacerbations relative to the nonroflumilast cohort. After matching, the roflumilast (M) and nonroflumilast (M) cohorts (n = 328 in each) had similar mean age, gender distribution, and follow-up time. The roflumilast (M) cohort had significantly higher pharmacy-related, per-patient, per-month (PPPM) costs (P < .001) and similar total cost (P = .90). After adjusting for confounding variables, no difference was observed between the 2 cohorts in total costs (P = .86) and number of hospitalizations (P = .65)., Conclusion: Findings suggest that patients in the roflumilast cohort, relative to the nonroflumilast cohort, were more severely ill in the real-world setting. Despite higher pharmacy costs, the total cost for the roflumilast cohort was statistically similar to the nonroflumilast cohort. Future studies with longer follow-up are needed to evaluate the long-term economic impact of roflumilast use.

Background: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with declining lung function and health-related quality of life, and increased hospitalization and mortality. Clinical trials often poorly represent the elderly and thus have only partial applicability to their clinical care., Objective: To compare exacerbations, COPD-related health care utilization (HCU), and costs in a predominantly elderly Medicare COPD population initiated on roflumilast versus those not initiated on roflumilast., Methods: Deidentified administrative claims data from a large, national payer were utilized. Medicare patients aged 40-89 years with at least one COPD diagnosis from May 1, 2010 to December 31, 2012 were included. Members with at least one roflumilast pharmacy claim (index) were assigned to the roflumilast group and those without were assigned to the non-roflumilast group. Proxy index dates for the non-roflumilast group were randomly assigned for similar distribution of all patients' time at risk. Subjects with at least one pre-index COPD exacerbation had to be continuously enrolled for ≥365 days pre-index and post-index. Unadjusted and adjusted difference-in-difference (DID) analyses contrasted pre-index with post-index changes in exacerbations, HCU, and costs of roflumilast treatment compared with non-roflumilast treatment., Results: A total of 500 roflumilast and 60,145 non-roflumilast patients were included (mean age 69.7 and 72.3 years, respectively; P<0.0001). Unadjusted DID favored roflumilast for all exacerbations, with greater pre-index to post-index reductions in mean per 30-day COPD-related hospitalizations (-0.0182 versus -0.0013, P=0.009), outpatient visits (-0.2500 versus -0.0606, P<0.0001), and COPD-related inpatient costs (-US$141 versus -US$11, P=0.0346) and outpatient costs (-US$31 versus -US$4, P<0.0001). Multivariate analyses identified significantly improved pre-index to post-index COPD-related total costs (P=0.0005) and total exacerbations (P<0.0001) for the roflumilast group versus non-roflumilast group., Conclusion: In a predominantly elderly Medicare COPD population, newly initiated roflumilast patients displayed similar or significantly better unadjusted reductions in all exacerbation-related, COPD-related HCU-related, and COPD-related costs outcomes compared with non-roflumilast patients. These analyses also suggest better adjusted COPD-related costs and total exacerbations for roflumilast-initiated patients.

Background: Community-acquired pneumonia (CAP) is a major cause of death and morbidity worldwide. Treatment is centred on antibiotics with ceftriaxone and amoxicillin-clavulanate being some of the most commonly prescribed agents., Objective: To compare treatment outcomes and costs in patients receiving either of these two antibiotics at Witbank Hospital (WH)., Methods: A total of 200 randomly selected adult patient files (100 receiving ceftriaxone and 100 amoxicillin-clavulanate) recording a diagnosis of CAP were studied to determine the length of hospital stay, comorbid conditions and treatment outcomes. A descriptive and comparable analysis was performed., Results: Male gender, higher CURB-65 scores and death were associated with the use of ceftriaxone. Severity of disease and previous antibiotic exposure influenced the duration of hospital admission., Conclusion: Gender and severity of disease (based on the CURB-65 score) were the determinants of antibiotic choice at WH. Male gender increased the likelihood of being treated with ceftriaxone, as did a CURB-65 score of > 2. There were no differences in the outcomes of CAP patients treated with ceftriaxone compared with those treated with amoxicillin-clavulanate. Irrespective of antibiotic used, gender and severity of disease influenced treatment outcomes. Male gender was associated with a higher mortality and longer hospital stay. The average duration of stay for both antibiotics was not significantly different. Thus, only level 1 and 2 costs need to be considered when comparing the two regimens. On this basis, ceftriaxone was cheaper than amoxicillin-clavulanate.

Objective: To estimate the cost-effectiveness of adding a selective phosphodiesterase-4 inhibitor, roflumilast, to a long-acting bronchodilator therapy (LABA) for the treatment of patients with severe-to-very severe chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis with a history of frequent exacerbations from the UK payer perspective., Methods: A Markov model was developed to predict the lifetime cost and outcomes [exacerbations rates, life expectancy, and quality-adjusted life years (QALY)] in patients treated with roflumilast, which showed a reduction in the exacerbation rates and lung function improvement in a pooled analysis from two clinical trials, M2-124 and M2-125. Sensitivity analyses were conducted to explore the impact of uncertainties on the cost-effectiveness., Results: The addition of roflumilast to concomitant LABA reduced the number of exacerbations from 15.6 to 12.7 [2.9 (95 % CI 0.88-4.92) exacerbations avoided] and increased QALYs from 5.45 to 5.61 [0.16 (95 % CI 0.02-0.31) QALYs gained], at an incremental cost of £3,197 (95 % CI £2,135-£4,253). Cost in LABA alone and LABA + roflumilast were £16,161 and £19,358 respectively. The incremental cost-effectiveness ratios in the base case were £19,505 (95 % CI £364-£38,646) per quality-adjusted life-year gained and 18,219 (95 % CI £12,697-£49,135) per life-year gained. Sensitivity analyses suggest that among the main determinants of cost-effectiveness are the reduction of exacerbations and the case fatality rate due to hospital-treated exacerbations. Probabilistic sensitivity analysis suggests that the probability of roflumilast being cost-effective is 82 % at willingness-to-pay £30,000 per QALY., Conclusions: The addition of roflumilast to LABA in the treatment of patients with severe-to-very severe COPD reduces the rate of exacerbations and can be cost-effective in the UK setting.

Objective: To calculate the cost-effectiveness of roflumilast in combination with a long-acting beta agonist (LABA) versus LABA as a monotherapy in patients with severe and very severe COPD in Germany., Methods: The cost-effectiveness of Roflumilast plus LABA vs. LABA as monotherapy was calculated by a long-term model (Markov). The effectiveness data are based on the clinical trials AURA and HERMES (M2-124 and M2-125). Roflumilast plus LABA compared to LABA monotherapy reduced the exacerbation rate by 20.7 % (95 % CI, -31,-9) and improved post-bronchodilator FEV1 by 46 ml (2). These data were used to calculate the mean life expectancy of the COPD cohort (start age: 64 years). Costs for the treatment of exacerbations in the inpatient setting and the outpatient setting were included in the model. Endpoints were incremental costs per avoided exacerbation and per quality adjusted life year (QALY). The input variables were addressed in sensitivity analyses. German data on epidemiology and management of COPD were to populate the model and the cost-effectiveness was analyzed from the perspective of German statutory health insurance (SHI)., Results: The model predicts a mean life expectancy of 8.1 years for patients with roflumilast plus LABA and 7.8 years for patients with LABA alone. This corresponds with a gain of 0.26 life years or 0.23 QALYs. Within this time span patients receiving roflumilast plus LABA experienced 2.43 exacerbations less than the comparator group. The incremental cost for roflumilast plus LABA is €1,852 per exacerbation avoided and €19,457 per QALY gained., Conclusion: The model calculation indicates that the cost-effectiveness of roflumilast as an add-on to LABA in patients with severe and very severe COPD is comparable to the cost-effectiveness of established and reimbursed treatment options in Germany. Analogue consideration of the cost-effectiveness of the treatment options LAMA, LABA and ICS are advisable., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Chronic obstructive pulmonary disease (COPD) represents a burden on patients and health systems. Roflumilast, an oral, selective phosphodiesterase-4-inhibitor reduces exacerbations and improves lung function in severe/very severe COPD patients with a history of exacerbations. This study aimed to estimate the lifetime cost and outcomes of roflumilast added-on to commonly used COPD regimens in Switzerland., Methods: A Markov cohort model was developed to simulate COPD progression in patients with disease states of severe, very severe COPD, and death. The exacerbation rate was assumed to be two per year in severe COPD. COPD progression rates were drawn from the published literature. Efficacy was expressed as relative ratios of exacerbation rates associated with roflumilast, derived from a mixed-treatment comparison. A cost-effectiveness analysis was conducted for roflumilast added to long-acting muscarinic antagonists (LAMA), long-acting β2-agonist/ inhaled corticosteroids (LABA/ICS), and LAMA + LABA/ICS. The analysis was conducted from the Swiss payer perspective, with costs and outcomes discounted at 2.5% annually. Parameter uncertainties were explored in one-way and probabilistic sensitivity analyses., Results: In each of the comparator regimens mean life expectancy was 9.28 years and quality-adjusted life years (QALYs) gained were 6.19. Mean estimated lifetime costs per patient in the comparator arms were CHF 83,364 (LAMA), CHF 88,161 (LABA/ICS), and CHF 95,564 (LAMA + LABA/ICS) respectively. Adding roflumilast resulted in a mean cost per patient per lifetime of CHF 86,754 (LAMA + roflumilast), CHF 91,470 (LABA/ICS + roflumilast), and CHF 99,364 (LAMA + LABA/ICS + roflumilast), respectively. Life-expectancy and quality-adjusted life-expectancy were 9.63 years and 6.47 QALYs (LAMA + roflumilast), 9.64 years and 6.48 QALYs (LABA/ICS + roflumilast), and 9.63 years and 6.47 QALYs (LAMA + LABA/ ICS + roflumilast). Incremental cost-effectiveness ratios were CHF 12,313, CHF 11,456, and CHF 13,671 per QALY when roflumilast was added to the three regimens., Conclusion: Treatment with roflumilast is estimated to reduce the health and economic burden of COPD exacerbations and represent a cost-effective treatment option for patients with frequent exacerbations in Switzerland.

Purpose: Frequent exacerbations which are both costly and potentially life-threatening are a major concern to patients with chronic obstructive pulmonary disease (COPD), despite the availability of several treatment options. This study aimed to assess the lifetime costs and outcomes associated with alternative treatment regimens for patients with severe COPD in the UK setting., Patients and Methods: A Markov cohort model was developed to predict lifetime costs, outcomes, and cost-effectiveness of various combinations of a long-acting muscarinic antagonist (LAMA), a long-acting beta agonist (LABA), an inhaled corticosteroid (ICS), and roflumilast in a fully incremental analysis. Patients willing and able to take ICS, and those refusing or intolerant to ICS were analyzed separately. Efficacy was expressed as relative rate ratios of COPD exacerbation associated with alternative treatment regimens, taken from a mixed treatment comparison. The analysis was conducted from the UK National Health Service (NHS) perspective. Parameter uncertainty was explored using one-way and probabilistic sensitivity analysis., Results: Based on the results of the fully incremental analysis a cost-effectiveness frontier was determined, indicating those treatment regimens which represent the most cost-effective use of NHS resources. For ICS-tolerant patients the cost-effectiveness frontier suggested LAMA as initial treatment. Where patients continue to exacerbate and additional therapy is required, LAMA + LABA/ICS can be a cost-effective option, followed by LAMA + LABA/ICS + roflumilast (incremental cost-effectiveness ratio [ICER] versus LAMA + LABA/ICS: £16,566 per quality-adjusted life-year [QALY] gained). The ICER in ICS-intolerant patients, comparing LAMA + LABA + roflumilast versus LAMA + LABA, was £13,764/QALY gained. The relative rate ratio of exacerbations was identified as the primary driver of cost-effectiveness., Conclusion: The treatment algorithm recommended in UK clinical practice represents a cost-effective approach for the management of COPD. The addition of roflumilast to the standard of care regimens is a clinical and cost-effective treatment option for patients with severe COPD, who continue to exacerbate despite existing bronchodilator therapy.

Objective: To conduct a cost-effectiveness analysis comparing roflumilast/tiotropium therapy vs tiotropium monotherapy in patients with severe-to-very severe COPD., Methods: The economic evaluation applied a disease-based Markov cohort model with five health states: (1) severe COPD, (2) severe COPD with a history of severe exacerbation, (3) very severe COPD, (4) very severe COPD with a history of severe exacerbation, and (5) death. Within a given health state, a patient may have a mild/moderate or severe exacerbation or die. Data from roflumilast clinical trials and published literature were used to populate model parameters. The model calculated health outcomes and costs for roflumilast/tiotropium therapy vs tiotropium monotherapy over a 5-year horizon. Incremental cost and benefits were then calculated as cost-effectiveness ratios, including cost per exacerbation avoided and cost per quality adjusted life year ($/QALY)., Results: Over a 5-year horizon, the estimated incremental costs per exacerbation and per severe exacerbation avoided were $589 and $5869, respectively, and the incremental cost per QALY was $15,815. One-way sensitivity analyses varying key parameters produced an incremental cost per QALY ranging from $1963-$32,773., Limitations: A number of key parameters used in the model were obtained from studies in the literature that were conducted under different contexts. Specifically, the relative risk estimate for severe COPD patients originates from a small trial not designed to demonstrate the impact of roflumilast on frequency of exacerbations. In addition, the model extrapolates the relative risk estimates over periods of 5-30 years, even though the estimates were only observed in trials that spanned less than a year., Conclusions: The addition of roflumilast to tiotropium is cost-effective for the treatment of severe to very severe COPD patients.

Rationale: Roflumilast is an oral, once-daily phosphodiesterase IV (PDE4) inhibitor under investigation for chronic obstructive pulmonary disease (COPD). This study investigated the cost effectiveness of roflumilast in patients with severe to very severe COPD from the perspective of the UK society and UK NHS., Methods: The analysis was conducted alongside a 1-year, randomised, double-blind, placebo-controlled, multinational trial. The trial included 1514 COPD patients aged >or=40 years with a post-bronchodilator forced expiratory volume in 1 second (FEV1) % predicted