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Aims\ud \ud Accurately estimating mean survival after solid organ transplant (SOT) is crucial for efficient healthcare resource allocation decisions. However, registry-based post-transplant recipient survival estimates vary greatly and are incomplete. Often, the methods used in lifetime survival extrapolation may not fit complex transplant data and therefore alternative methods are required. We aimed to explore the flexible cubic spline methodology as a meaningful alternative for estimating lifetime survival following SOT.\ud \ud \ud \ud Methods\ud \ud Survival analyses were conducted in kidney, liver, heart, and lung transplant recipients. Mean survival was estimated using flexible cubic splines on the hazard scale fitted with three knots, based on where hazards changed direction, clinical advice, and best-fit curve using Akaike and Bayesian information criterion. The tail was extrapolated when data were no longer available. Extrapolation tails were compared with general population mortality, using age-matched life table hazards, and the highest hazards were taken at all times.\ud \ud \ud \ud Results\ud \ud We found that mean survival post-transplant was longest for kidney (US: 22.79 years; UK: 26.58 years), followed by liver (US: 20.90 years; UK: 20.38 years), heart (US: 14.82 years; UK: 15.85 years) and lung (US: 9.28 years; UK: 9.21 years). A sensitivity analysis using two knots found differences in survival ranging from −1.30 to +4.83 years across SOTs examined.\ud \ud \ud \ud Limitations\ud \ud This study does not represent individual patient survival, survival by age groups, multiple-organ transplants, or assess factors that may impact overall or organ survival.\ud \ud \ud \ud Conclusions\ud \ud Our study estimates reflect real-world survival following SOTs and demonstrate the importance of including long-term hazards in survival estimations. These lifetime survival estimates can be used by decision makers in situations where means are preferred over medians (e.g. population projections, budgetary estimates, and cost-effectiveness models) and can thus offer a meaningful alternative to the estimates used and accepted in current practice.

e19551 Background: Loncastuximab tesirine (loncastuximab tesirine-lpyl; Lonca) is an FDA approved CD19-directed antibody-drug conjugate for R/R DLBCL. From the LOTIS-2 trial primary data cut (April 6, 2020), overall response rate was 48.3% and median overall survival (OS) was 9.9 months. The OS Kaplan-Meier (KM) plot displayed a survival plateau suggesting the presence of long-term survivors (LTS). Survival analyses were conducted on a more mature data cut (March 1, 2021; median follow-up = 1.7 years, follow-up completeness at median = 81%) to estimate the percentage of LTS and expected lifetime survival (mean OS) for lonca-treated patients. Methods: Consistent with studies of other R/R DLBCL treatments, identified through a literature review, parametric and mixture cure models were fit utilizing multiple distributions. Flexible cubic spline (hazard scale 1-3 knots) and non-mixture cure analyses were also conducted. Age- and gender-matched United States life table hazards were used in projections for LTS and to ensure modeled hazards were not less than the general population. Best-fit models were determined through fit statistics, KM and fitted curve overlays, and clinical plausibility. The best-fit model from each method was a candidate for overall best fit. A hybrid model following the best-fit parametric/spline model to a defined time point and switching to general population mortality was also constructed. Results: Mixture and non-mixture cure models fit best (individual best fits gamma and Weibull, respectively). Parametric and spline models (individual best fits log-normal and 2 knot models, respectively) did not fit the observed data well nor fit the clinical expectation of long-term survival. Due to better fit, spline models were used in the hybrid model. LTS from the mixture cure and non-mixture cure models were 24-26%. Mixture cure, non-mixture cure, and hybrid model with a 2-year switch point were consistent in survival predictions (6.11-6.23 years). In a sensitivity analysis with 3-year switch point in the hybrid model, the estimated survival was shorter due to the switch point being below the observed survival plateau. Table presents full survival results and fit statistics. Conclusions: The observed survival plateau suggests lonca-treated patients may include LTS. Mixture cure, non-mixture cure, and hybrid models fit the trial data well and align on survival projections (6.11-6.23 years). Additional follow-up may help refine the switch point of the hybrid model and confirm presence of LTS.[Table: see text]

BACKGROUND: Psoriasis causes work productivity impairment that increases with disease severity. Whether differential treatment efficacy translates into differential indirect cost savings is unknown.OBJECTIVE: To assess work hours lost and indirect costs associated with secukinumab versus ustekinumab and etanercept in the United Kingdom (UK).METHODS: This was a post hoc analysis of work impairment data collected in the CLEAR study (secukinumab vs. ustekinumab) and applied to the FIXTURE study (secukinumab vs. etanercept). Weighted weekly and annual average indirect costs per patient per treatment were calculated from (i) overall work impairment derived from Work Productivity and Activity Impairment data collected in CLEAR at 16 and 52 weeks by Psoriasis Area and Severity Index (PASI) response level; (ii) weekly/annual work productivity loss by PASI response level; (iii) weekly and annual indirect costs by PASI response level, based on hours of work productivity loss; and (iv) weighted average indirect costs for each treatment. In the primary analysis, work impairment data for employed patients in CLEAR at Week 16 were used to compare secukinumab and ustekinumab. Secondary analyses were conducted at different time points and with patient cohorts, including FIXTURE.RESULTS: In CLEAR, 452 patients (67%) were employed at baseline. At Week 16, percentages of weekly work impairment/mean hours lost decreased with higher PASI: PASI < 50: 22.8%/7.60 h; PASI 50-74: 13.3%/4.45 h; PASI 75-89: 6.4%/2.14 h; PASI ≥ 90: 4.9%/1.65 h. Weighted mean weekly/annual work hours lost were significantly lower for secukinumab than ustekinumab (1.96/102.51 vs. 2.40/125.12; P = 0.0006). Results were consistent for secukinumab versus etanercept (2.29/119.67 vs. 3.59/187.17; ΡCONCLUSIONS: Secukinumab significantly reduced work impairment and associated indirect costs of psoriasis compared with ustekinumab and etanercept at Week 16 through 52 in the United Kingdom.

Objective The aim was to determine the cost effectiveness of secukinumab, a fully human interleukin-17A inhibitor, for adults in the UK with active psoriatic arthritis (PsA) who are tumour necrosis factor inhibitor (TNFi) naïve and without concomitant moderate-to-severe psoriasis, and who have responded inadequately to conventional systemic disease-modifying anti-rheumatic drugs (csDMARDs). Perspective and setting The study took the perspective and setting of the UK National Health Service (NHS). Methods The model structure was a 3-month decision tree leading into a Markov model. Separate analyses based on the number of prior csDMARDs (one and two or more) were conducted, with secukinumab 150 mg compared to standard of care (SoC) and TNFis, respectively, for each subpopulation. Clinical parameters, including response at 3 months, were from the FUTURE 2 trial and a network meta-analysis. Outcomes included total costs and quality-adjusted life years (QALYs) over the 40-year time horizon (3.5% annual discount for both outcomes; cost year 2017), and incremental cost effectiveness ratios (ICERs). Results The ICER for secukinumab 150 mg versus SoC was £28,748 per QALY gained (one prior csDMARD). Secukinumab 150 mg dominated golimumab, certolizumab pegol and etanercept, and had an ICER of £5680 per QALY gained versus adalimumab and > £1 million saved per QALY foregone versus infliximab (two or more prior csDMARDs). Valuing one QALY at between £20,000 and £30,000, the probability of secukinumab having the highest net monetary benefit was 48.9% (one prior csDMARD) and 88.9% (two or more prior csDMARDs). Parameters related to Health Assessment Questionnaire scores were most influential. Conclusions Secukinumab 150 mg at list price appears to represent a cost-effective use of NHS resources for adults with PsA who have responded inadequately to one or two or more prior csDMARDs. Electronic supplementary material The online version of this article (10.1007/s40273-018-0674-x) contains supplementary material, which is available to authorized users.

Objective: The study evaluates the cost-effectiveness of secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, vs currently licensed biologic treatments in patients with active psoriatic arthritis (PsA) from a Canadian healthcare system perspective. Methods: A decision analytic semi-Markov model evaluated the cost-effectiveness of secukinumab 150 mg and 300 mg compared to subcutaneous biologics adalimumab, certolizumab pegol, etanercept, golimumab, and ustekinumab, and intravenous biologics infliximab and infliximab biosimilar in biologic-naive and biologic-experienced patients over a lifetime horizon. The response to treatments was evaluated after 12 weeks by PsA Response Criteria (PsARC) response rates. Non-responders or patients discontinuing initial-line of biologic treatment were allowed to switch to subsequent-line biologics. Model input parameters (Psoriasis Area Severity Index [PASI], Health Assessment Questionnaire [HAQ], withdrawal rates, costs, and resource use) were collected from clinical trials, published literature, and other Canadian sources. Benefits were expressed as quality-adjusted life years (QALYs). An annual discount rate of 5% was applied to costs and benefits. The robustness of the study findings were evaluated via sensitivity analyses. Results: Biologic-naive patients treated with secukinumab achieved the highest number of QALYs (8.54) at the lowest cost (CAD 925,387) over a lifetime horizon vs all comparators. Secukinumab dominated all treatments, except for infliximab and its biosimilar, which achieved minimally more QALYs (8.58). However, infliximab and its biosimilar incurred more costs than secukinumab (infliximab: CAD 1,015,437; infliximab biosimilar: CAD 941,004), resulting in higher cost-effectiveness estimates relative to secukinumab. In the biologic-experienced population, secukinumab dominated all treatments as it generated more QALYs (8.89) at lower costs (CAD 954,692). Deterministic sensitivity analyses indicated the results were most sensitive to variation in PsARC response rates, change in HAQ, and utility values in both populations. Conclusions: Secukinumab is either dominant or cost-effective vs all licensed biologics for the treatment of active PsA in biologic-naive and biologic-experienced populations in Canada.

Introduction Dupilumab significantly improves signs and symptoms of atopic dermatitis (AD), including pruritus, symptoms of anxiety and depression, and health-related quality of life versus placebo in adults with moderate-to-severe AD. Since the cost-effectiveness of dupilumab has not been evaluated, the objective of this analysis was to estimate a value-based price range in which dupilumab would be considered cost-effective compared with supportive care (SC) for treatment of moderate-to-severe AD in an adult population. Methods A health economic model was developed to evaluate from the US payer perspective the long-term costs and benefits of dupilumab treatment administered every other week (q2w). Dupilumab q2w was compared with SC; robustness of assumptions and results were tested using sensitivity and scenario analyses. Clinical data were derived from the dupilumab LIBERTY AD SOLO trials; healthcare use and cost data were from health insurance claims histories of adult patients with AD. The annual price of maintenance therapy with dupilumab to be considered cost-effective was estimated for decision thresholds of US$100,000 and $150,000 per quality-adjusted life-year (QALY) gained. Results In the base case, the annual maintenance price for dupilumab therapy to be considered cost-effective would be $28,770 at a $100,000 per QALY gained threshold, and $39,940 at a $150,000 threshold. Results were generally robust to parameter variations in one-way and probabilistic sensitivity analyses. Conclusion Dupilumab q2w compared with SC is cost-effective for the treatment of moderate-to-severe AD in US adults at an annual price of maintenance therapy in the range of $29,000–$40,000 at the $100,000–$150,000 per QALY thresholds. Funding Sanofi and Regeneron Pharmaceuticals, Inc.

Background Antiangiogenic therapy is a proven therapeutic modality for refractory gastric and gastroesophageal junction adenocarcinoma. This trial assessed whether the addition of a high affinity angiogenesis inhibitor, ziv-aflibercept, could improve the efficacy of first-line mFOLFOX6 (oxaliplatin, leucovorin, and bolus plus infusional 5- fluorouracil) in metastatic esophagogastric adenocarcinoma. Methods Patients with treatment-naive metastatic esophagogastric adenocarcinoma were randomly assigned (in a 2:1 ratio) in a multicenter, placebo-controlled, double-blind trial to receive first-line mFOLFOX6 with or without ziv-aflibercept (4 mg/kg) every 2 weeks. The primary endpoint was 6-month progression-free survival (PFS). Results Sixty-four patients were randomized to receive mFOLFOX6 and ziv-aflibercept (43 patients) or mFOLFOX6 and a placebo (21 patients). There was no difference in the PFS, overall survival, or response rate. Patients treated with mFOLFOX6/ziv-aflibercept tended to be more likely to discontinue study treatment for reasons other than progressive disease (P = .06). The relative dose intensity of oxaliplatin and 5-fluorouracil was lower in the mFOLFOX6/ziv-aflibercept arm during the first 12 and 24 weeks of the trial. There were 2 treatment-related deaths due to cerebral hemorrhage and bowel perforation in the mFOLFOX6/ziv-aflibercept cohort. Conclusions Ziv-aflibercept did not increase the anti-tumor activity of first-line mFOLFOX6 in metastatic esophagogastric cancer, potentially because of decreased dose intensity of FOLFOX. Further evaluation of ziv-aflibercept in unselected, chemotherapy-naive patients with metastatic esophagogastric adenocarcinoma is not warranted.

Purpose In this analysis, we compared costs and explored the cost-effectiveness of subsequent-line treatment with cetuximab or panitumumab in patients with wild-type KRAS (exon 2) metastatic colorectal cancer (mCRC) after previous chemotherapy treatment failure. Data were used from ASPECCT (A Study of Panitumumab Efficacy and Safety Compared to Cetuximab in Patients With KRAS Wild-Type Metastatic Colorectal Cancer), a Phase III, head-to-head randomized noninferiority study comparing the efficacy and safety of panitumumab and cetuximab in this population. Methods A decision-analytic model was developed to perform a cost-minimization analysis and a semi-Markov model was created to evaluate the cost-effectiveness of panitumumab monotherapy versus cetuximab monotherapy in chemotherapy-resistant wild-type KRAS (exon 2) mCRC. The cost-minimization model assumed equivalent efficacy (progression-free survival) based on data from ASPECCT. The cost-effectiveness analysis was conducted with the full information (uncertainty) from ASPECCT. Both analyses were conducted from a US third-party payer perspective and calculated average anti–epidermal growth factor receptor doses from ASPECCT. Costs associated with drug acquisition, treatment administration (every 2 weeks for panitumumab, weekly for cetuximab), and incidence of infusion reactions were estimated in both models. The cost-effectiveness model also included physician visits, disease progression monitoring, best supportive care, and end-of-life costs and utility weights estimated from EuroQol 5-Dimension questionnaire responses from ASPECCT. Findings The cost-minimization model results demonstrated lower projected costs for patients who received panitumumab versus cetuximab, with a projected cost savings of $9468 (16.5%) per panitumumab-treated patient. In the cost-effectiveness model, the incremental cost per quality-adjusted life-year gained revealed panitumumab to be less costly, with marginally better outcomes than cetuximab. Implications These economic analyses comparing panitumumab and cetuximab in chemorefractory wild-type KRAS (exon 2) mCRC suggest benefits in favor of panitumumab. ClinicalTrials.gov identifier: NCT01001377.

Psoriasis is associated with a high economic burden to society. New psoriasis systemic treatments offer the potential for improved skin clearance. Whether a higher degree of clearing translates into economic benefit through decreased work impairment has not been fully determined.To assess whether more complete clearing of psoriasis is associated with a reduction in disease-related indirect costs.Pooled data from employed patients included in the CLEAR study, a phase 3b study comparing the efficacy and safety of secukinumab (337 subjects) versus ustekinumab (339 subjects), were classified into 4 levels of skin clearance improvement at weeks 16 and 52: Psoriasis Area and Severity Index (PASI) improvement from baseline of50% (PASI50), 50%-74% (PASI 50-74), 75%-89% (PASI 75-89), and ≥ 90% (PASI ≥ 90). Patients completed the Work Productivity and Activity Impairment questionnaire for psoriasis (WPAI-PSO), which assessed absenteeism, presenteeism, and a composite overall work impairment over the previous 7 days at weeks 16 and 52. U.S. Department of Labor data were used to calculate annual indirect costs due to work productivity loss.In the CLEAR study, 452 (67%) were employed at baseline and included in this analysis. At week 16, mean overall work impairment significantly decreased with higher PASI improvements: 22.8% for PASI50, compared with 13.3% for PASI 50-74 (P = 0.001); 6.4% for PASI 75-89 (P0.001); and 4.9% for PASI ≥ 90 (P0.001), with the majority of work impairment related to presenteeism. Calculated mean work hours lost by overall work impairment decreased with higher PASI improvements: 8.2 hours lost/week (429 hours/year) for patients with PASI 50; 4.6 hours lost/week (251 hours/year) for PASI 50-74; 2.3 hours lost/week (121 hours/year) for PASI 75-89; and 1.8 hours lost/week (93 hours/year) for PASI ≥ 90. Associated mean annual indirect costs due to work productivity loss per worker decreased with higher PASI improvements: $10,318 for PASI50, $6,042 for PASI 50-74, $2,901 for PASI 75-89, and $2,233 for PASI ≥ 90. Similar results were observed at week 52. Mean overall work impairment decreased with higher PASI improvements, ranging from 26.3% for PASI50 to 6.9% for PASI ≥ 90. A decrease in overall work hours lost (ranging from 9.5 hours lost/week [495 hours/year] for PASI50 to 2.5 hours/week [130 hours/year] for PASI ≥ 90), as well as associated annual indirect costs due to work productivity loss (ranging from $11,906 for PASI50 to $3,125 for PASI ≥ 90), were also shown with higher PASI improvements at week 52.Among working patients with moderate to severe psoriasis, higher PASI improvements were associated with lower work productivity loss and reduced annual indirect costs. By improving and sustaining skin clearance, psoriasis treatments may contribute to increased work productivity and decreased societal economic burden.Funding for this study was provided by Novartis Pharmaceuticals. Zhao and Herrera are employed by Novartis. Gilloteau is employed by Novartis Pharma AG. McBride, Graham, and Miles are employed by RTI Health Solutions, which provides consulting and other research services to pharmaceutical, device, governmental, and nongovernmental organizations and received funding from Novartis for manuscript development, analysis development, and general consultation. Feldman reports grants and personal fees from Novartis, Abbvie, Janssen, Lilly, and Celgene, along with personal fees from Amgen and Valeant.

Objective To determine the cost effectiveness of secukinumab, a fully human interleukin-17A inhibitor, for adults in the UK with active ankylosing spondylitis (AS) who have not responded adequately to previous treatment with conventional care (CC; biologic-naïve population) or previous biologic therapy (biologic-experienced population). Perspective and Setting UK National Health Service (NHS). Methods The model was structured as a 3-month decision tree leading into a Markov model. Comparators were licensed tumour necrosis factor inhibitors (including available biosimilars) and CC in the biologic-naïve and biologic-experienced populations, respectively. Clinical parameters captured treatment response, short-term disease activity and patient functioning, as well as long-term structural disease progression. Utilities were derived from secukinumab trial data. List prices were used for all drugs. The cost year was 2017 and costs and outcomes were discounted at 3.5%. Results In the biologic-naïve population, secukinumab dominated adalimumab and certolizumab pegol. Incremental cost-effectiveness ratios (ICERs) versus other comparators were either below £10,000 per quality-adjusted life-year (QALY) gained or south-west ICERs that implied cost effectiveness of secukinumab. In biologic-experienced patients, the ICER for secukinumab versus CC was £4927 per QALY gained. Treatment response rates, short-term treatment effects, long-term radiographic progression and biologic acquisition costs were key model drivers. Scenario analysis found results to be robust to changes in model structural assumptions. Probabilistic analysis identified greater uncertainty in results in the biologic-naïve population. Conclusions Even at list price, secukinumab appears to represent a cost-effective use of NHS resources for biologic-naïve and biologic-experienced patients with active AS. Further research on long-term radiographic progression outcomes would be valuable for future cost-effectiveness analyses in AS. Electronic supplementary material The online version of this article (10.1007/s40273-018-0675-9) contains supplementary material, which is available to authorized users.

Aim: To evaluate the cost-effectiveness of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, compared to other clinically used biologics (adalimumab, infliximab, and ustekinumab) in Japan for the treatment of moderate-to-severe psoriasis from the healthcare system (total costs) and patient co-payment (using different frequencies of drug purchase) perspectives. Methods: A decision-tree (first year)/Markov model (subsequent years), with an annual cycle, was developed. The model adopted a 5-year time horizon. Efficacy inputs were obtained from a mixed-treatment comparison analysis, and other model inputs were collected from published literature and local Japanese sources. Model outcomes included quality-adjusted life years (QALYs) and an incremental cost-effectiveness ratio (ICER) in terms of cost per QALY gained. The annual discounting rate of 2% was applied to both costs and outcomes. Results: Results for the healthcare system perspective showed that secukinumab had the highest number of quality-adjusted life years (QALYs) (4.07) vs other biologics, dominated ustekinumab and infliximab, and the ICER of secukinumab compared to adalimumab was ¥8,418,222/QALY gained. In the patient co-payment perspective with the monthly purchase of drugs, ustekinumab had the lowest co-payment cost, followed by infliximab, adalimumab, and secukinumab. In the patient co-payment perspective with a once every 3 months purchase of secukinumab and adalimumab, the co-payment costs of secukinumab, adalimumab, and ustekinumab became comparable, and infliximab had the highest co-payment cost. Limitations: Only short-term efficacy data was modeled, as there was a lack of data on long-term outcomes. Treatment sequencing was restricted to first-line biologic treatment. Drop-out rates for comparators were assumed to be equivalent to secukinumab in the absence of available data. Conclusions: Secukinumab is a cost-efficient treatment for moderate-to-severe psoriasis, providing greater health outcomes to patients at lower total costs compared to infliximab and ustekinumab, as well as comparable patient co-payment relative to other biologic treatments.

BACKGROUND Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin 17A, has demonstrated strong and sustained efficacy in adults with moderate to severe psoriasis in clinical trials. OBJECTIVE This analysis compared the cost per responder of secukinumab as first biologic treatment of moderate to severe psoriasis, with adalimumab, infliximab, etanercept and ustekinumab in Germany. METHODS A 52-week decision-tree model was developed. Response to treatment was assessed based on the likelihood of achieving a predefined Psoriasis Area and Severity Index (PASI) response to separate the cohort into responders (PASI ≥75), partial responders (PASI 50 to 74) and non-responders (PASI

To compare the costs of first-line treatment with panitumumab + FOLFOX in comparison to cetuximab + FOLFIRI among patients with wild-type (WT) RAS metastatic colorectal cancer (mCRC) in the US.A cost-minimization model was developed assuming similar treatment efficacy between both regimens. The model estimated the costs associated with drug acquisition, treatment administration frequency (every 2 weeks for panitumumab, weekly for cetuximab), and incidence of infusion reactions. Average anti-EGFR doses were calculated from the ASPECCT clinical trial, and average doses of chemotherapy regimens were based on product labels. Using the medical component of the consumer price index, adverse event costs were inflated to 2014 US dollars, and all other costs were reported in 2014 US dollars. The time horizon for the model was based on average first-line progression-free survival of a WT RAS patient, estimated from parametric survival analyses of PRIME clinical trial data.Relative to cetuximab + FOLFIRI in the first-line treatment of WT RAS mCRC, the cost-minimization model demonstrated lower projected drug acquisition, administration, and adverse event costs for patients who received panitumumab + FOLFOX. The overall cost per patient for first-line treatment was $179,219 for panitumumab + FOLFOX vs $202,344 for cetuximab + FOLFIRI, resulting in a per-patient saving of $23,125 (11.4%) in favor of panitumumab + FOLFOX.From a value perspective, the cost-minimization model supports panitumumab + FOLFOX instead of cetuximab + FOLFIRI as the preferred first-line treatment of WT RAS mCRC patients requiring systemic therapy.

Objective This study updated a 2001 decision economic model that used indirect data and confirmed its findings by developing a new cost-effectiveness model by using now available head-to-head data. The models compared olanzapine with ziprasidone in the treatment of schizophrenia in the United States. Methods A decision analytic modeling approach was used to estimate annual health-care costs and health outcomes, incorporating events such as response, relapse, and suicide. Patients without response to first-line treatment switched to the other comparator. Decision tree probabilities were extracted from head-to-head studies and other published clinical literature. Direct health-care costs and quality-adjusted life-years (QALYs) were estimated on the basis of resource use and utility weights for initial and relapse episodes, maintenance therapy, and extended episodes of illness. Disutilities associated with treatment-emergent adverse events were included. Results Consistent with the 2001 model, this model found that first-line treatment with olanzapine is associated with fewer hospital days, fewer days with extrapyramidal symptoms, and higher QALYs than is first-line treatment with ziprasidone. Total costs were lower for the olanzapine pathway ($70,232–$72,776 vs. $73,086–$73,310 in the Positive and Negative Syndrome Scale analysis) due to the cost savings associated with reduced health-care resource use. The incremental cost per QALY gained indicated that the olanzapine pathway dominated the ziprasidone pathway. Conclusions Decision analytic models should be continuously assessed against new data. This case study shows that incorporating new data confirmed results of a previously published model in which olanzapine was associated with better expected health outcomes and lower total health-care costs than was ziprasidone.

e20037Background: New treatments for relapsed/refractory multiple myeloma have recently been FDA approved in the United States (US). For FDA approval, these treatments are compared to historic stan...

e16072Background: There are limited treatment (tx) options for metastatic esophageal cancer patients (pts). We sought to determine the safety and efficacy of pembro among US pts with previously tre...

After renal transplantation, immunosuppressive regimens associated with high short-term survival rates are not necessarily associated with high long-term survival rates, suggesting that regimens may need to be optimized over time. Calcineurin inhibitor (CNI) withdrawal from a sirolimus-based immunosuppressive regimen may maximize the likelihood of long-term graft and patient survival by minimizing CNI-associated nephrotoxicity. In this study, a lifetime Markov model was created to compare the cost-effectiveness of a sirolimus-based CNI withdrawal regimen (sirolimus plus steroids) with other common CNI-containing regimens in adult de novo renal transplantation patients. Long-term graft survival was estimated by renal function and data from published studies and the US transplant registry, including short- and long-term outcomes, utility weights, and health-state costs were incorporated. Drug costs were based on average daily consumption and wholesale acquisition costs. The model suggests that treatment with sirolimus plus steroids is more efficacious and less costly than regimens consisting of a CNI, mycophenolate mofetil, and steroids; therefore, CNI withdrawal not only shows potential for long-term clinical benefits but also is expected to be cost-saving over a patient's life compared with the most commonly prescribed CNI-containing regimens.

Objective: To compare the cost-effectiveness of pegaptanib and usual care within three distinct cohorts of subfoveal neovascular age-related macular degeneration (NV-AMD) patients, that is, those with early, moderate, and late disease, using a comprehensive economic model. Methods: A Markov framework was used to model lifetime movement of a subfoveal NV-AMD cohort through health states based on visual acuity. The model takes a US payer perspective of patients over the age of 65 years. Clinical efficacy was based on published results for the 0.3 mg pegaptanib and usual care groups. Expert interviews were conducted to determine adverse event treatment patterns and vision rehabilitation resource use. Incidence and costs of comorbidities such as depression and fractures associated with the effects of declining visual acuity were based on our previously published analysis of Medicare data. Transition probabilities were derived from published clinical trial data for each 3-month cycle. Utilities were derived from published sources. Three runs of the model were conducted with cohorts of newly diagnosed patients. Patients were classified as having early, moderate, or late NV-AMD defined as visual acuity in the better-seeing eye of 20/40 to more than 20/80, 20/80 to more than 20/200, and 20/200 to more than 20/400, respectively. Costs and outcomes were discounted 3.0% per annum. Results: Incremental costs per vision-year gained and per quality-adjusted life-year (QALY) gained for early NV-AMD patients were approximately one-third those of patients with late disease ($15,279 vs. $57,230 and $36,282 vs. $132,381, respectively). On average, patients treated early with either pegaptanib or usual care incurred lower lifetime total direct costs than those treated later. Sensitivity analysis showed that base-case incremental costs per QALY gained for pegaptanib versus usual care were relatively robust. Conclusions: For patients with subfoveal NV-AMD, treatment with pegaptanib should be started as early as possible to maximize the clinical and economic benefits.

Development of inhibitors (alloantibodies to exogenous factor VIII) is the most significant treatment complication in patients with haemophilia A. The only proven way to eradicate inhibitors is through immune tolerance induction (ITI), while bypassing agents are typically employed to treat or prevent bleeds in patients with high titre inhibitors. Costs of these approaches have not been well studied. The aim of this study was to compare lifetime costs of treating patients with severe haemophilia A with inhibitors using on-demand or prophylaxis treatment with bypassing agents and ITI. A decision-analytic model was developed to compare the treatment costs and outcomes. Quantitation of the reduction in bleeding events for patients on prophylaxis and after eradication of inhibitors when on ITI and relapse of inhibitors was derived from published studies. Costs were obtained from standard US costing sources and are reported in 2014 US dollars. Costs and outcomes were discounted 3% per annum. Lifetime costs of treating patients with inhibitors are lower for ITI vs. on-demand or prophylaxis. Patients are also projected to live longer, have greater quality-adjusted life-years, and have fewer bleeding events than patients treated on-demand. Treating patients via ITI to eradicate inhibitors may result in lower lifetime costs and greater life-years and quality-adjusted life-years than treating with bypassing agents.

Background Previous economic evaluations of cinacalcet in patients with secondary hyperparathyroidism (sHPT) relied on the combination of surrogate end points in clinical trials and epidemiologic studies. Objectives The objective was to conduct an economic evaluation of cinacalcet on the basis of the EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) trial from a US payer perspective. Methods We developed a semi-Markov model to assess the cost-effectiveness of cinacalcet in addition to conventional therapy, compared with conventional therapy alone, in patients with moderate-to-severe sHPT receiving hemodialysis. We used treatment effect estimates from the unadjusted intent-to-treat (ITT) analysis and prespecified covariate-adjusted ITT analysis as our main analyses. We assessed model sensitivity to variations in individual inputs and overall decision uncertainty through probabilistic sensitivity analyses. Results The incremental cost-effectiveness ratio (ICER) for cinacalcet was $61,705 per life-year and $79,562 per quality-adjusted life-year (QALY) gained using the covariate-adjusted ITT analysis. Probabilistic sensitivity analysis suggested a 73.2% chance of the ICER being below a willingness-to-pay threshold of $100,000. Treatment effects from unadjusted ITT analysis yielded an ICER of $115,876 per QALY. The model was most sensitive to the treatment effect on mortality. Conclusions In the unadjusted ITT analysis, cinacalcet does not represent a cost- effective use of health care resources when applying a willingness-to-pay threshold of $100,000 per QALY. When using the covariate-adjusted ITT treatment effect, which represents the least biased estimate, however, cinacalcet is a cost-effective therapy for patients with moderate-to-severe sHPT on hemodialysis.

Echinocandins are recommended first-line treatment for candidaemia [1]. A cost-effectiveness model developed from a UK perspective examined costs and outcomes of antifungal treatment for candidaemia and other forms of invasive candidiasis based on European clinical guidelines [1].

4 Background: FOLFOX has RR 53% and PFS 6.8 months in MEGA (CALGB 80403). VEGF inhibition has improved survival in some but not all randomized trials in MEGA. Ziv-aflibercept binds VEGF-A, B and PlGF and has improved survival in refractory metastatic colorectal cancer. Methods: All pts received mFOLFOX6 q14d. Pts were randomized 2:1 to A) ziv-aflibercept 4mg/kg/d1 or B) placebo. Pts were restaged every 8wks. Primary endpoint: 6mos PFS. Results: 64 pts enrolled (Jan 2013-Apr 2015): sex: 55M/9F; age (median): 32-83 (62); ECOG PS 0/1/2: 33/28/3; primary tumor: esophagus 26/GEJ 18/gastric 20; measurable/evaluable: 52/12; metastases: LN 48/liver 25/lung 15, other 12/adrenal 4/bone 3. Of 64 pts: 34 POD, 9 off for tox, 4 died on tx, 3 withdrew, 4 other, 10 on tx (see Table). Conclusion: Ziv-aflibercept did not significantly improve the efficacy of FOLFOX. HTN was predictive of response to ziv-aflibercept. Except for HTN, there was no significant difference in toxicity between tx arms. Clinical trial information: NCT01747551. [Table: see text]

Men migrating to the United States from Mexico and Central America confront opposing family norms. They need to leave their families to gain family economic security; yet, leaving renders their families vulnerable. We examined the mental health implications of the opposing family norms inherent in migration using an ambivalence framework. We interviewed 60 Latino migrant farmworkers working in North Carolina. Most were from Mexico; each had left a wife and children in his country of origin. Analysis indicated that family ambivalence was common. Ambivalence was associated with anxiety symptoms (but not depression or alcohol dependence), especially among men who were unable to contact their families regularly. Results show the usefulness of the ambivalence framework, and suggest that the origins of poor migrant mental health may reside in circumstances preceding migration. Study recommendations include facilitating family contact by expanding access to telephones among migrant workers.

Studies have shown that weekly bisphosphonate dosing results in improved persistence compared to daily dosing among patients with postmenopausal osteoporosis, yet more than 50% of patients discontinue therapy within a year. An oral, less frequent administration bisphosphonate provides an opportunity to improve persistence, a parameter not well modeled in previous cost-effectiveness analyses of osteoporosis therapies.We developed a Markov model to estimate the effect of improved persistence on the cost-effectiveness of bisphosphonates among postmenopausal women with established osteoporosis (vertebral fracture and bone mineral density T-scoreor= -2.5) and an average age of 78 years. Fracture risks, clinical efficacy, mortality, resource use, costs, and utilities were obtained from the published literature. Persistence rates were derived primarily from a published clinical trial. Approximately 50% greater persistence with a monthly versus a weekly therapy was assumed on the basis of the PERSIST study, a 6-month, randomized, head-to-head prospective study that investigated treatment persistence in postmenopausal osteoporotic women on monthly versus weekly bisphosphonate therapy. Persistence was extrapolated to a maximum of 5 years. Following discontinuation, treatment benefit declined linearly and proportionally to the duration of active treatment.Based on model estimates, more fractures were avoided (versus no treatment) with monthly bisphosphonate (58.1 per 1000 treated women) than with weekly bisphosphonates (33.8 per 1000 treated women), resulting in lower fracture care costs per woman ($7317 and $7548, respectively). The incremental cost per quality-adjusted life-year gained was lower with a monthly bisphosphonate ($13,749) than with weekly bisphosphonates ($16,657) when compared to no treatment. The incremental cost per quality-adjusted life-year of a monthly bisphosphonate was $9476 when compared to a weekly bisphosphonate.In postmenopausal women with established osteoporosis, improvement in persistence with a less frequently administered oral bisphosphonate therapy could augment the fracture benefit and thereby improve cost-effectiveness. Further studies are required to refine the estimates of cost-effectiveness in order to address limited availability of adherence and fracture risk data.

4038 Background: In MEGCA, cisplatin+CAP has RR 46% and OS 12.1 mos with BEV (AVAGAST) and RR 47% and OS 13.8 mos with TRAS (ToGA). We sought to improve these results by combining CAPOX with both B...

Objective The most serious complication of treatment for patients with severe hemophilia A is the development of FVIII alloantibody inhibitors. Treating hemophilia is expensive at best; however, incurring an inhibitor substantially increases those costs. As a result, a cost-efficient strategy for treating patients with inhibitors is desirable. Three approaches have been used to treat patients with inhibitors: 1) administer bypassing agents such as activated prothrombin complex concentrate (aPCC) or activated recombinant factor VII (rFVIIa) only when a bleed occurs (on-demand); 2) administer bypassing agents prophylactically to prevent bleeds from occurring; or 3) initiate immune tolerance induction (ITI) with factor VIII (FVIII) concentrate in an attempt to eradicate the inhibitor and then long term follow up with a lower dose prophylaxis regimen to maintain the inhibitor free status. In this study, we compare the costs and outcomes of these treatment strategies in order to assist healthcare providers in making more informed treatment decisions. Methods A decision-analytic model (Figure 1) was developed to compare commonly used treatment regimens for severe hemophilia A patients with inhibitors over the course of an average patient's lifetime. On-demand patients were treated for their acute bleeding events with a conventional dose of rFVIIa (based on the FENOC study, a mean of 105 µg/kg) administered every 2-3 hours until the bleed stopped. Patients treated prophylactically received 85 IU/kg of aPCC 3 times per week (from Pro-FEIBA study). The International Immune Tolerance Study compared ITI treatment with either a low dose (50 IU/kg 3 times a week) or a high-dose regimen (200 IU/kg daily) of FVIII concentrate. The high dose regimen was selected for inclusion in this decision-analytic model due to its more rapid induction of immune tolerance with fewer break-through bleeds. When ITI was successful, FVIII replacement dosing was resumed at a prophylactic level (30 IU/kg FVIII 3 times per week). Data from the International and North American ITI Registries were used to estimate the success of inhibitor eradication on ITI. Relapse of inhibitors was assumed to occur in 15% of patients 15 years after inhibitors had been eradicated. Patients who failed primary and secondary ITI or who succeeded and then relapsed were treated prophylactically with bypassing agents (85 IU/kg of aPCC 3 times per week). The rate of reduced bleeding events for patients on prophylaxis was derived from the results observed in previously published clinical studies. The lifetime projections of product dosing requirement considered changes in patient weight over time. Life expectancy was modeled via US life tables and an increased risk of death was ascribed to the presence of inhibitors (as per CDC data reported by Soucie). Costs were obtained from standard US costing sources and are reported in 2013 US dollars. Hemophilia-specific utility weights were estimated from the published literature. Costs and outcomes were discounted at 3% per annum. Results Treating patients with inhibitors via an ITI approach can successfully eradicate the inhibitors 74% of the time. Based on the model, the estimated lifetime costs of treating patients with inhibitors was substantially lower for the ITI approach compared with either treating on-demand or prophylactically with bypassing agents (discounted costs of $22,201,832 versus $38,656,756 and $42,104,865, respectively). In addition, patients treated via ITI are projected to live longer (74.3 years versus 69.6 and 69.6 years, respectively) and have greater discounted quality-adjusted life years (25.1 versus 14.7 and 20.5, respectively). Patients treated via ITI or prophylactically with bypassing agents incur less than half the number of bleeding events over their lifetime compared to patients treated via on-demand therapy (801 and 694 versus 1,819 bleeding events). Conclusion Treating patients via ITI in an attempt to eradicate inhibitors results in lower lifetime costs and a greater number of life years and quality-adjusted life years than when treating on-demand or prophylactically with bypassing agents. Disclosures: Earnshaw: RTI Health Solutions: Employment, Grifols has contracted RTI-HS to do research Other, Research Funding. McDade:Grifols: Research Funding. Spears:Grifols Inc: Employment. Kessler:Baxter: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Grifols: Consultancy, Research Funding; Biogen-Idec: Consultancy; Octapharma: Consultancy, Research Funding; NovoNordisk: Consultancy, Research Funding; Pfizer: Consultancy.

263 Background: The PRONOUNCE trial was a phase III, randomized, open-label U.S. study comparing pemetrexed (PemC) with bevacizumab (PCB) in the treatment of advanced chemo-naive nonsquamous non-small cell lung cancer (NS-NSCLC). The primary endpoint of improved PFS without grade 4 toxicity for PemC over PCB was not met. There were no differences in PFS or OS. This analysis was conducted to estimate differences in costs of treatment and related patient care between the groups to inform evidence-based treatment decision making. Methods: A cost-minimization analysis was performed using data from the PRONOUNCE trial and publically available U.S. unit costs. Drug costs modeled included induction, maintenance, and subsequent therapies. Other estimated medical costs were drug administration, concomitant medications, and treatment of grade 3/4 toxicities. A probabilistic sensitivity analysis (PSA) was conducted to model joint uncertainty associated with model parameters. Results: The average cost of treatment with PemC was $4,689 less than PCB ($30,334 vs $35,024). Drug acquisition and administration costs were less in all modeled settings (induction, maintenance, and subsequent lines) for PemC. Costs associated with concomitant medications and grade 3/4 toxicities were similar ($13,286 vs $13,738). PemC was cost saving in 99% of 10,000 PSA iterations. Conclusions: Based on the PRONOUNCE trial and model results, PemC may present a similarly effective but less costly treatment option for patients in the United States compared with PCB. While treatment decision making should consider the overall safety profile and patient preferences, this study provides estimates of the costs of treatment of these two therapeutic options. The analysis was based on clinical trial data; therefore, the results may not be generalizable to all patients. [Table: see text]

Objective To investigate the cost-effectiveness of panitumumab plus mFOLFOX6 (oxaliplatin, 5-fluorouracil and leucovorin) compared with bevacizumab plus mFOLFOX6 in first-line treatment of patients with wild-type RAS metastatic colorectal cancer (mCRC). Design A semi-Markov model was constructed from a French health collective perspective, with health states related to first-line treatment (progression-free), disease progression with and without subsequent active treatment, resection of metastases, disease-free after successful resection and death. Methods Parametric survival analyses of patient-level progression-free and overall survival data from the only head-to-head clinical trial of panitumumab and bevacizumab (PEAK) were performed to estimate transitions to disease progression and death. Additional data from PEAK informed the amount of each drug consumed, duration of therapy, subsequent therapy use, and toxicities related to mCRC treatment. Literature and French public data sources were used to estimate unit costs associated with treatment and duration of subsequent active therapies. Utility weights were calculated from patient-level data from panitumumab trials in the first-, second- and third-line settings. A life-time perspective was applied. Scenario, one-way, and probabilistic sensitivity analyses were performed. Results Based on a head-to-head clinical trial that demonstrates better efficacy outcomes for patients with wild-type RAS mCRC who receive panitumumab plus mFOLFOX6 versus bevacizumab plus mFOLFOX6, the incremental cost per life-year gained was estimated to be €26,918, and the incremental cost per quality-adjusted life year (QALY) gained was estimated to be €36,577. Sensitivity analyses indicate the model is robust to alternative parameters and assumptions. Conclusions The incremental cost per QALY gained indicates that panitumumab plus mFOLFOX6 represents good value for money in comparison to bevacizumab plus mFOLFOX6 and, with a willingness-to-pay ranging from €40,000 to €60,000, can be considered cost-effective in first-line treatment of patients with wild-type RAS mCRC.

Introduction Health technology assessment is not required for regulatory submission or approval in either the United States (US) or Japan. This study was designed as a cross-country evaluation of cost analyses conducted in the US and Japan based on the PRONOUNCE phase III lung cancer trial, which compared pemetrexed plus carboplatin followed by pemetrexed (PemC) versus paclitaxel plus carboplatin plus bevacizumab followed by bevacizumab (PCB). Methods Two cost analyses were conducted in accordance with International Society For Pharmacoeconomics and Outcomes Research good research practice standards. Costs were obtained based on local pricing structures; outcomes were considered equivalent based on the PRONOUNCE trial results. Other inputs were included from the trial data (e.g., toxicity rates) or from local practice sources (e.g., toxicity management). The models were compared across key input and transferability factors. Results Despite differences in local input data, both models demonstrated a similar direction, with the cost of PemC being consistently lower than the cost of PCB. The variation in individual input parameters did affect some of the specific categories, such as toxicity, and impacted sensitivity analyses, with the cost differential between comparators being greater in Japan than in the US. Conclusion When economic models are based on clinical trial data, many inputs and outcomes are held consistent. The alterable inputs were not in and of themselves large enough to significantly impact the results between countries, which were directionally consistent with greater variation seen in sensitivity analyses. The factors that vary across jurisdictions, even when minor, can have an impact on trial-based economic analyses. Funding Eli Lilly and Company. Electronic supplementary material The online version of this article (doi:10.1007/s12325-015-0270-9) contains supplementary material, which is available to authorized users.