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.     

Cost-effectiveness of glatiramer acetate and interferon beta-1a for relapsing-remitting multiple sclerosis,based on the CombiRx study

Background:

To assess the cost-effectiveness of the Disease Modifying Treatments (DMT), Glatiramer Acetate (GA) and Interferon beta-1a (IFN) in monotherapy alone and in combination for the prevention of relapses among Spanish patients aged between 18–60 years old with established Relapsing–Remitting Multiple Sclerosis (RRMS).

Methods:

A Markov model was developed to represent the transition of a cohort of patients over a 10 year period using the perspective of the Spanish National Health Service (NHS). The model considered five different health states with 1-year cycles including without relapse, patients with suspect, non-protocol defined and protocol defined exacerbations, as well as a category information lost. Efficacy data was obtained from the 3-year CombiRx Study. Costs were reported in 2013 Euros and a 3% discount rate was applied for health and benefits. Deterministic results were presented as the annual treatment cost for the number of relapses. A probabilistic sensitivity analysis was performed to test the robustness of the model.

Results:

Deterministic results showed that the expected annual cost per patient was lower when treated with GA (€13,843) compared with IFN (€15,589) and the combined treatment with IFN?+?GA (€21,539). The annual number of relapses were lower in the GA cohort with 3.81 vs 4.18 in the IFN cohort and 4.08 in the cohort treated with IFN?+?GA. Results from probabilistic sensitivity analysis showed that GA has a higher probability of being cost-effective than treatment with IFN or IFN?+?GA for threshold values from €28,000 onwards, independent of the maximum that the Spanish NHS is willing to pay for avoiding relapses.

Conclusion:

GA was shown to be a cost-effective treatment option for the prevention of relapses in Spanish patients diagnosed with RRMS. When GA in monotherapy is compared with INF in monotherapy and IFN?+?GA combined, it may be concluded that the first is the dominant strategy.     

The effect of age and sex on cost of inpatient facility encounters among patients with multiple sclerosis

Abstract

Objective:

To explore the effect of age and sex on cost of all-cause and multiple sclerosis (MS)-related inpatient facility encounters.     

Fingolimod reduces direct medical costs compared to natalizumab in patients with relapsing–remitting multiple sclerosis in The Netherlands

Abstract

Objective:

To assess the costs of oral treatment with Gilenya® (fingolimod) compared to intravenous infusion of Tysabri® (natalizumab) in patients with relapsing–remitting multiple sclerosis (RRMS) in The Netherlands.

Methods:

A cost-minimization analysis was used to compare both treatments. The following cost categories were distinguished: drug acquisition costs, administration costs, and monitoring costs. Costs were discounted at 4%, and incremental model results were presented over a 1, 2, 5, and 10 year time horizon. The robustness of the results was determined by means of a number of deterministic univariate sensitivity analyses. Additionally, a break-even analysis was carried out to determine at which natalizumab infusion costs a cost-neutral outcome would be obtained.

Results:

Comparing fingolimod to natalizumab, the model predicted discounted incremental costs of ?€2966 (95% CI: ?€4209; ?€1801), ?€6240 (95% CI: ?€8800; ?€3879), ?€15,328 (95% CI: ?€21,539; ?€9692), and ?€28,287 (95% CI: ?€39,661; ?€17,955) over a 1, 2, 5, and 10-year time horizon, respectively. These predictions were most sensitive to changes in the costs of natalizumab infusion. Changing these costs of €255 within a range from €165–364 per infusion resulted in cost savings varying from €4031 to €8923 after 2 years. The additional break-even analysis showed that infusion costs—including aseptic preparation of the natalizumab solution—needed to be as low as the respective costs of €94 and €80 to obtain a cost neutral result after 2 and 10 years.

Limitations:

Neither treatment discontinuation and subsequent re-initiation nor patient compliance were taken into account. As a consequence of the applied cost-minimization technique, only direct medical costs were included.

Conclusion:

The present analysis showed that treatment with fingolimod resulted in considerable cost savings compared to natalizumab: starting at €2966 in the first year, increasing to a total of €28,287 after 10 years per RRMS patient in the Netherlands.     

Cost-effectiveness analysis of disease modifiying drugs (interferons and glatiramer acetate) as first line treatments in remitting-relapsing multiple sclerosis patients

Abstract

Objective:

The aim of this study was to assess cost-effectiveness of the different Disease Modifying Drugs (DMD) used as first-line treatments (interferons IM IFNβ-1a, SC IFNβ-1a, SC IFNβ-1b, and glatiramer acetate, GA) in Remitting-Relapsing Multiple Sclerosis (RRMS) in Spain.

Methods:

A Markov model was developed to simulate the progression of a cohort of patients with RRMS, during a period of 10 years. Seven health states, defined by the Expanded Disability Status Scale (EDSS), were considered in the model. Patients with an EDSS score less than 6.0 were assumed to be treated with one of the DMD. In addition, all patients were assumed to receive symptomatic treatment. The monthly transition probabilities of the model were obtained from the literature. The analysis was performed from the societal perspective, in which both direct and indirect (losses in productivity) healthcare costs (€, 2010) were included. A discount rate of 3% was applied to both costs and efficacy results.

Results:

GA was the less costly strategy (€322,510), followed by IM IFNβ-1a (€329,595), SC IFNβ-1b (€ 333,925), and SC IFNβ-1a (€348,208). IM IFNβ-1a has shown the best efficacy results, with 4.176 quality-adjusted life years (QALY), followed by SC IFNβ-1a (4.158 QALY), SC IFNβ-1b (4.157 QALY), and GA (4.117 QALY). Incremental costs per QALY gained with IM IFNβ-1a were €?1,005,194/QALY, €?223,397/QALY, and €117,914/QALY in comparison to SC IFNβ-1a, SC IFNβ-1b, and GA, respectively.

Conclusions:

First-line treatment with GA is the less costly strategy for the treatment of patients with RRMS. Treatment with IM IFNβ-1a is a dominant strategy (lower cost and higher QALY) compared with SC IFNβ-1a and SC IFNβ-1b. However, IM IFNβ-1a is not a cost-effective strategy vs GA, because incremental cost per QALY gained with IM IFNβ-1a exceeds the €30,000 per QALY threshold commonly used in Spain.

Limitations:

The highly-restrictive inclusion criteria of clinical trials limits generalization of the results on efficacy to all patients with multiple sclerosis. Availability of data for head-to-head comparisons is associated with the use of information from clinical trials.     

A discrete choice experiment to determine UK patient preference for attributes of disease modifying treatments in Multiple Sclerosis

Aims: The recent licensing of Disease Modifying Treatments (DMTs) for Multiple Sclerosis (MS) has increased available treatment options. The aim of this study was to explore MS patients’ preference for the different attributes of DMTs in the UK.

Materials and methods: Attributes (treatment characteristics) for inclusion in the discrete choice experiment (DCE) were determined through published literature and interviews with 12 people with MS. Seven attributes were selected. Participants were presented with three hypothetical treatment options sampled from included attributes and asked for their most/least preferred options. The influence of patient characteristics and demographics on patient preference was also investigated.

Results: The DCE was completed by 350 people with MS (81% female, mean age?=?39). Results showed that method of taking medication was the strongest determinant of preference (27%; relative importance out of 100%), followed by relapse free rate (21%) and symptom progression (14%). Risk of fatigue (8%) and type of monitoring (6%) were the weakest determinants of preference. Once-daily oral treatment was preferred over all other methods of administration. Participant characteristics did not influence data on strength of preference.

Limitations: This study assumed adequate participant understanding of the discrete choice experiment task, and recruitment targeted those with access to the internet.

Conclusions: These results, derived from people with MS in the UK, should be used to inform individual discussions with patients about DMT choices.     

Cost-effectiveness of asenapine in the treatment of bipolar I disorder patients with mixed episodes

Objective:

Around one-third of patients with bipolar I disorder (BD-I) experience mixed episodes, characterized by both mania and depression, which tend to be more difficult and costly to treat. Atypical antipsychotics are recommended for the treatment of mixed episodes, although evidence of their efficacy, tolerability, and cost in these patients is limited. This study evaluates, from a UK National Health Service perspective, the cost-effectiveness of asenapine vs olanzapine in BD-I patients with mixed episodes.

Methods:

Cost-effectiveness was assessed using a Markov model. Efficacy was informed by a post-hoc analysis of two short-term clinical trials, with response measured as a composite Young Mania Rating Score and Montgomery-Åsberg Depression Rating Scale end-point. Probabilities of discontinuation and relapse to manic, mixed, and depressive episodes were sourced from published meta-analyses. Direct costs (2012–2013 values) included drug acquisition, monitoring, and resource use related to bipolar disorder as well as selected adverse events. Benefits were measured as quality-adjusted life years (QALYs).

Results:

For treating mixed episodes, asenapine generated 0.0187 more QALYs for an additional cost of £24 compared to olanzapine over a 5-year period, corresponding to a £1302 incremental cost-effectiveness ratio. The higher acquisition cost of asenapine was roughly offset by the healthcare savings conferred through its greater efficacy in treating these patients. The model shows that benefits were driven by earlier response to asenapine during acute treatment and were maintained during longer-term follow-up. Results were sensitive to changes in key parameters including short and longer-term efficacy, unit cost, and utilities, but conclusions remained relatively robust.

Conclusions:

Results suggest that asenapine is a cost-effective alternative to olanzapine in mixed episode BD-I patients, and may have specific advantages in this population, potentially leading to healthcare sector savings and improved outcomes. Limitations of the analysis stem from gaps in clinical and economic evidence for these patients and should be addressed by future clinical trials.     

Cost-effectiveness of natalizumab versus fingolimod for the treatment of relapsing multiple sclerosis

Abstract

Background:

With the addition of new agents for the treatment of multiple sclerosis (MS) (e.g., fingolimod), there is a need to evaluate the relative value of newer therapies in terms of cost and effectiveness, given healthcare resource constraints in the United States.

Objective:

To assess the cost-effectiveness of natalizumab vs fingolimod in patients with relapsing MS.

Methods:

A decision analytic model was developed to estimate the incremental cost per relapse avoided of natalizumab and fingolimod from a US managed care payer perspective. Two-year costs of treating patients with MS included drug acquisition costs, administration and monitoring costs, and costs of treating MS relapses. Effectiveness was measured in terms of MS relapses avoided (data from AFFIRM and FREEDOMS trials). One-way and probabilistic sensitivity analyses were conducted to assess uncertainty.

Results:

Mean 2-year estimated treatment costs were $86,461 (natalizumab) and $98,748 (fingolimod). Patients receiving natalizumab had a mean of 0.74 relapses avoided per 2 years vs 0.59 for fingolimod. Natalizumab dominated fingolimod in the incremental cost-effectiveness analysis, as it was less costly and more effective in reducing relapses. One-way sensitivity analysis showed the results of the model were robust to changes in drug acquisition costs, administration costs, and costs of treating MS relapses. Probabilistic sensitivity analysis showed natalizumab was cost-effective 95.1% of the time, at a willingness-to-pay (WTP) threshold of $0 per relapse avoided, increasing to 96.3% of the time at a WTP threshold of $50,000 per relapse avoided.

Limitations:

Absence of data from direct head-to-head studies comparing natalizumab and fingolimod, use of relapse rate reduction rather than sustained disability progression as primary model outcome, assumption of 100% adherence to MS treatment, and not capturing adverse event costs in the model.

Conclusions:

Natalizumab dominates fingolimod in terms of incremental cost per relapse avoided, as it is less costly and more effective.     

Cost-effectiveness of natalizumab vs fingolimod for the treatment of relapsing-remitting multiple sclerosis: analyses in Sweden

Abstract

Objective:

To assess the cost-effectiveness of natalizumab vs fingolimod over 2 years in relapsing-remitting multiple sclerosis (RRMS) patients and patients with rapidly evolving severe disease in Sweden.

Methods:

A decision analytic model was developed to estimate the incremental cost per relapse avoided of natalizumab and fingolimod from the perspective of the Swedish healthcare system. Modeled 2-year costs in Swedish kronor of treating RRMS patients included drug acquisition costs, administration and monitoring costs, and costs of treating MS relapses. Effectiveness was measured in terms of MS relapses avoided using data from the AFFIRM and FREEDOMS trials for all patients with RRMS and from post-hoc sub-group analyses for patients with rapidly evolving severe disease. Probabilistic sensitivity analyses were conducted to assess uncertainty.

Results:

The analysis showed that, in all patients with MS, treatment with fingolimod costs less (440,463 Kr vs 444,324 Kr), but treatment with natalizumab results in more relapses avoided (0.74 vs 0.59), resulting in an incremental cost-effectiveness ratio (ICER) of 25,448 Kr per relapse avoided. In patients with rapidly evolving severe disease, natalizumab dominated fingolimod. Results of the sensitivity analysis demonstrate the robustness of the model results. At a willingness-to-pay (WTP) threshold of 500,000 Kr per relapse avoided, natalizumab is cost-effective in >80% of simulations in both patient populations.

Limitations:

Limitations include absence of data from direct head-to-head studies comparing natalizumab and fingolimod, use of relapse rate reduction rather than sustained disability progression as the primary model outcome, assumption of 100% adherence to MS treatment, and exclusion of adverse event costs in the model.

Conclusions:

Natalizumab remains a cost-effective treatment option for patients with MS in Sweden. In the RRMS patient population, the incremental cost per relapse avoided is well below a 500,000 Kr WTP threshold per relapse avoided. In the rapidly evolving severe disease patient population, natalizumab dominates fingolimod.     

Literature-related discovery (LRD): Potential treatments for Multiple Sclerosis

Literature-related discovery (LRD) is the linking of two or more literature concepts that have heretofore not been linked (i.e., disjoint), in order to produce novel, interesting, plausible, and intelligible knowledge (i.e., potential discovery). The open discovery systems (ODS) component of LRD starts with a problem to be solved, and generates solutions to that problem through potential discovery. We have been using ODS LRD to identify potential treatments or preventative actions for challenging medical problems, among myriad other applications. The previous three papers in this Special Issue describe the application of ODS LRD to Raynaud's Phenomenon (RP), cataracts, and Parkinson's Disease (PD).Multiple Sclerosis (MS) is a progressive neurodegenerative disorder (typically preceded by periods of remission and relapse), affecting mainly people in their early-mid life. MS is characterized by changes in sensation (hypoesthesia), muscle weakness, abnormal muscle spasms, or difficulty to move; difficulties with coordination and balance (ataxia); problems in speech (Dysarthria) or swallowing (Dysphagia), visual problems (Nystagmus, optic neuritis, or diplopia), fatigue and acute or chronic pain syndromes, bladder and bowel difficulties, cognitive impairment, or emotional symptomatology (mainly depression).We selected the subject of MS because of its global prevalence, and its apparent intractability to all treatments except for palliative remediation mainly through drugs or surgery. Our first goal was to identify non-drug non-surgical treatments that would 1) prevent the occurrence, or 2) reduce the progression rate, or 3) stop the progression, or 4) maybe even reverse the progression, of MS. Our second goal was to demonstrate that we could again solve an ODS problem (using LRD) with no prior knowledge of any results or prior work (unlike the case of the RP problem). As in the ‘cataract’ and PD examples, we used the MeSH taxonomy of MEDLINE to restrict potential discoveries to selected semantic classes, and to identify potential discoveries efficiently. Our third goal was to generate large amounts of potential discovery in more than an order of magnitude less time than required for the RP study. The discovery generation methodology has been developed to the point where ODS LRD problems can be solved with no results or knowledge of any prior work.     

Treatment experience,burden, and unmet needs (TRIBUNE) in Multiple Sclerosis study: the costs and utilities of MS patients in The Netherlands

Abstract

Background:

Multiple sclerosis (MS) is an important, highly disabling neurological disease, common among young adults in The Netherlands. Nevertheless, only a few studies to date have measured the burden imposed by MS on society in The Netherlands.

Objectives:

To estimate the cost and quality-of-life associated with MS in The Netherlands, while focusing on the burden of relapses and increasing disease severity.

Methods:

MS patients in The Netherlands (n?=?263) completed a web-based questionnaire which captured information on demographics, disease characteristics and severity (Expanded Disability Status Scale [EDSS]), co-morbidities, relapses, resource consumption, utilities, fatigue and activities of daily living (ADL).

Results:

Most patients included in the study were receiving treatment for MS (76% of the sample). The mean cost per patient per year increased with worsening disability and was estimated at €30,938, €51,056, and €100,469 for patients with mild (EDSS 0–3), moderate (EDSS 4–6.5), and severe (EDSS 7–9) disability, respectively. The excess cost of relapses was estimated at €8195 among relapsing-remitting patients with EDSS score ≤5. The quality-of-life of patients decreased with disease progression and existence of relapses.

Conclusions:

The cost of MS in The Netherlands was higher compared to the results of previous studies. The TRIBUNE study provides an important update on the economic burden of MS in The Netherlands in an era of more widespread use of disease-modifying therapies. It explores the cost of MS linked to relapses and disease severity and examines the impact of MS on additional health outcomes beyond utilities such as ADL and fatigue.

Conclusions:

Study limitations:     

Real-world cost of treatment for multiple sclerosis patients initiating and receiving infused disease-modifying therapies per recommended label in the United States

Abstract

Aims: The study evaluated the real-world cost of treatment in multiple sclerosis (MS) patients initiating infused disease-modifying-therapies (DMT) in the United States.

Materials and Methods: This retrospective cohort study using administrative claims data included adult patients with MS initiating index infusion DMT (ocrelizumab (OCR), natalizumab (NTZ) or alemtuzumab (ATZ)) from April 2017–September 2018 with 6-months pre/12-months post-index continuous enrollment. The primary cohort included patients who had prescribed annual dosing visits indicated by the approved product label (PL): 3 OCR, 5 ATZ, and 12–13 NTZ infusion visits within the first year of initiation. Annual treatment cost was the sum of all costs on index DMT infusion visit dates. Costs were summarized for a primary and secondary cohort of patients receiving additional doses than prescribed in PL (>3 OCR, >5 ATZ, and >13 NTZ infusion visits); and an overall cohort of patients who met minimum required annual dose (≥3 OCR, ≥5 ATZ, and ≥12 NTZ), further stratified by insurance type.

Results: For patients in the primary cohort (123 OCR, 18 ATZ, and 48 NTZ), mean (standard-deviation) annual cost of treatment with OCR, ATZ, and NTZ cohorts was $72,066 ($34,480), $121,053 ($51,097) and $93,777 ($38,815), respectively. Among patients initiating OCR and NTZ, 15 and 6% respectively, had additional infusion visits leading to greater costs. Mean annual costs of index infusion DMT treatment in the overall cohort (162 patients treated with OCR, 18 with ATZ, 56 with NTZ) were $80,582, $121,053, and $93,807, respectively. The mean costs for commercial enrollees were higher than those for MAPD enrollees.

Limitations: Small sample size, limited population generalizability, and cost-reduction for ATZ beyond the second year need to be accounted for.

Conclusions: Real-world infusion DMT treatment costs for commercially insured patients were higher than perceived expenditures based on wholesale acquisition cost and administration costs via a physician-fee schedule. Consideration of real-world costs in cost-effectiveness and treatment/coverage decisions is needed.     

Cost-effectiveness of delayed-release dimethyl fumarate for the treatment of relapsing forms of multiple sclerosis in the United States

Objective:

To assess the cost-effectiveness of delayed-release dimethyl fumarate (DMF, also known as gastro-resistant DMF), an effective therapy for relapsing forms of multiple sclerosis (MS), compared with glatiramer acetate and fingolimod, commonly used treatments in the US.

Methods:

A Markov model was developed comparing delayed-release DMF to glatiramer acetate and fingolimod using a US payer perspective and 20-year time horizon. A cohort of patients, mean age 38 years, with relapsing-remitting MS and Kurtzke Expanded Disability Status Scale (EDSS) scores between 0–6 entered the model. Efficacy and safety were estimated by mixed-treatment comparison of data from the DEFINE and CONFIRM trials and clinical trials of other disease-modifying therapies. Data from published studies were used to derive resource use, cost, and utility inputs. Key outcomes included costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Alternative scenarios tested in a sensitivity analysis included drug efficacy, EDSS-related or relapse-related costs, alternative perspectives, drug acquisition costs, and utility.

Results:

Base-case results with a 20-year time horizon indicated that delayed-release DMF increased QALYs +0.450 or +0.359 compared with glatiramer acetate or fingolimod, respectively. Reductions in 20-year costs with delayed-release DMF were ?$70,644 compared with once-daily glatiramer acetate and ?$32,958 compared with fingolimod. In an analysis comparing delayed-release DMF to three-times-weekly glatiramer acetate and assuming similar efficacy and safety to the once-daily formulation, 20-year costs with delayed-release DMF were increased by $15,806 and cost per QALY gained was $35,142. The differences in costs were most sensitive to acquisition cost and inclusion of informal care costs and productivity losses. The differences in QALYs were most sensitive to the impact of delayed-release DMF on disease progression and the EDSS utility weights.

Conclusion:

Delayed-release DMF is likely to increase QALYs for patients with relapsing forms of MS and be cost-effective compared with fingolimod and glatiramer acetate.     

Cost-effectiveness of risk stratification for preventing type 2 diabetes using a multi-marker diabetes risk score

Abstract

Background:

Personalized medicine requires diagnostic tests that stratify patients into distinct groups that may differentially benefit from targeted treatment approaches. This study compared the costs and benefits of two approaches for identifying those at high risk of developing type 2 diabetes for entry into a diabetes prevention program. The first approach identified high risk patients using impaired fasting glucose (IFG). The second approach used the PreDx Diabetes Risk Score (DRS) to further stratify IFG patients into high-risk and moderate-risk groups.

Methods:

A Markov model was developed to simulate the incidence and disease progression of diabetes and consequent costs and quality-adjusted life expectancy (QALY), comparing alternative approaches for identifying high-risk patients. We modeled direct medical costs, including the costs of the stratification testing, over a 10-year time horizon from a US payer perspective.

Results:

Stratification of IFG patients by the DRS method leads to improved identification and prevention among those at highest risk. At 5 years, the number needed to treat (NNT) in the IFG-only approach was 39 patients to prevent one case of diabetes compared to an NNT of 15 in the IFG?+?DRS approach. When compared to IFG alone, the IFG?+?DRS approach results in an incremental cost-effectiveness ratio (ICER) of $17,100/QALY gained at 5 years and would become cost saving in 10 years. In contrast and as compared to no stratification, the IFG-only approach would produce an ICER of $235,500/QALY gained at 5 years and $94,600/QALY gained at 10 years. The study findings are limited by the generalizability of the DRS validation study and uncertainty regarding the long-term effectiveness of diabetes prevention.

Conclusions:

The analysis indicates that the cost-effectiveness of diabetes prevention can be improved by better identification of patients at highest risk for diabetes using the DRS.     

Impact of increasing adherence to disease-modifying therapies on healthcare resource utilization and direct medical and indirect work loss costs for patients with multiple sclerosis

Abstract

Objectives:

To estimate the effect of adherence to disease-modifying therapies (DMTs) among patients with multiple sclerosis (MS) on healthcare resource utilization (HRU) and costs, and model the impact of a 10 percentage point increase in adherence on these outcomes.     

Cost-effectiveness of fingolimod versus interferon beta-1a for relapsing remitting multiple sclerosis in the United States

Abstract

Objective:

Fingolimod has been shown to be more efficacious than interferon (IFN) beta-1a, but at a higher drug acquisition cost. The aim of this study was to assess the cost-effectiveness of fingolimod compared to IFN beta-1a in patients diagnosed with relapsing-remitting multiple sclerosis (RRMS) in the US.

Methods:

A Markov model comparing fingolimod to intramuscular IFN beta-1a using a US societal perspective and a 10-year time horizon was developed. A cohort of 37-year-old patients with RRMS and a Kurtzke Expanded Disability Status Scale score of 0–2.5 were assumed. Data sources included the Trial Assessing Injectable Interferon vs FTY720 Oral in Relapsing–Remitting Multiple Sclerosis (TRANSFORMS) and other published studies of MS. Outcomes included costs in 2011 US dollars, quality-adjusted life years (QALYs), number of relapses avoided, and incremental cost-effectiveness ratios (ICERs).

Results:

Compared to IFN beta-1a, fingolimod was associated with fewer relapses (0.41 vs 0.73 per patient per year) and more QALYs gained (6.7663 vs 5.9503), but at a higher cost ($565,598 vs $505,234). This resulted in an ICER of $73,975 per QALY. Results were most sensitive to changes in drug costs and the disutility of receiving IFN beta-1a. Monte Carlo simulation demonstrated fingolimod was cost-effective in 35% and 70% of 10,000 iterations, assuming willingness-to-pay thresholds of $50,000 and $100,000 per QALY, respectively.

Limitations:

Event rates were primarily derived from a single randomized clinical trial with 1-year duration of follow-up and extrapolated to a 10-year time horizon. Comparison was made to only one disease-modifying drug—intramuscular IFN beta-1a.

Conclusion:

Fingolimod use is not likely to be cost-effective compared to IFN beta-1a unless fingolimod cost falls below $3476 per month or a higher than normal willingness-to-pay threshold is accepted by decision-makers.     

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.