Budget Impact of Dabrafenib and Trametinib in Combination as Adjuvant Treatment of BRAF V600E/K Mutation-Positive Melanoma from a U.S. Commercial Payer Perspective.

BACKGROUND: Before the approval of dabrafenib and trametinib in combination, there were no approved therapies in the adjuvant setting that target the RAS/RAF/MEK/ERK pathway. OBJECTIVE: To evaluate the budget impact of dabrafenib and trametinib in combination for adjuvant treatment of patients with BRAF V600 mutation-positive resected Stage IIIA, IIIB, or IIIC melanoma from a U.S. commercial payer perspective using data from the COMBI-AD trial, as well as other sources. METHODS: The budget impact of dabrafenib and trametinib in combination for patients with BRAF V600E/K mutation-positive, resected Stage IIIA, IIIB, or IIIC melanoma was evaluated from the perspective of a hypothetical population of 1 million members with demographic characteristics consistent with those of a commercially insured U.S. insurance plan (i.e., adults aged less than 65 years) using an economic model developed in Microsoft Excel. The model compared melanoma-related health care costs over a 3-year projection period under 2 scenarios: (1) a reference scenario in which dabrafenib and trametinib are assumed to be unavailable for adjuvant therapy and (2) a new scenario in which the combination is assumed to be available. Treatments potentially displaced by dabrafenib and trametinib were assumed to include observation, high-dose interferon alpha-2b, ipilimumab, and nivolumab. Costs considered in the model include those of adjuvant therapies and treatment of locoregional and distant recurrences. The numbers of patients eligible for treatment with dabrafenib and trametinib were based on data from cancer registries, published sources, and assumptions. Treatment mixes under the reference and new scenarios were based on market research data, clinical expert opinion, and assumptions. Probabilities of recurrence and death were based on data from the COMBI-AD trial and an indirect treatment comparison. Medication costs were based on wholesale acquisition cost prices. Costs of distant recurrence were from a health insurance claims study. RESULTS: In a hypothetical population of 1 million commercially insured members, 48 patients were estimated to become eligible for treatment with dabrafenib and trametinib in combination over the 3-year projection period; in the new scenario, 10 patients were projected to receive such treatment. Cumulative costs of melanoma-related care were estimated to be $6.3 million in the reference scenario and $6.9 million in the new scenario. The budget impact of dabrafenib and trametinib in combination was an increase of $549 thousand overall and 1.5 cents per member per month. CONCLUSIONS: For a hypothetical U.S. commercial health plan of 1 million members, the budget impact of dabrafenib and trametinib in combination as adjuvant treatment for melanoma is likely to be relatively modest and within the range of published estimates for oncology therapies. These results may assist payers in making coverage decisions regarding the use of adjuvant dabrafenib and trametinib in melanoma. DISCLOSURES: Funding for this research was provided to Policy Analysis Inc. (PAI) by Novartis Pharmaceuticals. Stellato, Moynahan, and Delea are employed by PAI. Ndife, Koruth, Mishra, and Gunda are employed by Novartis. Ghate was employed by Novartis at the time of this study and is shareholder in Novartis, Provectus Biopharmaceuticals, and Mannkind Corporation. Gerbasi was employed by PAI at the time of this study and is currently an employee, and stockholder, of Sage Therapeutics. Delea reports grant funding from Merck and research funding from Amgen, Novartis, Sanofi, Seattle Genetics, Takeda, Jazz, EMD Serono, and 21st Century Oncology, unrelated to this work.

Cost-effectiveness of dabrafenib and trametinib in combination as adjuvant treatment of BRAF V600E/K mutation-positive melanoma from a US healthcare payer perspective.

Objective: The COMBI-AD trial demonstrated the efficacy and safety of dabrafenib and trametinib in combination vs placebo as adjuvant treatment of patients with BRAF V600E/K mutation-positive resected Stage IIIA (lymph node metastasis >1 mm), IIIB, or IIIC melanoma. This analysis evaluated the cost-effectiveness of dabrafenib and trametinib vs observation from a US healthcare payer perspective.Methods: This evaluation employed a non-homogeneous, semi-Markov, cohort model with health states for relapse-free survival (RFS), post-locoregional recurrence (LR), post-distant recurrence (DR) receiving first-line treatment, and post-DR receiving second-line treatment. A 50-year modeling time horizon was used. Transition probabilities were estimated based on individual patient data (IPD) from the COMBI-AD trial. Health-state utilities were estimated using EuroQol (EQ-5D) index values from COMBI-AD and published sources. Direct medical costs associated with treatment of melanoma were considered, including costs of BRAF mutation testing, medication and administration costs for adjuvant and metastatic treatments, costs of treating recurrence, and costs of adverse events. Costs and quality-adjusted life-years (QALYs) were discounted at 3.0% annually.Results: Compared with observation, adjuvant dabrafenib and trametinib was estimated to result in a gain of 2.15 QALYs at an incremental cost of $74,518. The incremental cost-effectiveness ratio (ICER) was estimated to be $34,689 per QALY. In deterministic sensitivity analyses, the ICER was sensitive to the cost of dabrafenib and trametinib and the distribution used for projecting RFS beyond the end of follow-up in the COMBI-AD trial. At a cost-effectiveness threshold of $100,000 per QALY, the probability that dabrafenib and trametinib is cost-effective was estimated to be 92%.Conclusions: Given generally-accepted cost-effectiveness threshold values in the US, dabrafenib plus trametinib is likely to be a cost-effective adjuvant therapy for patients with BRAF mutation positive melanoma. These results may be useful for policy-makers in their deliberations regarding reimbursement and access to this treatment.

Cost-Effectiveness of Secukinumab Versus Other Biologics in the Treatment of Psoriatic Arthritis: An Argentinean Perspective.

OBJECTIVE: Psoriatic arthritis (PsA) is a chronic, systemic inflammatory disease. This study assessed the cost-effectiveness of secukinumab, an interleukin-17A inhibitor, versus other biologics in PsA from the Argentinean social security perspective. METHODS: A semi-Markov model evaluated subcutaneous (sc) treatment with secukinumab 150 mg and 300 mg against other sc treatments such as adalimumab, certolizumab pegol, etanercept, golimumab, ustekinumab, and intravenous treatment infliximab in biologic-naïve (with or without moderate to severe psoriasis) and biologic-experienced PsA patients over a lifetime horizon. Response to treatments was determined using the PsA Response Criteria (PsARC) at 12 weeks. Model inputs were derived from randomized controlled trials, network meta-analyses, published literature, and other Argentinean sources. Model outcomes included quality-adjusted life years (QALYs) gained and incremental cost-effectiveness ratios. Sensitivity analyses and alternative scenarios with a higher cost option were also conducted. RESULTS: Among biologic-naïve PsA patients without psoriasis, secukinumab 150 mg provided the highest QALYs (7.18) versus all sc biologics at the lowest cost ($3 755 678 Argentine peso), thus dominating them. Among biologic-naïve PsA patients with psoriasis and biologic-experienced PsA patients, secukinumab 300 mg provided highest QALYs (6.99 and 7.53, respectively), dominated infliximab, and was cost-effective versus other sc biologics. Deterministic sensitivity analyses indicated sensitivity of results to variation in PsARC rates, drug acquisition costs, Health Assessment Questionnaire change, and utilities. A probabilistic sensitivity analysis showed maximum net monetary benefits with both secukinumab doses. Results from an alternative scenario analysis were similar to base-case analysis. CONCLUSIONS: For both biologic-naïve and experienced PsA patients, secukinumab is either a dominant or cost-effective treatment option compared with other biologics in Argentina.

Cost-effectiveness of secukinumab compared to other biologics in the treatment of ankylosing spondylitis in Finland.

AIM: This study assesses the cost-effectiveness of secukinumab vs currently licensed biologics for the treatment of ankylosing spondylitis (AS) from the Finnish health care system perspective. METHODS: A semi-Markov model compared secukinumab with adalimumab, adalimumab biosimilar, certolizumab pegol, etanercept, etanercept biosimilar, golimumab, and infliximab in a biologic-naïve population over a lifetime horizon. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used to assess the treatment response. Efficacy inputs were obtained from the network meta-analysis, and other model inputs were obtained from the published literature and Finnish sources. Main study outcomes included quality-adjusted life years (QALYs) gained and incremental cost-effectiveness ratio in terms of cost per QALY gained. Robustness of results was confirmed by sensitivity analyses and alternative scenario analyses. RESULTS: Secukinumab achieved highest QALYs (13.1) at lowest expected lifetime cost (€279,872) vs other comparators in biologic-naïve AS patients in the base case analysis, thus it dominated other biologics. Golimumab had a second highest QALYs (12.9) at the total cost of €309,551. Results were sensitive to variation in BASDAI 50 response for secukinumab, baseline Bath Ankylosing Spondylitis Functional Index (BASFI) score across all drugs, change in BASDAI and BASFI scores, and discount rates as observed in the one-way sensitivity analyses. Secukinumab was either dominant or cost-effective treatment in different alternative scenarios. CONCLUSION: Secukinumab presented itself to be the dominant (ie, less costly and more effective) treatment vs other comparators for the biologic-naïve patients with AS in Finland.

Cost-effectiveness analysis of secukinumab in ankylosing spondylitis from the Canadian perspective.

AIM: To assess the cost-effectiveness of interleukin (IL)-17A inhibitor secukinumab vs the currently licensed biologic therapies in ankylosing spondylitis (AS) patients from a Canadian healthcare system perspective. METHODS: A decision analytic model (semi-Markov) evaluated the cost-effectiveness of secukinumab 150 mg compared to certolizumab pegol, adalimumab, golimumab, etanercept and etanercept biosimilar, and infliximab and infliximab biosimilar in a biologic-naïve population, over 60 years of time horizon (lifetime). The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50) response rate was used to assess treatment response at week 12. Non-responders or patients discontinuing initial-line of biologic therapy were allowed to switch to subsequent-line biologics. Model input parameters (short-term and long-term changes in BASDAI and Bath Ankylosing Spondylitis Functional Index [BASFI], withdrawal rates, adverse events, costs, resource use, utilities, and disutilities) were obtained from clinical trials, published literature, and other Canadian sources. Benefits were expressed as quality-adjusted life years (QALYs). Cost and benefits were discounted with an annual discount rate of 1.5% for all treatments. RESULTS: In the biologic-naïve population, secukinumab 150 mg dominated all comparators, as patients treated with secukinumab 150 mg achieved the highest QALYs (16.46) at the lowest cost (CAD 533,010) over a lifetime horizon vs comparators. In the deterministic sensitivity analysis, results were most sensitive to changes in baseline BASFI non-responders, BASDAI 50 at 3 months and discount rates. Probabilistic sensitivity analysis showed that secukinumab 150 mg demonstrated higher probability of achieving maximum net monetary benefit vs all comparators at various cost thresholds. CONCLUSIONS: This analysis demonstrates that secukinumab 150 mg is the most cost-effective treatment option for biologic-naïve AS patients compared to certolizumab pegol, adalimumab, golimumab, etanercept and etanercept biosimilar, and infliximab and infliximab biosimilar for a lifetime horizon in Canada. Treatment with secukinumab translates into substantial benefits for patients and the healthcare system.

Budget impact model of secukinumab for the treatment of moderate-to-severe psoriasis, psoriatic arthritis, and ankylosing spondylitis in Italy: a cross-indication initiative.

OBJECTIVE: Secukinumab, a fully human monoclonal IgG1 antibody that selectively neutralizes the proinflammatory cytokine IL-17A, has been approved in Europe in 2015 for the treatment of adult patients with moderate-to-severe plaque psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis (AS). This analysis assessed the budget impact of introduction of secukinumab to the Italian market for all three indications from the perspective of the Italian National Health Service. MATERIALS AND METHODS: A cross-indication budget impact model was developed and included biologic-treated adult patients diagnosed with psoriasis, PsA, and AS. The analyses were conducted over a 3-year time horizon and included direct costs (drug therapy costs, administration costs, diseases-related costs, and adverse events costs). Model input parameters (epidemiology, market share projections, resource use, and costs) were obtained from the published literature and other Italian sources. The robustness of the results was tested via one-way sensitivity analyses: secukinumab cost, secukinumab market share, intravenous administration costs, and adverse events costs were varied by ±10%. RESULTS: The total patient population for secukinumab over the 3-year timeframe was projected to be 6,648 in the first year, increasing to 12,001 in the third year, for all three indications combined (psoriasis, PsA, and AS). Compared to a scenario without secukinumab in the market, the introduction of secukinumab in the market for the treatment of psoriasis, PsA, and AS showed a cumulative 3-year incremental budget impact of -5%, corresponding to savings of €66.1 million and per patient savings of about €1,855. The majority of the cost savings came from the adoption of secukinumab in AS (58%), followed by PsA (29%) and psoriasis (13%). Sensitivity analyses confirmed the robustness of the results. CONCLUSION: Results from this cross-indication budget impact model show that secukinumab is a cost-saving option for the treatment of PsA, AS, and psoriasis patients in Italy.

Cost Effectiveness of Secukinumab for the Treatment of Active Ankylosing Spondylitis in the UK.

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.

Cost Effectiveness of Secukinumab for the Treatment of Active Psoriatic Arthritis in the UK.

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.

Cost-effectiveness analysis of secukinumab for the treatment of active psoriatic arthritis: a Canadian perspective.

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.

Economic Evaluation of Tobramycin Inhalation Powder for the Treatment of Chronic Pulmonary Pseudomonas aeruginosa Infection in Patients with Cystic Fibrosis.

BACKGROUND: Chronic lung infection with Pseudomonas aeruginosa occurs in approximately 50% of patients with cystic fibrosis (CF). This infection further compromises lung function, and significantly contributes to the increased healthcare costs. OBJECTIVES: Inhaled tobramycin, used to manage P. aeruginosa infection in CF patients, is available as powder (tobramycin inhalation powder, TIP) and solution (tobramycin inhalation solution, TIS). Evidence suggests increased adherence with the use of TIP over TIS. Hence, this analysis aimed to evaluate the potential pharmacoeconomic benefit of increased adherence with TIP over TIS in the US setting. METHODS: A patient-level simulation model was developed to compare TIP with TIS. Both costs and benefits were predicted over a 10-year time horizon from a payer's perspective, and were discounted annually at 3%. All costs were presented in 2016 US dollars. RESULTS: TIP was associated with greater quality-adjusted life-years (by 0.27) and lower total costs (by US$36,168) as compared with TIS over a 10-year time horizon. TIP-treated patients experienced a decreased mean number of exacerbations than TIS-treated patients (39.24 vs 50.20). Furthermore, administration of TIP via the T-326 Inhaler was associated with significant cost savings per patient, because of the nebulizer required for administering TIS (by US$1596) and exacerbation costs (by US$76,531). Probabilistic sensitivity analysis showed that TIP was dominant over TIS in 100% of the simulations. CONCLUSION: TIP is likely to be a more cost-effective treatment than TIS, and therefore may reduce the economic burden of CF.