Drug Administration Costs Research Articles

Comparative cost-effectiveness of tildrakizumab and other commonly used treatments for moderate-to-severe psoriasis

Objectives To compare the cost-effectiveness of tildrakizumab with other commonly used biologics and apremilast as the first-line treatment for moderate-to-severe plaque psoriasis from a US health plan’s perspective. Methods A 10-year cost-effectiveness model was developed to compare the incremental cost per extra month with a Psoriasis Area and Severity Index (PASI) 75 response. Patients were assumed to receive one of the treatments evaluated as their first-line treatment at the outset of the analysis. Nonresponders (PASI <75) discontinued their current treatment; 25% went on to receive a mix of topical therapies, phototherapies, and other systemic therapies, while 75% received a second-line therapy before receiving a mix of topical therapies, phototherapies, and other systemic therapies. Direct medical costs were calculated based on drug acquisition, administration, and monitoring costs. Results The incremental cost per extra month a patient had a PASI 75 response was lowest for brodalumab ($3,685), infliximab ($4,102), apremilast ($4,770), and tildrakizumab ($5,150), followed by risankizumab ($5,319), secukinumab ($5,675), guselkumab ($5,784), ixekizumab ($5,900), adalimumab ($5,943), ustekinumab ($6,131), etanercept ($6,618), and certolizumab pegol ($13,476). Conclusion Tildrakizumab was among the most cost-effective first-line treatments for moderate-to-severe psoriasis and was more cost-effective than risankizumab, secukinumab, guselkumab, ixekizumab, adalimumab, ustekinumab, etanercept, and certolizumab pegol.

Estimation of Total Costs in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma Receiving Tisagenlecleucel from a US Hospital's Perspective

INTRODUCTION: Diffuse large b-cell lymphoma (DLBCL) is a common and aggressive form of non-Hodgkin lymphoma (NHL). Relapsed/refractory (r/r) patients after two lines of therapy have limited treatment options and poor prognosis. In August 2018, tisagenlecleucel, a chimeric antigen receptor T-cell (CAR-T) therapy, received approval from the US Food and Drug Administration (FDA) for the treatment of r/r DLBCL after two or more lines of systemic therapy. Given the novel mechanism of action of tisagenlecleucel, there has been a need to understand the health resource use (HRU) and costs associated with such treatment. The current study aimed to estimate the total costs associated with tisagenlecleucel treatment in adult patients with r/r DLBCL from a US hospital's perspective. METHODS: An economic model was developed to assess the total costs associated with tisagenlecleucel treatment among adult patients with r/r DLBCL from a US hospital's perspective. The total costs were estimated from the time of leukapheresis to 2 months post-infusion, which is the timeframe when HRU related to the tisagenlecleucel infusion would likely occur. The model was developed using a fee-for-service approach, which estimated costs based on the HRU and safety data from the pivotal Phase 2 JULIET trial. The model considered costs of leukapheresis, lymphodepleting chemotherapy, tisagenlecleucel infusion and hospital administration, inpatient and intensive care unit (ICU) admission, medical professional visits, lab tests and procedures, and additional medication and HRU for the management of major adverse events (AEs) (e.g., cytokine release syndrome [CRS]). Medication costs were estimated using the wholesale acquisition cost from the Truven Redbook. Unit costs for drug administration and medical professional visits were from the Centers for Medicare &amp; Medicaid Services Physician Fee Schedule. Unit costs for AE were derived from the Healthcare Cost and Utilization Project. Lab tests, procedure costs, and daily inpatient and ICU costs were obtained from a hospital database analysis. All costs were inflation-adjusted to 2019 USD. The base-case model estimated the total costs using the observed hospitalization, ICU, and AE data from all patients receiving tisagenlecleucel infusion in the JULIET trial. Scenario analyses were conducted varying key assumptions related to AEs and hospitalization. RESULTS: The overall cost associated with the tisagenlecleucel treatment from leukapheresis to 2-months post infusion in r/r DLBCL patients were estimated at $437,927. Considering a list price of tisagenlecleucel at $373,000, the model calculated additional cost of care to be $64,784, which included $30,594 (47.2%) for AE management, $24,285 (37.5%) for inpatient and ICU not attributing to AEs, $5,443 (8.4%) for lab tests and procedure, $3,052 (4.7%) for lymphodepleting drug and administration, and $1,410 (2.2%) for medical professional visit. In the sensitivity analyses, the total costs ranged from $382,702 (no AEs, no hospitalization) to $469,006 (CRS and other AEs, hospitalization). CONCLUSIONS: This is the first US-focused study that comprehensively evaluated the costs associated with tisagenlecleucel treatment based on HRU data from clinical trial. The total cost within 2 months of tisagenlecleucel administration was estimated at $437,927, on average. Compared to the cost of tisagenlecleucel procedure, the non-drug cost is relatively small. Further research with estimates based on real-world clinical use of tisagenlecleucel is warranted. Disclosures Yang: Astellas: Other: I am an employee of Analysis Group, Inc., which provided paid consulting services to Astellas for the conduct of this study; Analysis Group, Inc.: Employment. Hao:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Chai:Analysis Group, Inc.: Employment; Novartis: Other: I am an employee of Analysis Group, Inc., which provided paid consulting services to Novartis for the conduct of this study. Qi:Analysis Group, Inc.: Employment; Astellas: Other: I am an employee of Analysis Group, Inc., which provided paid consulting services to Astellas for the conduct of this study. Wu:Novartis: Other: I am an employee of Analysis Group, Inc., which provided paid consulting services to Novartis for the conduct of this study.

PCN157 COST-EFFECTIVENESS ANALYSIS OF NIVOLUMAB + IPILIMUMAB VERSUS SUNITINIB IN THE FIRST-LINE TREATMENT OF ADVANCED OR METASTATIC INTERMEDIATE- OR POOR-RISK RENAL CELL CARCINOMA IN SPAIN

Nivolumab plus ipilimumab (nivolumab+ipilimumab) is the first immuno-oncology combination that has shown significant, long-term overall survival (OS) benefit for the first-line treatment of adult patients with intermediate- or poor-risk advanced renal cell carcinoma (1L RCC) compared with standard of care (sunitinib). This study assessed the cost-effectiveness of nivolumab+ipilimumab versus sunitinib in 1L RCC patients in Spain. A three-state partitioned survival model was developed (progression-free, progressed disease and death) with a lifetime horizon (40 years) and one-week cycle length. Progression-free survival, OS, time to treatment discontinuation, adverse event and treatment-specific utility data (EQ-5D-3L) was obtained from CheckMate-214 (NCT02231749; 30 months minimum follow-up). Spanish costs for adverse events and drug acquisition were obtained from Isla (2017) and CGCOF, respectively. Costs for drug administration, monitoring and subsequent therapies were taken from ESALUD (2018) ; associated resource use was based on CheckMate-214 and obtained through clinical expert input. An annual discount of 3.0% was applied to both costs and outcomes. Outcomes of interest were total costs, life years (LYs), quality-adjusted life-years (QALYs), and the incremental cost-utility ratio (ICUR). Furthermore, deterministic and probabilistic sensitivity analyses (DSA and PSA) were assessed for robustness of the results. Nivolumab+ipilimumab was associated with higher QALYs versus sunitinib (4.86 versus 3.54, respectively) at increased total cost (€142,450 versus €104,085, respectively). This resulted in an ICUR of €29,146/QALY versus sunitinib. Based on the DSA, the key ICUR drivers were the proportion of patients receiving treatment after sunitinib and the maximum treatment duration for nivolumab+ipilimumab. The model’s robustness was further confirmed by the PSA; nivolumab+ipilimumab had a 54% and 95% probability of being cost-effective at willingness-to-pay thresholds of €30,000/QALY and €50,000/QALY, respectively. Driven by the increased and sustained OS benefit demonstrated in CheckMate-214, nivolumab+ipilimumab is a cost-effective treatment when compared to sunitinib for 1L RCC patients in Spain, considering a willingness-to-pay of €30,000/QALY.

PCN170 COST-EFFECTIVENESS OF NIVOLUMAB IN COMBINATION WITH IPILIMUMAB COMPARED TO SUNITINIB IN THE FIRST-LINE TREATMENT OF ADVANCED OR METASTATIC INTERMEDIATE- OR POOR-RISK RENAL CELL CARCINOMA IN ITALY

Nivolumab in combination with ipilimumab (nivolumab+ipilimumab) is the first immuno-oncology combination that has shown significant, long-term overall survival (OS) benefit for the first-line treatment of adult patients with intermediate- or poor-risk advanced renal cell carcinoma (1L RCC) compared with standard of care (sunitinib). This study assessed the cost-effectiveness of nivolumab+ipilimumab compared with sunitinib in 1L RCC from a healthcare system perspective in Italy. A three-state partitioned survival model (progression-free disease, progressed disease, death) was developed with a 40-year time horizon and a one-week cycle length. Survival, adverse event, and treatment-specific utility (EQ-5D-3L) data were sourced from the CheckMate-214 trial (NCT02231749); survival was extrapolated over the model time horizon. Costs for adverse events, drug acquisition, drug administration, monitoring and subsequent therapies were obtained from the published literature, DRG tariffs and AIFA; while associated resource use was based on CheckMate-214 and obtained through clinical expert input. An annual discount of 3.0% was applied to both costs and effects. Outcomes of interest were total costs, life years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR). Furthermore, as a confidential discount already applies in Italy for both nivolumab and ipilimumab, two scenarios investigated the required price reduction on nivolumab+ipilimumab to reach an ICUR of €30,000/QALY and €20,000/QALY. Nivolumab+ipilimumab was associated with higher total LYs and QALYs (5.66 LYs and 4.89 QALYs) versus sunitinib (4.32 LYs and 3.63 QALYs) at increased total cost (€115,095 versus €61,226, respectively). This resulted in an ICER of €40,143/LY and an ICUR of €42,521/QALY versus sunitinib. Price reduction of 9.91% and 30.06% for nivolumab+ipilimumab would be required to reach ICURs of €30,000/QALY and €20,000/QALY, respectively. Driven by the increased and sustained OS benefit seen in CheckMate-214, nivolumab+ipilimumab is cost-effective versus sunitinib for the treatment of previously untreated 1L RCC in Italy.

PCN214 COST-EFFECTIVENESS ANALYSIS OF NIVOLUMAB IN COMBINATION WITH IPILIMUMAB VERSUS SUNITINIB FOR THE FIRST-LINE TREATMENT OF INTERMEDIATE- TO POOR-RISK ADVANCED RENAL CELL CARCINOMA IN FRANCE

Nivolumab in combination with ipilimumab (NIVO+IPI) is the first immuno-oncology combination to demonstrate significant, long-term overall survival (OS) benefit in previously untreated patients with intermediate- to poor-risk advanced renal cell carcinoma (1L RCC) compared with standard of care (sunitinib). The objective of this study was to assess the cost-effectiveness of NIVO+IPI compared with sunitinib in 1L RCC from the French all payers perspective. A three-state partitioned survival model (progression-free disease, progressed disease and death) was developed with a one-week cycle length and lifetime time horizon. The model used patient characteristics, progression-free survival, OS, safety data and utilities (EQ-5D-3L) from the CheckMate-214 trial (NCT02231749). French costs for drug acquisition, drug administration, monitoring, terminal care, travel and adverse events were sourced from published prices. Treatment-specific utilities were calculated using the French value set. Costs and outcomes were discounted by 4.0% annually. Univariate deterministic and multivariate probabilistic sensitivity analyses (DSA, PSA) assessed robustness of the results. Outcomes of interest were total costs, quality-adjusted life-years (QALYs), life years (LYs), the incremental cost-utility ratio (ICUR), and the incremental cost-effectiveness ratio (ICER). NIVO+IPI was associated with higher total QALYs and LYs (3.53 and 4.95) versus sunitinib (2.71 and 3.87) and increased total cost (€160,751 versus €86,596), all respectively. This resulted in an ICUR of €89,793/QALY gained and an ICER of €68,626/LY gained versus sunitinib. Based on the DSA, key model drivers were drug acquisition costs, QALY discount rate, and variation of OS function parameters (95% confidence interval). The PSA confirmed robustness of the model results, with NIVO+IPI having a 62% probability of being cost-effective at a willingness-to-pay (WTP) threshold of €100,000/QALY. Driven by an increased and sustained OS benefit, NIVO+IPI would be a cost-effective treatment when compared with sunitinib for 1L RCC patients in France at a WTP threshold of €100,000/QALY.

PCN72 COMPARATIVE COST ANALYSIS OF SUBCUTANEOUS TRASTUZUMAB ORIGINATOR (HERCEPTIN®) VS INTRAVENOUS TRASTUZUMAB BIOSIMILAR (KANJINTI) FROM A HOSPITAL PERSPECTIVE IN ITALY

The recent approval of the intravenous (IV) formulation of Kanjinti, biosimilar of Herceptin® (trastuzumab), offers patients suffering from HER2-positive early and metastatic breast cancer and metastatic gastric cancer an additional effective treatment option. Subcutaneous (SC) formulations of a medicine are generally perceived as more economic compared to IV mainly due to limited drug preparation time. The aim of this analysis was to compare the total medical costs for a hospital of treatment with subcutaneously injected Herceptin® and intravenously infused Kanjinti. A cost comparison model was developed to estimate the costs from a hospital perspective for 20 patients treated with both therapies over a 17-cycle period. The costs were collected in a single hospital institution in Italy and included drug acquisition and administration costs, consumables and compensation for the pharmacist’s time. For Kanjinti, the 420 mg pack was considered and public drug prices were used. Drug administration was reimbursed by the diagnosis-related group (DRG), which was the same for both SC and IV. Over 17 treatment cycles, the total costs with Kanjinti were estimated at €8,499 per patient vs. €17,929 with Herceptin® SC. Drug costs were the primary results driver (€12,012 vs. €21,497 with Kanjinti vs. Herceptin® SC, respectively), while pharmacist’s time and consumables comprised only a fraction of the total costs (1.5% vs. 0.4%, respectively). For the 20 patients considered per treatment option, the total costs with Kanjinti and Herceptin® SC amounted to €239,110 and €427,698, respectively, of which €2,508 and €1,393 were ancillary. The results of the present analysis suggest that when all relevant medical costs are considered, treatment with Kanjinti is associated with significant hospital budget savings compared to treatment with Herceptin® SC, contributing to longer term sustainability of the healthcare spending.

PCN189 COST-EFFECTIVENESS ANALYSIS OF PALBOCICLIB PLUS FULVESTRANT VERSUS EVEROLIMUS PLUS EXEMESTAN IN THE TREATMENT OF ESTROGEN RECEPTOR-POSITIVE, HER2-NEGATIVE, ADVANCED BREAST CANCER IN IRAN

Endocrine therapy continues to be the optimal systemic treatment for metastatic ER+/HER2- advanced breast cancer. The CDK4/6 inhibitor Palbociclib has recently been shown to significantly improve progression-free survival. The objective of this study was to assess the cost-effectiveness of Palbociclib plus Fulvestrant (PAL+FUL) versus Everolimus plus Exemestan (EVE+EXE) in the treatment of post-menopausal women with ER+/HER2- advanced breast cancer after failure of treatment with non-steroidal aromatase inhibitors (NSAIs) from an Iranian payer perspective. A Markov model was developed to evaluate the costs and effectiveness of PAL+FUL versus EVE+EXE over a 10-year time horizon. The model included 3 health states: responsive/stable disease, progression, or death. Monthly transition probabilities were estimated based on the published clinical trials and network meta-analyses. Time-to-progression and time-to-death were derived from a Weibull and exponential distribution. Direct medical costs including drug acquisition and administration costs, health states associated medical costs, and costs for managing adverse events (AEs) were put in the model. Utilities for each health state and disutilities for AEs were derived from the literature. Costs and effectiveness discounted at 7.2% and 5%, respectively. Finally, Incremental costs per quality-adjusted life years (QALYs) were estimated. One-way and probabilistic sensitivity analysis (PSA) were performed. PAL+FUL was associated with 1.79 QALYs and total direct costs of $22,517 over 10 years. Compared to EVE+EXE, PAL+FUL provided an additional 0.22 QALYs at an incremental cost of $440. The resulting incremental cost-effectiveness ratio was $1966/QALYs gained. A tornado analysis suggested that the key drivers of our model are Palbociclib and Everolimus acquisition costs. The PSA showed that assuming a willingness-to-pay of 1 GDP/capita ($5400), the probability of Palbociclib to be cost-effective was 65%. PAL+FUL can be considered cost-effective compared to EVE+EXE for the treatment of patients with HR+/HER2- metastatic breast cancer patients failing initial therapy with NSAIs in the Iranian healthcare system.

PCN114 ASSESSMENT OF THE SURVIVAL BENEFIT AND COST IMPACT OF NEW TREATMENTS FOR KEY ANSCLC BIOMARKERS USING THE ITEN MODEL

Five novel therapies (osimertinib, alectinib, brigatinib, dabrafenib and trametinib and pembrolizumab combination therapy) are expected to rewrite routine clinical management of advanced non-small cell lung cancer (aNSCLC) in Canada. These new front-line treatment options will alter treatment sequencing in later lines, but the impact of this is unknown. The impact of Treatment Evolution in NSCLC (iTEN) model is a validated discrete event patient simulation designed to estimate the impact of treatment sequencing in aNSCLC. The objective of this analysis was to estimate the survival and cost impact of these five novel therapies in Canada. A treatment algorithm to reflect ‘current’ treatment in 2018 was developed with Canadian clinical experts via a modified Delphi process. This algorithm was updated with expert input to identify likely treatment sequencing after first-line osimertinib for EGFR patients, first-line alectinib followed by brigatinib for ALK patients, first-line dabrafenib plus trametinib for BRAF patients and pembrolizumab plus chemotherapy for driver-mutation negative patients expressing PD-L1 below 50%. Clinical efficacy of treatments was estimated from Kaplan–Meier progression-free and overall survival data, as previously described (Moldaver et al. 2018). Modelled costs (2018 CDN $) included drug acquisition and administration costs and the costs of ongoing monitoring, imaging, physician visits, end-of-life, best supportive care, and adverse event management. A treatment rate of 100% in the first line and 60% thereafter was modelled. Introduction of these five therapies was estimated to incrementally increase the average 1-year survival of EGFR, ALK, BRAF and PD-L1<50% patients by 12%, 9%, 22%, and 1% respectively. Three-year survival was estimated to increase by 20%, 28%, 10% and 4%, respectively. The average life-time cost per-treated-patient, regardless of biomarker positivity, increased from $159,764 to $269,056. New aNSCLC treatment options are expected to increase the survival and cost of managing aNSCLC patients in Canada.

PGI31 SENSITIVITY OF INCREASING BODY WEIGHT IN PATIENTS WITH COLLITIS ULCEROSA TO TOTAL COST OF TREATMENT

A time-trend analysis of 40 clinical trials in Crohn’s disease showed a significant increase in the mean weight of patients from 57.5kg in 1997 to 89.1kg in 2008. The cost of current standard of care (SoC) for UC patients in Denmark is weight-dependent, in contrast to the newer therapeutic alternatives. Hence, the aim of this study is to analyze the sensitivity of body weight to total cost of treating UC patients in Denmark. We designed a total cost analysis including SoC infliximab, an anti-TNF, and two other mode of actions, an anti-integrin, vedolizumab and a JAK-inhibitor, tofacitinib. Drug costs were calculated using pharmacy purchasing prices assuming re-use of vials in the hospital setting (infliximab). Total cost included drug costs, hospital drug administration costs, patient time and travel costs. Both administration costs and patient’s costs were independent of weight. Patient education, monitoring of treatment effects and safety were assumed to be the same. Time horizon was 18 months and all costs after 12 months discounted by 4%. The analysis showed that the total cost of treating UC is sensitive to body weight. Total cost of treating patients for 18 months with SoC infliximab becomes more expensive than treating them with tofacitinib for patients above 81kg (tofacitinib DKK 135,573 and infliximab DKK 135,966). Cost of vedolizumab is not affected by weight and cost of treatment for 18 months is DKK 229.436. This study concludes that the total cost of treating UC patients in Denmark is sensitive to body weight, which affects the cost of drugs. For patients > 81kg, tofacitinib is a cheaper treatment option than current SoC. The current weight assumption guiding SoC in Denmark is 70kg. The results therefore suggest the need to revisit this assumption and possibly also the national medicine recommendations for UC.

Vaccination or mass drug administration against schistosomiasis: a hypothetical cost-effectiveness modelling comparison

BackgroundSchistosomiasis is a neglected tropical disease, targeted by the World Health Organization for reduction in morbidity by 2020. It is caused by parasitic flukes that spread through contamination of local water sources. Traditional control focuses on mass drug administration, which kills the majority of adult worms, targeted at school-aged children. However, these drugs do not confer long-term protection and there are concerns over the emergence of drug resistance. The development of a vaccine against schistosomiasis opens the potential for control methods that could generate long-lasting population-level immunity if they are cost-effective.MethodsUsing an individual-based transmission model, matched to epidemiological data, we compared the cost-effectiveness of a range of vaccination programmes against mass drug administration, across three transmission settings. Health benefit was measured by calculating the heavy-intensity infection years averted by each intervention, while vaccine costs were assessed against robust estimates for the costs of mass drug administration obtained from data. We also calculated a critical vaccination cost, a cost beyond which vaccination might not be economically favorable, by benchmarking the cost-effectiveness of potential vaccines against the cost-effectiveness of mass drug administration, and examined the effect of different vaccine protection durations.ResultsWe found that sufficiently low-priced vaccines can be more cost-effective than traditional drugs in high prevalence settings, and can lead to a greater reduction in morbidity over shorter time-scales. MDA or vaccination programmes that target the whole community generate the most health benefits, but are generally less cost-effective than those targeting children, due to lower prevalence of schistosomiasis in adults.ConclusionsThe ultimate cost-effectiveness of vaccination will be highly dependent on multiple vaccine characteristics, such as the efficacy, cost, safety and duration of protection, as well as the subset of population targeted for vaccination. However, our results indicate that if a vaccine could be developed with reasonable characteristics and for a sufficiently low cost, then vaccination programmes can be a highly cost-effective method of controlling schistosomiasis in high-transmission areas. The population-level immunity generated by vaccination will also inevitably improve the chances of interrupting transmission of the disease, which is the long-term epidemiological goal.

1582P - Estimating the cost and survival impact of new aNSCLC therapies in Canada with the iTEN model

BackgroundNovel therapies are replacing established treatment options for patients with advanced non-small cell lung cancer (aNSCLC), which poses a challenge to healthcare budgets. The impact of Treatment Evolution in NSCLC (iTEN) model is a validated discrete event patient simulation designed to estimate the impact of treatment sequencing in aNSCLC. The impact of five novel therapies (osimertinib, alectinib, brigatinib, dabrafenib and trametinib, and pembrolizumab combination therapy) changing aNSCLC management in Canada was modelled. MethodsCurrent Canadian treatment practices were established via a modified Delphi process with Canadian clinical experts. The table presents potential treatment sequences for biomarker positive aNSCLC with the novel therapies. Clinical efficacy of treatments was estimated from Kaplan–Meier progression-free and overall survival data, as previously described (Moldaver et al. 2018). Modelled costs (2018 CDN $) included drug acquisition and administration costs and the costs of ongoing monitoring, imaging, physician visits, end-of-life, best supportive care, and adverse event management. A treatment rate of 100% in the first-line and 60% thereafter was modelled.Table1582P Biomarker positive aNSCLC therapyTableEGFRALKBRAFPD-L1 ≥ 50%PD-L1 <50%1LOsimertinib*Alectinib*Dabrafenib plus trametinib*PembrolizumabPembrolizumab plus chemotherapy*2LPDBrigatinib*IO for those PD-L1 ≥ 50% PD for remainderPDDocetaxel3LI-OPDSwitch (PD to I-O and I-O to PD)DocetaxelErlotinib4LDocetaxel/BSCI-ODocetaxelErlotinib/BSCBSCTherapies with an asterisk (*) are new to Canada BSC, best supportive care; I-O, immuno-oncology agent; PD, platinum doublet chemotherapy ResultsIntroduction of these five therapies was estimated to increase the average 1- and 3-year survival of Canadian aNSCLC patients from 69% and 14% to 73% and 21%, respectively. Estimated average lifetime cost per treated patient rose from $159,764 to $269,056. ALK positive patients were estimated to have the largest increase in 3-year survival, from 35% to 64%, and cost of treatment, from $315,333 to $747,859. ConclusionsNew therapies for aNSCLC are likely to increase the survival and average cost of treatment in Canada. Legal entity responsible for the studyThe authors. FundingAstraZeneca Canada. DisclosureP.K. Cheema: Honoraria (self), Advisory / Consultancy: AstraZeneca Canada, BI, BMS, Roche, Pfizer, Novartis, Takeda and Merck,. W.K. Evans: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca Canada, AbbVie, Astellas, BMS, Eisai, Lilly, Janssen, Gilead, Takeda, Boehringer Ingelheim, Roche and Celgene. R. Burkes: Honoraria (self), Advisory / Consultancy: AstraZeneca Canada. R. Sangha: Honoraria (self), Advisory / Consultancy: Pfizer, BI, AZ, Roche/Genentech, Lundbeck, BMS, Merck, AbbVie and Takeda, Lilly, BMS, Novartis. C. Ho: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca Canada, Boehringer Ingelheim, Pfizer, BMS, Roche, Lilly, Genzyme, Eisai, Merck and Bayer. P. Wheatley-Price: Honoraria (self), Advisory / Consultancy, Leadership role: Novartis, BMS, Merck, AZ, Takeda, Roche and AbbVie. D. Boehm: Honoraria (self): AstraZeneca Canada, Baxter and Genomic Health. J. Venkatesh: Honoraria (self): AstraZeneca Canada, Takeda. S. Walisser: Honoraria (self), Advisory / Consultancy: stellas Pharma Canada, AstraZeneca Canada, Gilead Sciences Canada, Pfizer, and Janssen Inc. D. Grima: Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Cornerstone Research Group. D. Moldaver: Full / Part-time employment: Cornerstone Research Group. M. Hurry: Full / Part-time employment: AstraZeneca Canada.

Cost Effectiveness of PD-L1-Based Test-and-Treat Strategy with Pembrolizumab as the First-Line Treatment for Metastatic NSCLC in Hong Kong.

BackgroundPembrolizumab, a monoclonal antibody against programmed death ligand 1 (PD-L1), is approved by several regulatory agencies for first-line treatment of metastatic non-small-cell lung cancer (NSCLC) with a PD-L1 tumor proportion score (TPS) ≥ 50% and no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase genomic tumor aberrations. This study was conducted from the perspective of the Hospital Authority in Hong Kong and aimed to evaluate the cost effectiveness of a biomarker (PD-L1) test-and-treat strategy (BTS), in which patients with a TPS ≥ 50% received pembrolizumab and other patients received platinum doublet chemotherapy versus all patients receiving platinum doublet chemotherapy.MethodsThe model used a partitioned survival approach to estimate the incremental cost-effectiveness ratio (ICER) expressed as the cost per quality-adjusted life-year (QALY) gained. The clinical efficacy, utility and safety data were derived from the KN024 trial. Costs and health outcomes were projected over a 10-year time horizon and discounted at 3% per year. Costs for drug acquisition, PD-L1 testing, drug administration and disease management were used. Sensitivity analyses were conducted to evaluate the robustness of results.ResultsThe BTS approach led to an increase of 0.29 QALYs at an additional cost of Hong Kong dollars (HK$) 249,077 (US$31,933) compared with platinum doublet chemotherapy, resulting in an ICER of HK$865,189 (US$110,922) per QALY gained. This is lower than the World Health Organization cost-effectiveness threshold of three times the 2016 gross domestic product (GDP) per capita for Hong Kong of HK$1017,819 (US$130,490). Probabilistic sensitivity analyses showed a 59.4% chance that the ICER would be below this threshold.ConclusionFirst-line treatment with pembrolizumab in a BTS to identify patients with NSCLC with PD-L1 TPS ≥ 50% can be considered cost effective in Hong Kong compared with platinum doublet chemotherapy based on a three-times GDP per capita threshold. However, local data on clinical efficacy and safety were not available to estimate overall survival (OS) and progression-free survival (PFS) specific to patients with NSCLC in Hong Kong. Further, uncertainty is inherent in the survival projections/extrapolation of PFS and OS beyond the trial period, and future research may help to further inform these parameters.Electronic supplementary materialThe online version of this article (10.1007/s41669-019-00178-7) contains supplementary material, which is available to authorized users.

Resource implications of bortezomib therapy in a large UK cohort: An evaluation study.

Bortezomib is a cornerstone in the management of multiple myeloma. It remains an attractive treatment option because it is efficacious, reasonably well tolerated and easy to administer. However, data on resource implications in the UK for both patients and healthcare providers are limited. We conducted a retrospective study of 127 patients to assess implications of bortezomib therapy on patients and healthcare resources. A patient-episode was defined as a patient attending the chemotherapy day treatment unit solely for bortezomib administration. Data were collected for the duration of therapy as follows: cost of drug calculated using the UK's bortezomib indicative price as per British National Formulary, cost of drug administration in the chemotherapy day treatment unit calculated using the National Health Service's schedule of service cost, time from check-in to drug administration, patient travel time and distance calculated using Google maps, and cost of travel. Median drug cost and administration cost per patient were £8336 (£2084-£108,368) and £4640 (£290-£15,080), respectively. Median time from check-in to administration was 63 min (range 5-433), median travel time was 90 min (range 8-270) and 80 min (range 8-280) during peak and off-peak periods, respectively. Median return travel distance was 33.4 miles (range 1.2-224) for travel cost per patient per trip was £8.35-£13.20. Our real-world resource analysis demonstrated that delivering bortezomib therapy can be associated with significant cost and time implications for patients and healthcare providers. Our study method sets a basis for evaluating resource implications of other novel approaches to myeloma therapy.

Cost-effectiveness of pembrolizumab for the adjuvant treatment of resected high-risk stage III melanoma in the United States

Aims: To evaluate the cost-effectiveness of adjuvant pembrolizumab relative to observation alone following complete resection of high-risk stage III melanoma with lymph node involvement, from a US health system perspective.Materials and methods: A Markov cohort model with four health states (recurrence-free, locoregional recurrence, distant metastases, and death) was developed to estimate costs, life-years, and quality-adjusted life-years (QALYs) associated with pembrolizumab vs observation over a lifetime (46-year) horizon. Using a parametric multi-state modeling approach, transition probabilities starting from recurrence-free were estimated based on patient-level data from KEYNOTE-054 (NCT02362594), a direct head-to-head phase 3 trial. Post-recurrence transition probabilities were informed by real-world retrospective data and clinical trials in advanced melanoma. Health state utilities and adverse event-related disutility were derived from KEYNOTE-054 trial data and published literature. Costs of drug acquisition and administration, adverse events, disease management, and terminal care were estimated in 2018 US dollars. Deterministic and probabilistic sensitivity analyses were conducted to assess robustness.Results: Over a lifetime horizon, adjuvant pembrolizumab and observation were associated with total QALYs of 9.24 and 5.95, total life-years of 10.54 and 7.15, and total costs of $489,820 and $440,431, respectively. The resulting incremental cost-effectiveness ratios (ICERs) for pembrolizumab vs observation were $15,009/QALY and $14,550/life-year. Across the range of input values and assumptions tested in deterministic sensitivity analyses, pembrolizumab ranged from being a dominant strategy to having an ICER of $57,449/QALY vs observation. The ICER was below a willingness-to-pay threshold of $100,000/QALY in 90.2% of probabilistic simulations.Limitations: Long-term extrapolation of outcomes was based on interim results from KEYNOTE-054, with a median follow-up of 15 months.Conclusions: Based on common willingness-to-pay benchmarks, pembrolizumab is highly cost-effective compared with observation alone for the adjuvant treatment of completely resected stage III melanoma in the US.

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.

Sarilumab monotherapy compared with adalimumab monotherapy for the treatment of moderately to severely active rheumatoid arthritis: an analysis of incremental cost per effectively treated patient.

PurposeTreatment outcomes and direct medical costs were examined, from a US health payer perspective, of monotherapy with sarilumab 200 mg subcutaneous (SC) every 2 weeks (Q2W) vs adalimumab 40 mg SC Q2W/QW in adult patients with moderately to severely active rheumatoid arthritis who are intolerant of, inadequate responders to, or considered inappropriate candidates for continued methotrexate treatment.Patients and methodsShort-term analysis was based on 24-week wholesale acquisition costs of drugs and treatment response observed in the MONARCH Phase III trial (NCT02332590) per American College of Rheumatology (ACR) 20/50 criteria and European League Against Rheumatism (EULAR) Moderate/Good Disease Activity Score 28-joint count erythrocyte sedimentation rate. Long-term analysis, which also considered drug administration and routine care costs, was conducted via a 6-month decision tree and a 1- to 10-year Markov model with microsimulation of patient profiles from the MOBILITY Phase III trial (NCT01061736). Utilities and quality-adjusted life-years (QALYs) were estimated by mapping 6-month ACR levels to a relative change in Health Assessment Questionnaire – Disability Index score and via published algorithms.ResultsFor sarilumab and adalimumab, respectively, 24-week drug costs were $18,954 and $29,232, and costs per responder were $26,435 vs $50,055 on ACR20; $41,475 vs $98,425 on ACR50; and $22,511 vs $41,230 on EULAR Moderate/Good. Base case results at 10 years for total costs and QALYs were $176,977 and 2.75 for sarilumab and $212,136 and 2.61 for adalimumab, respectively. Sarilumab was consistently the more effective and cost-saving treatment across all short-term and long-term incremental analyses.ConclusionSarilumab monotherapy was the economically dominant treatment on incremental cost per responder and incremental cost per QALY compared with adalimumab monotherapy. These results were maintained within the sensitivity analyses.

A Budget Impact Analysis of the Introduction of Copanlisib for Treatment of Relapsed Follicular Lymphoma in the United States.

Copanlisib was recently granted accelerated approval by the FDA for the treatment of adult patients with relapsed follicular lymphoma (FL) after 2 previous systemic therapies. It is important to assess the effect that this and other changes in the treatment landscape of relapsed FL have on a payer's budget to inform formulary decisions. To assess the budget impact associated with the addition of copanlisib to a formulary as third- or higher-line treatment for adult patients with relapsed FL who have received at least 2 previous systemic therapies, from the perspective of a U.S. third-party payer. A budget impact model was developed over a 1-year horizon. The model considered a hypothetical population of 1 million people enrolled in a commercial health plan; patients with relapsed FL were identified based on epidemiology data. Treatments included copanlisib and approved and off-label therapies used for management of relapsed FL. Treatment distributions within the target population were based on a market research survey. Drug acquisition, administration, prophylaxis, and monitoring costs were based on prescribing information, clinical trials, literature, and expert opinion. All costs were inflated to 2017 U.S. dollars. Total costs were compared between 2 scenarios, 1 without and 1 with copanlisib on a formulary. A deterministic sensitivity analysis (DSA) was conducted to evaluate the robustness of the model. Within the 1 million-member health care plan, 18 patients had relapsed FL and had received at least 2 previous systemic therapies. Over 1 year, the addition of copanlisib and an increase in the use of obinutuzumab + bendamustine (from 9.0% without copanlisib to 13.1% with copanlisib) and lenalidomide + rituximab (from 0.3% to 12.0%) were estimated to increase drug acquisition costs by $238,536, drug administration and prophylaxis costs by $3,565, and monitoring costs by $539. The increase in total budget was $242,641, corresponding to $0.02 per member per month; 21.8% of this increase was attributable to copanlisib, 12.9% to obinutuzumab + bendamustine, and 65.3% to lenalidomide + rituximab. Results were generally robust in the DSA. Over a 1-year period, the model found that the addition of copanlisib to a formulary resulted in a small increase in total budget of $242,641, corresponding to $0.02 per patient per month and taking into account a concurrent increase in the use of obinutuzumab + bendamustine and lenalidomide + rituximab. Therefore, adding copanlisib to a formulary appears to be an affordable option for payers. Further studies should be conducted to more comprehensively assess the clinical and economic implications of adding copanlisib to the treatment armamentarium of relapsed FL. This study was funded by Bayer HealthCare Pharmaceuticals. The study sponsor was involved in study design, data interpretation. and data review. All authors contributed to the development of the manuscript and maintained control over the final content. Appukkuttan, Yaldo, Gharibo, and Babajanyan report employment with Bayer HealthCare Pharmaceuticals at the time of this study. Duchesneau, Zichlin, Bhak, and Duh report employment with Analysis Group, which received research funds from Bayer HealthCare Pharmaceuticals for work on this study. A synopsis of the current research was presented in poster format at the AMCP Managed Care & Specialty Pharmacy Annual Meeting; April 23-26, 2018; Boston, MA.

Costs of sequential multiple myeloma treatment for elderly transplant-ineligible patients in the Serbian health care system

Introduction. Multiple myeloma is an incurable plasma-cell pro?liferation mainly affecting the elderly population. The aim of this study was to analyze treatment patterns, utilization of health resources and treatment costs of multiple myeloma in the elderly patients ineligible for autologous hematopoietic stem cell transplantation in Serbia. Material and Methods. The analysis of the health?care costs, from the perspective of the Serbian healthcare system, took into account the costs of medications, diagnostic procedures, inpatient and outpatient care, as well as the costs of drug administration and management of drug adverse effects. Results. Thalidomide based regimens were less costly than bortezomib-based regimens (average per-protocol costs 6,000 ? vs. 64,700 ?, respectively). The most expensive treatment regimen was lenalidomide-dexamethasone (average per-protocol costs 145,200 ?). The sequential (four-line therapy) treatment costs varied from 85,800 ?, starting with melphalan-prednisone-thalidomide to 153,800 ?, starting with melphalan-prednisone-bortezomib. The estimated costs did not significantly differ during variation of the parameters in the sensitivity analysis. Conclusion. The costs of multiple myeloma treatment in the Republic of Serbia are mainly driven by the cost of antimyeloma drugs. The most expensive treatment sequence was starting with melpha1an-prednisone-bortezomib treatment protocol.

Cost-Effectiveness Analysis of Lenalidomide for Maintenance Therapy after Autologous Stem Cell Transplant (ASCT) in Newly Diagnosed Multiple Myeloma (NDMM) Patients: A United States Payer Perspective

Introduction: ASCT in multiple myeloma (MM) is associated with prolonged progression-free survival (PFS) compared with chemotherapy alone. Studies have shown that lenalidomide maintenance therapy after ASCT significantly improves PFS and overall survival (OS) in patients (pts) with NDMM. Although post-ASCT lenalidomide maintenance therapy is approved by the US FDA and the EMA for pts with MM, a small percentage of pts either use bortezomib or no maintenance in this setting. The current study aimed to assess the cost-effectiveness of lenalidomide maintenance versus no treatment or bortezomib maintenance after ASCT in pts with NDMM from a US third-party payer perspective.Methods: A partitioned survival model with a 28-day cycle was developed to estimate costs and outcomes of lenalidomide maintenance versus either no treatment or bortezomib maintenance therapy after ASCT among pts with NDMM over a lifetime time horizon. The model included four health states: PFS on treatment, PFS off treatment, progressed disease, and death. The OS and PFS for lenalidomide and no treatment arms were estimated using observed data from the phase 3 CALGB trial. Crossover adjustment was implemented to adjust for the potential diluting effects introduced by pts crossing over to lenalidomide from the no treatment arm before progression in the CALGB trial. Time on treatment for lenalidomide was estimated using the observed data in the pooled phase 3 trials (CALGB, IFM, GIMEMA). Efficacy inputs for bortezomib maintenance were estimated based on published literature. Standard parametric models were fitted to extrapolate OS and PFS for each treatment, and best fit was determined based on Akaike or Bayesian information criterion and clinical judgement. OS was adjusted using natural mortality rates in the USA. Treatment costs (including drug and drug administration costs), post-progression treatment costs, adverse event (AE) costs, and medical costs associated with health states were obtained from publicly available databases, literature, and real-world data. All costs were inflated to 2018 US dollars. Utilities for each health state and disutilities associated with AEs were obtained from the literature. Incremental costs per quality-adjusted life year (QALY) and life year (LY) gained were estimated comparing lenalidomide maintenance therapy with each comparator. Deterministic sensitivity analyses (DSAs) were performed to test the robustness of the results.Results: Over a lifetime time horizon, lenalidomide maintenance was associated with an increase of 3.64 and 2.76 in LYs compared with no treatment and bortezomib maintenance, respectively; and an increase of 2.99 and 2.42 in QALYs, respectively. Pts in the lenalidomide maintenance arm incurred higher total direct costs with an incremental cost of $476,690 and $412,872 versus no treatment and bortezomib maintenance, respectively. Initial and post-progression treatment costs comprised the majority of direct costs. The annual treatment costs for lenalidomide maintenance decreased by 49% and 86%, 3 years and 5 years after treatment initiation, respectively.Incremental cost per LY gained for lenalidomide maintenance versus no treatment and bortezomib maintenance was $130,817 and $149,411, respectively, and incremental cost per QALY gained was $159,240 and $170,408, respectively. The base-case results suggest that lenalidomide is cost-effective at a willingness-to-pay threshold of $200,000.Results from the DSA generally supported the base-case findings, with the largest variation observed when time horizon and treatment costs for lenalidomide were varied. Longer time horizons yielded greater cost-effectiveness for lenalidomide because of the reduction in treatment costs and increased effectiveness benefits. Lower initial treatment costs also yielded greater cost-effectiveness for lenalidomide.Conclusions: Over a lifetime time horizon, compared to no treatment and treatment with bortezomib, lenalidomide maintenance resulted in better effectiveness with incremental QALYs of 2.99 and 2.42, respectively, favorable incremental cost-effectiveness ratios, and an OS advantage. Annual treatment costs for lenalidomide decrease with incremental effectiveness increasing over time. Lenalidomide maintenance after ASCT offers a cost-effective strategy in the treatment of pts with NDMM from a US third-party payer perspective. DisclosuresZhou:Celgene Corporation: Research Funding; Analysis Group, Inc.: Employment. Parikh:Celgene Corporation: Employment, Equity Ownership. Chai:Celgene Corporation: Research Funding; Analysis Group, Inc.: Employment. Rokito:Analysis Group, Inc.: Employment; Celgene Corporation: Research Funding. Udeze:Celgene Corporation: Employment. Xie:Celgene Corporation: Research Funding; Analysis Group, Inc.: Employment. Agarwal:Celgene Corporation: Employment.

A cost comparison of rasburicase versus dialysis in the management of children with acute leukaemia and lymphoma at a South African centre

Background: Tumour lysis syndrome is a common complication of haematological malignancies and has historically been managed with hyperhydration, urine alkalinisation and allopurinol with renal dialysis reserved for patients in acute renal failure. Rasburicase has been shown to drastically reduce the need for dialysis; however, its use is limited in developing countries owing to its cost and availability.Aim: This retrospective analysis aimed to compare the cost to state per patient of rasburicase compared to dialysis in the management and prevention of tumour lysis syndrome in paediatric patients presenting with haematological malignancies admitted to Red Cross War Memorial Children’s Hospital (RCWMCH).Setting: Red Cross War Memorial Children’s Hospital.Methods: Patients from two consecutive 35 month periods, before and after the availability of rasburicase at RCWMCH, were grouped according to treatment modality, and the cumulative costs of hospitalisation, dialysis and drug administration were compared.Results: The groups were comparable in mean age and gender. The mean total length of hospital stay was 10.04 days shorter for the rasburicase group than the dialysis group with the average cost per patient in the rasburicase group being R40 989.64 lower than the dialysis group.Conclusion: The use of rasburicase results in a significant per patient cost saving when compared to dialysis, which often requires intensive care admission, and results in extended hospitalisation. The study supports the continued use of rasburicase as an essential adjunct in the management and prevention of tumour lysis syndrome, reaffirming its use as a cost-effective and efficient drug.