The fiscal consequences of public health investments in disease-modifying therapies for the treatment of multiple sclerosis in Sweden.

Background and aims: The economic consequences of multiple sclerosis (MS) are broader than those observed within the health system. The progressive nature suggests that people will not be able to live a normal productive life and will gradually require public benefits to maintain living standards. This study investigates the public economic impact of MS and how investments in disease-modifying therapies (DMTs) influence the lifetime costs to government attributed to changes in lifetime tax revenue and disability benefits based on improved health status linked to delayed disease progression.Methods: Disease progression rates from previous MS Markov cohort models were applied to interferon beta-1a, peginterferon beta-1a, dimethyl fumarate, and natalizumab using a public economic framework. The established relationship between expanded disability status scale and work-force participation, annual earnings, and disability rates for each DMT were applied. Subsequently, we assessed the effect of DMTs on discounted governmental costs consisting of health service costs, social insurance and disability costs, and changes in lifetime tax revenues.Results: Fiscal benefits attributed to informal care and community services savings for interferon beta-1a, peginterferon beta-1a, dimethyl fumarate, and natalizumab were SEK340,387, SEK486,837, SEK257,330, and SEK958,852 compared to placebo, respectively. Tax revenue gains linked to changes in lifetime productivity for interferon beta-1a, peginterferon beta-1a, dimethyl fumarate, and natalizumab were estimated to be SEK27,474, SEK39,659, SEK21,661, and SEK75,809, with combined fiscal benefits of cost savings and tax revenue increases of SEK410,039, SEK596,592, SEK326,939, and SEK1,208,023, respectively.Conclusion: The analysis described here illustrates the broader public economic benefits for government attributed to changes in disease status. The lifetime social insurance transfer costs were highest in non-treated patients, and lower social insurance costs were demonstrated with DMTs. These findings suggest that focusing cost-effectiveness analysis only on health costs will likely underestimate the value of DMTs.

The Impact of Price Reductions After Loss of Exclusivity in a Cost-Effectiveness Analysis: Fingolimod Versus Interferon Beta-1a for the Treatment of Relapsing-Remitting Multiple Sclerosis.

BACKGROUND: Cost-effectiveness analyses tend not to take into account the availability of lower-priced generics following loss of exclusivity (LOE) of branded products. By not considering these generics, which are typically adopted quickly, total costs are likely to be overestimated and may be unreflective of real-world payer conditions in the United States. OBJECTIVE: To assess the impact of including future price reductions following LOE on the cost-effectiveness of fingolimod versus intramuscularly administered interferon beta-1a (IM IFNß-1a) as treatments for multiple sclerosis. METHODS: This model was adopted from a previously published Markov model and was conducted from a U.S. payer perspective over a 10-year time horizon. Patients with relapsing-remitting multiple sclerosis entered the model and received either fingolimod (an oral therapy) or IM IFNß-1a (an injectable). These treatments reflect the interventions studied in the TRANSFORMS randomized clinical trial. Clinical, cost, and utility inputs were based on a recent cost-effectiveness review of therapies for multiple sclerosis. To model LOE, price reductions and the proportion of patients switching to generic versions following LOE were based on published estimates. Price reductions varied to reflect the difference in product types (oral vs. large molecule injectable). Assumptions were also made around the proportion of patients switching to generic versions over time following LOE and the projected date of LOE. Outcomes included per-patient total direct costs (medication, administration and monitoring, and disease-related costs including relapses), quality-adjusted life-years, and the incremental cost per quality-adjusted life-year. RESULTS: Assuming no price reductions following LOE, fingolimod was considered cost-effective versus IM IFNß-1a ($118,434 per quality-adjusted life-year), despite having higher total direct costs over 10 years ($475,740 vs. $446,792). When including future price reductions following LOE, total direct costs were reduced with fingolimod and were lower than those accrued with IM IFNß-1a over the model time horizon ($308,570 vs. $442,653). Cost-effectiveness results were sensitive to changes in both clinical parameters and medication costs. Scenario analyses demonstrated that an earlier date of LOE was associated with lower total costs. CONCLUSIONS: Health economic models may predict higher total costs when the price reductions following LOE are not considered. Here, oral fingolimod was seen to be cost-saving versus IM IFNß-1a over the model time horizon when such price reductions were included. The cost implications of not accounting for future price changes may determine whether an intervention is considered cost-effective and as such may influence reimbursement decisions based on cost-effectiveness thresholds. Multiple product types (e.g., oral, injectable, and infused agents) have been approved for use as treatments for multiple sclerosis in the United States, and LOE is likely to have a different effect on each of these therapies. DISCLOSURES: This study was funded by Novartis Pharmaceuticals Corporation. Hua and Hersh report consulting fees from Novartis for work on this study. Hua also reports speaking, advisory board, and consulting fees from Biogen, Genzyme, Teva, EMD Serono, Genentech, TG Therapeutics, and Novartis for activities outside of this study. Hersh also reports speaking and consulting fees from Novartis, Biogen, Genzyme, Genentech, and EMD Serono for activities outside of this study, and research grants from PCORI and Biogen. At the time of this research, Morten and Kusel were paid employees of Costello Medical, which was contracted by Novartis to undertake some of this study's work. Lin, Cave, Herrera, and Ko were paid employees of Novartis at the time of this research. Cave, Herrera, and Ko also report owning stock in Novartis Pharmaceuticals. Varga provided services to Novartis at the time of this research and has nothing further to disclose. This research was presented as a poster at the AMCP Managed Care & Specialty Pharmacy Annual Meeting 2017; March 27-30, 2017; Denver, CO.

Incremental net monetary benefit of ocrelizumab relative to subcutaneous interferon ß-1a.

AIM: Disease-modifying therapies (DMTs) impact the natural history of relapsing forms of multiple sclerosis (RRMS) by reducing annual relapse rates and slowing disability progression. The effect of DMTs on indirect costs has not been consistently explored in cost-effectiveness studies thus far. The value to patients of an emerging DMT, ocrelizumab, was quantified in comparison to subcutaneous interferon beta-1a (IFNßSC) for the prevalent RRMS population with mild-to-moderate disability in the US, based on two Phase 3 trials, OPERA I and OPERA II, of ocrelizumab vs IFNßSC in RRMS. MATERIALS AND METHODS: A Markov model was developed to compare disability progression as measured by Expanded Disability Status Scale (EDSS) and relapse outcomes over a 30-year horizon for ocrelizumab vs IFNßSC. Direct, indirect, and informal costs (2016 US dollars) and utilities for EDSS health states were obtained from the literature. Hazard ratios for disability progression and relapse rates were estimated from clinical trials. Value was assessed by calculating the net monetary benefit (NMB), defined as the monetary value of discounted quality-adjusted life years (QALYs) minus total costs, where the value of a QALY was $150,000. One-way sensitivity analyses were conducted. RESULTS: Ocrelizumab was associated with an incremental gain of 0.84 QALYs and cost savings of $287,713 relative to IFNßSC, resulting in an incremental NMB (INMB) of $413,611 per person over 30 years. The INMB increased by $151,763 for those initiating ocrelizumab at EDSS level 1 vs level 4. Influential parameters were QALY value, treatment costs, and disability progression; however, all sensitivity analyses indicated that the INMB for ocrelizumab relative to IFNßSC was ≥$300,000 per person. CONCLUSIONS: Ocrelizumab provides greater value to RRMS patients compared with IFNßSC. Initiating ocrelizumab at lower EDSS levels leads to a greater cumulative value due to slower disability progression, which extends years with higher quality-of-life.

Cost-effectiveness of different strategies for treatment relapsing-remitting multiple sclerosis.

AIM: To compare the cost-effectiveness of different disease-modifying therapies' strategies for treatment of relapsing-remitting multiple sclerosis. METHODS: A Markov model was developed to assess the cost-effectiveness and incremental cost-effectiveness ratios for different strategies of using disease-modifying therapies from a US third-party payer perspective. All costs were converted to 2014 US$. RESULTS: Over 20 years, the total costs per patient were estimated at US$161,136.60 for Strategy 1 (symptom management [SM] alone), US$551,650.66 for Strategy 2 (SM and IFN-ß-1a), US$703,463.60 for Strategy 3 (SM and natalizumab) and US$670,985.24 for Strategy 4 (SM and alemtuzumab). The accumulated quality-adjusted life years were 10.49, 10.66, 10.69 and 10.71 for each of the four Strategies 1-4, respectively. The resulting incremental cost-effectiveness ratios were 2,297,141.53 comparing Strategy 2 to Strategy 1, and -1,623,918.00 comparing Strategy 4 to Strategy 3. CONCLUSION: Strategy 1 was the cost-effective strategy for treatment of relapsing-remitting multiple sclerosis when compared with other strategies.

Cost-effectiveness analysis of ocrelizumab versus subcutaneous interferon beta-1a for the treatment of relapsing multiple sclerosis.

AIM: To conduct a cost-effectiveness analysis to compare ocrelizumab vs subcutaneous (SC) interferon beta-1a for the treatment of relapsing multiple sclerosis (RMS). METHODS: A Markov cohort model with a 20-year horizon was developed to compare ocrelizumab with SC interferon beta-1a from a US payer perspective. A cohort of patients with relapsing-remitting MS (RRMS) and Expanded Disability Status Scale (EDSS) scores of 0-6, who initiated treatment with ocrelizumab or SC interferon beta-1a, were entered into the model. The model considered 21 health states: EDSS 0-9 in RRMS, EDSS 0-9 in secondary-progressive multiple sclerosis (SPMS), and death. Patients with RRMS could transition across EDSS scores, progress to SPMS, experience relapses, or die. Transition probabilities within RRMS while patients received ocrelizumab or SC interferon beta-1a were based on data from the two SC interferon beta-1a-controlled Phase III OPERA I and OPERA II trials of ocrelizumab in RMS. Transitions within RRMS when off-treatment, RRMS-to-SPMS transitions, transitions within SPMS, and transitions to death were based on the literature. Utilities of health states, disutilities of relapses, costs of therapies, and medical costs associated with health states, relapse, and adverse events were from the literature and publicly available data sources. The model estimated per-patient total costs, incremental cost per life year (LY) gained, and incremental cost per quality-adjusted LY (QALY) gained. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analysis (PSA) were conducted to evaluate the robustness of the model results. RESULTS: Ocrelizumab was associated with a cost savings of $63,822 and longer LYs (Δ = 0.046) and QALYs (Δ = 0.556) over a 20-year time horizon. The results of the model were robust in the DSA and PSA. LIMITATIONS: The model did not consider subsequent treatments and their impact on disease progression. CONCLUSIONS: The results suggest that ocrelizumab is more cost-effective than SC interferon beta-1a for the treatment of RMS.

Cost-Effectiveness of Peginterferon Beta-1a and Alemtuzumab in Relapsing-Remitting Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, affecting 2.5 million people globally and 400,000 people in the United States. While no cure exists for MS, the goal is to manage the disease using disease-modifying therapies (DMTs), which have been shown to slow disease progression and prevent relapses. Relapsing-remitting MS (RRMS) is the most common form of MS at the time of diagnosis. Peginterferon beta-1a (PEG) and alemtuzumab (ALT) were recently approved and have demonstrated good clinical outcomes, including reduced relapse rates in clinical trials. High costs associated with these DMTs necessitates cost-effectiveness analyses to understand their overall value in RRMS management. OBJECTIVES: To assess the cost-effectiveness of (a) Model 1: PEG relative to intramuscular interferon beta-1a (IM IFN), subcutaneous interferon beta-1b (SC IFN), glatiramer acetate 20 mg per mL (GA), fingolimod (FIN), natalizumab (NAT), and dimethyl fumarate (DMF), and (b) Model 2: ALT relative to subcutaneous interferon beta-1a 44 µg (IFN beta-1a 44 µg). Both analyses were conducted from a U.S. third-party payer perspective. METHODS: Two static decision models were used to compare the cost-effectiveness of PEG and ALT over a 1-year and a 2-year time horizon, respectively. Model inputs were drug acquisition costs (wholesale acquisition cost from RED BOOK); drug administration and monitoring costs (package inserts and Centers for Medicare & Medicaid Services 2015 Physician Fee Schedule); relapse rates and relapse rate reduction (clinical trials); and cost of managing relapses (published literature). All costs were adjusted to 2015 U.S. dollars using the medical care component of the Consumer Price Index. Outcomes measured were total cost of therapy per patient, cost per relapse avoided, and incremental cost-effectiveness ratios (ICERs) calculated as cost per relapse avoided. Sensitivity analysis was conducted to test model robustness given the uncertainty of model inputs and study assumptions. RESULTS: Model 1 results showed that PEG dominated IM IFN and GA, compared with SC IFN; PEG had an ICER of $1,978,000 per relapse avoided. Compared with FIN, NAT, and DMF, PEG was less expensive and less effective. Model 2 showed that ALT had an ICER of $25,276 per relapse avoided relative to IFN beta-1a 44 µg. CONCLUSIONS: In patients with RRMS, PEG is a viable alternative when compared with the DMTs in our model. Deciding whether to choose PEG over other DMTs would depend on multiple factors. On the other hand, ALT had an ICER of $25,276 cost per relapse avoided relative to IFN beta-1a 44 µg. The study results will assist payers in evaluating different medication choices for effective therapy. DISCLOSURES: No outside funding supported this study. Kamal has received research funding from Novartis Pharmaceuticals and the College of Psychiatric and Neurologic Pharmacists and also serves as a consultant for the Lynx Group. Dashputre and Pawar report no conflicts of interest. Study concept and design were primarily contributed by Dashputre, along with Kamal and Pawar. Dashputre took the lead in data collection, along with Kamal, and data analysis was performed by Dashputre, Kamal, and Pawar. The manuscript was written and revised primarily by Dashputre, along with Kamal and Pawar.

Cost-effectiveness of oral agents in relapsing-remitting multiple sclerosis compared to interferon-based therapy in Saudi Arabia.

BACKGROUND: Promising clinical and humanistic outcomes are associated with the use of new oral agents in the treatment of relapsing-remitting multiple sclerosis (RRMS). This is the first cost-effectiveness study comparing these medications in Saudi Arabia. OBJECTIVES: We aimed to compare the cost-effectiveness of fingolimod, teriflunomide, dimethyl fumarate, and interferon (IFN)-b1a products (Avonex and Rebif) as first-line therapies in the treatment of patients with RRMS from a Saudi payer perspective. DESIGN: Cohort Simulation Model (Markov Model). SETTING: Tertiary care hospital. METHODS: A hypothetical cohort of 1000 RRMS Saudi patients was assumed to enter a Markov model model with a time horizon of 20 years and an annual cycle length. The model was developed based on an expanded disability status scale (EDSS) to evaluate the cost-effectiveness of the five disease-modifying drugs (DMDs) from a healthcare system perspective. Data on EDSS progression and relapse rates were obtained from the literature; cost data were obtained from King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. Results were expressed as incremental cost-effectiveness ratios (ICERs) and net monetary benefits (NMB) in Saudi Riyals and converted to equivalent $US. The base-case willingness-to-pay (WTP) threshold was assumed to be $100000 (SAR375000). One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to test the robustness of the model. MAIN OUTCOME MEASURES: ICERs and NMB. RESULTS: The base-case analysis results showed Rebif as the optimal therapy at a WTP threshold of $100000. Avonex had the lowest ICER value of $337282/QALY when compared to Rebif. One-way sensitivity analysis demonstrated that the results were sensitive to utility weights of health state three and four and the cost of Rebif. CONCLUSION: None of the DMDs were found to be cost-effective in the treatment of RRMS at a WTP threshold of $100000 in this analysis. The DMDs would only be cost-effective at a WTP above $300000. LIMITATIONS: The current analysis did not reflect the Saudi population preference in valuation of health states and did not consider the societal perspective in terms of cost.

Cost-Effectiveness of Treatments for Relapsing Remitting Multiple Sclerosis: A French Societal Perspective.

OBJECTIVES: The paper aimed to estimate the incremental cost-effectiveness ratio (ICER) at the public published price for delayed-release dimethyl fumarate versus relevant Multiple Sclerosis disease-modifying therapies available in France in June 2015. METHODS: The economic model was adapted to the French setting in accordance with the Haute Autorité de Santé guidelines using a model previously developed for NICE. A cohort of Relapsing Remitting Multiple Sclerosis patients was simulated over a 30-year time horizon. Twenty one health states were taken into account: Kurtzke Expanded Disability Status Scale (EDSS) 0-9 for Relapsing Remitting Multiple Sclerosis patients, EDSS 0-9 for Secondary Progressive Multiple Sclerosis patients, and death. Estimates of relative treatment efficacy were determined using a mixed-treatment comparison. Probabilities of events were derived from the dimethyl fumarate pivotal clinical trials and the London Ontario Dataset. Costs and utilities were extracted from the published literature from both the payer and societal perspectives. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model results. RESULTS: From both perspectives, dimethyl fumarate and interferon beta-1a (IFN beta-1a) 44 mcg were the two optimal treatments, as the other treatments (IFN beta-1a 30 mcg, IFN beta-1b 250 mcg, teriflunomide, glatiramer acetate, fingolimod) were dominated on the efficiency frontier. From the societal perspective, dimethyl fumarate versus IFN beta-1a 44 mcg incurred an incremental cost of €3,684 and an incremental quality-adjusted life year (QALY) of 0.281, corresponding to an ICER of €13,110/QALY. CONCLUSIONS: Despite no reference threshold for France, dimethyl fumarate can be considered as a cost-effective option as it is on the efficiency frontier.

Cost-effectiveness analysis of peginterferon beta-1a compared with interferon beta-1a and glatiramer acetate in the treatment of relapsing-remitting multiple sclerosis in the United States.

Objective Peginterferon beta-1a 125 mcg, administered subcutaneously (SC) every 2 weeks, a new disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS), was approved by the US Food and Drug Administration in 2014. This study assesses the cost-effectiveness of peginterferon beta-1a vs interferon beta-1a (44 mcg SC 3 times per week) and glatiramer acetate (20 mg SC once-daily) in the treatment of RRMS from the perspective of a US payer over 10 years. Methods A Markov cohort economic model was developed for this analysis. The model predicts disability progression, occurrence of relapses and other adverse events and translates them into quality-adjusted life years (QALYs) and costs. Natural history data were obtained from the placebo arm of the ADVANCE trial of peginterferon beta-1a, the London Ontario (Canada) database and a large population-based MS survey. Comparative efficacy of each DMT vs placebo was obtained from a network meta-analysis. Costs (in 2014 US dollars) were sourced from public databases and literature. Clinical and economic outcomes were discounted at 3% per year. Results Over 10 years, peginterferon beta-1a was dominant (i.e., more effective and less costly), with cost-savings of $22,070 and additional 0.06 QALYs when compared with interferon beta-1a 44 mcg and with cost-savings of $19,163 and 0.07 QALYs gained when compared with glatiramer acetate 20 mg. Results were most sensitive to variations in the treatment effect of each DMT, treatment acquisition costs of each DMT and the time horizon. Probabilistic sensitivity analyses indicated that peginterferon beta-1a remains dominant in >90% of 5,000 replications compared with either DMTs. Conclusion This analysis suggests that long-term treatment with peginterferon beta-1a improves clinical outcomes at reduced costs compared with interferon beta-1a 44 mcg and glatiramer acetate 20 mg and should be a valuable addition to managed care formularies for treating patients with RRMS.

The cost-effectiveness of delayed-release dimethyl fumarate for the treatment of relapsing-remitting multiple sclerosis in Canada.

BACKGROUND: Multiple sclerosis (MS) causes significant disability and diminished quality-of-life. Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) is a new oral treatment for relapsing-remitting MS (RRMS) approved in the US, Australia, Canada, and Europe. OBJECTIVES: A cost-effectiveness model was developed to compare the health economic impact of DMF against other disease-modifying therapies (DMTs) as first-line RRMS treatment from a Canadian Ministry of Health perspective. METHODS: A Markov cohort model was developed to simulate patients' progression through health states based on the Kurtzke Expanded Disability Status Scale (EDSS) over a life-time horizon. Patients entered the model based on a distribution of baseline EDSS scores, from which they could progress to higher or regress to lower EDSS state, or remain in the same state. Relapses could occur at any EDSS score. Results from a mixed-treatment comparison were used to inform model inputs for disease progression and relapse rates per treatment. Costs included direct medical costs stratified by EDSS score. Utilities were accrued based on time spent in each EDSS state. RESULTS: Compared with glatiramer acetate, DMF yielded 0.528 incremental quality-adjusted life-years (QALYs) at an incremental cost of $23 338 Canadian dollars (CAD), resulting in an incremental cost-effectiveness ratio (ICER) of CAD $44 118/QALY. The ICER for DMF compared with Rebif 44 mcg was CAD $10 672. Results were consistent across a wide range of one-way and probabilistic sensitivity analyses. CONCLUSIONS: Based on traditional cost-effectiveness thresholds in Canada (CAD $50 000-60 000), DMF can be considered a cost-effective option compared to other first-line DMTs.