Cost Effectiveness of Fingolimod, Teriflunomide, Dimethyl Fumarate and Intramuscular Interferon-β1a in Relapsing-Remitting Multiple Sclerosis

Zhang, Xinke; Hay, Joel W.; Niu, Xiaoli

doi:10.1007/s40263-014-0207-x

Cited by 27 publications

(33 citation statements)

References 49 publications

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“…This analysis, adopting the Italian societal perspective, reinforces the findings of a previous analysis conducted on dimethyl fumarate and adopting the Italian NHS perspective [49]. Furthermore, the results from the Italian analysis are in line with those reported for USA [50] and other countries of Europe [51][52][53][54][55].…”

Section: Discussionsupporting

confidence: 88%

Cost-Effectiveness Analysis of Dimethyl Fumarate in the Treatment of Relapsing Remitting Multiple Sclerosis: An Italian Societal Perspective

Mantovani

Furneri²,

Bitonti³

et al. 2019

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BACKGROUND: Delayed-release dimethyl fumarate (also known as gastro-resistant dimethyl fumarate, hereafter dimethyl fumarate) is an oral disease-modifying therapy used for the treatment of Relapsing-Remitting Multiple Sclerosis (RRMS), an autoimmune chronic inflammatory condition of the central nervous system.OBJECTIVE: The objective of this economic analysis was to compare cost-effectiveness of dimethyl fumarate with the alternatives used as first-line treatment of RRMS in Italy.METHODS: The analysis was conducted from the Italian societal perspective. Health outcomes and costs were evaluated over a 50-year time horizon (equivalent to a lifetime horizon). Both health outcomes and costs were discounted at 3.5%. The cost-effectiveness analysis was conducted by adapting a Markov model, already used in previous similar economic analyses conducted in RRMS, to the Italian context. The Markov model estimated the clinical and economic consequences of treating RRMS patients with the following therapeutic options: dimethyl fumarate; interferon (IFN) beta-1a subcutaneous (SC) at two different doses, 22 mcg and 44 mcg; IFN beta-1b SC; glatiramer acetate (GA) SC 20 mg; oral teriflunomide. Clinical efficacy data were retrieved from an elaboration of an already published mixed treatment comparison (MTC). Both direct and indirect costs (disability, treatment acquisition, administration, monitoring, relapses, adverse events) were included in the analysis. One-way and probabilistic sensitivity analyses were carried out and cost-effectiveness acceptability curves generated.RESULTS: In the base-case analysis, dimethyl fumarate was more efficacious than alternatives, in terms of both survival (19.634 vs. 19.440-19.600 life years for alternatives), and quality-of-life-adjusted survival (6.526 vs. 5.143- 6.189 QALYs for alternatives). The total lifetime cost per patient treated with dimethyl fumarate (€ 954,286) was lower than that of the other DMTs included in the analysis. Therefore, dimethyl fumarate was dominant compared with all analyzed alternatives. Dimethyl fumarate was also the therapeutic option with the highest benefit on disease burden. In fact, costs of disability management were lower than those of all the other first-line drugs included in the analysis. The results of one-way deterministic sensitivity analysis and probabilistic sensitivity analysis confirmed the reliability of base-case results.CONCLUSIONS: The results of the cost-effectiveness analysis confirm that dimethyl fumarate is an optimal first-line treatment for RRMS in Italy, compared with the other first-line alternatives included in the economic analysis, when evaluated from the societal perspective.

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Section: Discussionsupporting

confidence: 88%

Cost-Effectiveness Analysis of Dimethyl Fumarate in the Treatment of Relapsing Remitting Multiple Sclerosis: An Italian Societal Perspective

Mantovani

Furneri²,

Bitonti³

et al. 2019

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“…Dimethyl fumarate is used clinically to treat chronic inflammatory disorders, namely psoriasis (where DMF is combined in a fixed combination with other fumaric acid esters) and multiple sclerosis (where DMF is the only active ingredient in the marketed formulation), both of which are characterised by a TNFα‐governed microenvironment within the inflamed tissues . If tolerated well and monitored correctly, fumaric acid ester therapy is safe and can be of great value for the patients at a reasonable cost–benefit–risk ratio . In many cases, however, dose‐dependent unwanted side effects such as gastrointestinal ailments or lymphocytopenia lead to premature therapy discontinuation .…”

Section: Discussionmentioning

confidence: 99%

Mutually enhancing anti‐inflammatory activities of dimethyl fumarate and NF‐κB inhibitors – implications for dose‐sparing combination therapies

Hund

Lockmann

Schön

2016

Experimental Dermatology

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Fumaric acid esters, dimethyl fumarate (DMF) in particular, have been established for the therapy of psoriasis and, more recently, multiple sclerosis. In the light of therapy-limiting dose-dependent side effects, such as gastrointestinal irritation, reducing the effective doses of FAE is a worthwhile goal. In search of strategies to maintain the anti-inflammatory activity of DMF at reduced concentrations, we found that NF-κB inhibition augmented key anti-inflammatory effects of DMF in two complementary experimental settings in vitro. At non-toxic concentrations, both proteasome inhibition with bortezomib as well as blocking NF-κB activation through KINK-1, a small molecule inhibitor of IKKβ-profoundly enhanced DMF-dependent inhibition of nuclear NF-κB translocation in TNFα-stimulated human endothelial cells. This resulted in significant and selective co-operative down-regulation of endothelial adhesion molecules crucial for leucocyte extravasation, namely E-selectin (CD62E), VCAM-1 (CD106) and ICAM-1 (CD54), on both mRNA and protein levels. Functionally, these molecular changes led to synergistically decreased rolling and firm adhesion of human lymphocytes on TNF-activated endothelial cells, as demonstrated in a dynamic flow chamber system. If our in vitro findings can be translated into clinical settings, it is conceivable that anti-inflammatory effects of DMF can be achieved with lower doses than currently used, thus potentially reducing unwanted side effects.

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“…Comunque, a nostra conoscenza, in letteratura è presente un sola valutazione economica che abbia utilizzato un modello farmacoeconomico in SM con un trattamento successivo al primo. La valutazione è stata condotta nella prospettiva della società USA e non include peginterferone beta-1a tra i farmaci in studio [81]. Un altro limite è rappresentato dal valore utilizzato per il costo della ricaduta nella prospettiva del SSN italiano.…”

Section: Analisi DI Costo-efficacia Dell'utilizzo Di Peginterferone Bunclassified

[Cost-effectiveness analysis of peginterferon beta-1a in Italian relapsing remitting multiple sclerosis management]

Iannazzo¹,

Santoni²,

Saleri³

et al. 2016

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cronicità e la progressione della malattia con ricadute e disabilità crescente incidono sulla qualità di vita del paziente e sui costi per la società. L'esordio della malattia nella fase giovaneadulta coincide con il pieno della vita affetIntroduzIone L'organizzazione mondiale della sanità (OMS) ha definito la sclerosi multipla (SM) una delle malattie sociali maggiormente costose. L'esordio nella fase giovane-adulta, la AbstrActBACKGROUND: Peginterferon beta-1a is indicated in adult patients for the treatment of relapsing remitting multiple sclerosis (RRMS). The efficacy and safety of peginterferon beta-1a was demonstrated in the placebo-controlled ADVANCE trial. OBJECTIVE: The objective of this study was to assess the cost-effectiveness of peginterferon beta-1a as compared with injectable first-line treatments for RRMS in Italy. METHODS: The cost-effectiveness analysis was developed through a Markov model with lifetime simulation in the perspective of the Italian National Healthcare Service (NHS). It was added an alternative scenario to take into account the Italian societal perspective. Outcomes were measured in terms of life years (LYs), quality adjusted life years (QALYs), lifetime costs and incremental cost-effectiveness ratio (ICER). The natural progression of the disease was informed by the published literature and previously published modelling exercises. The efficacy of treatments was simulated as reduction of disability progression (EDSS) and relapse rate. Efficacy data were derived from a published network meta-analysis. Unit costs were based on current prices and tariffs, and the published literature. A 3.5% discount rate was applied to costs and outcomes. One-way and probabilistic sensitivity analyses were developed and cost-effectiveness acceptability curves generated. RESULTS: Peginterferon beta-1a was more effective than the comparators in terms of survival (19.94 vs.19.68-19.81 discounted LYs, respectively), and QALYs (9.07 vs. 8.06 and 8.55 discounted QALY, respectively). In the perspective of the Italian NHS, the ICER was € 11,111/QALY vs. interferon beta-1a 30 µg, € 12,604/QALY vs. interferon beta-1a 22 µg, € 10,580/QALY and € 16,702/QALY vs. interferon beta-1b 250 µg and € 22,023/QALY vs. glatiramer acetate 20 mg. Peginterferon beta-1a dominated interferon beta-1a 44 µg. In the societal perspective, peginterferon beta-1a was dominant due to being more effective and with a lower social cost compared to first-line injectable treatments (interferon beta -1a, interferon beta-1b, glatiramer acetate) for RRMS. The outcomes of the sensitivity analyses confirmed the trend of the base case results. CONCLUSIONS: Peginterferon beta-1a shows a favourable pharmaco-economic profile for the treatment of RRMS. Even if an official threshold for the cost-effectiveness does not exist in Italy, the ICER values obtained were far below the commonly accepted thresholds (30,000-50,000 €/per QALY gained). Keywords Cost-effectiveness; Peginterferon beta-1a; Multiple SclerosisAnalisi di costo-efficacia dell'utilizzo ...

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Cost Effectiveness of Fingolimod, Teriflunomide, Dimethyl Fumarate and Intramuscular Interferon-β1a in Relapsing-Remitting Multiple Sclerosis

Abstract: The three oral therapies were favored in the cost-effectiveness analysis. Of the four DMDs, dimethyl fumarate was a dominant therapy to manage RRMS. Apart from dimethyl fumarate, teriflunomide was the most cost-effective therapy compared with IM IFN-β(1a), with an ICER of US$7,115.

Cited by 27 publications

References 49 publications

Cost-Effectiveness Analysis of Dimethyl Fumarate in the Treatment of Relapsing Remitting Multiple Sclerosis: An Italian Societal Perspective

Cost-Effectiveness Analysis of Dimethyl Fumarate in the Treatment of Relapsing Remitting Multiple Sclerosis: An Italian Societal Perspective

Mutually enhancing anti‐inflammatory activities of dimethyl fumarate and NF‐κB inhibitors – implications for dose‐sparing combination therapies

[Cost-effectiveness analysis of peginterferon beta-1a in Italian relapsing remitting multiple sclerosis management]

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