Table 2 Characteristics of studies included in the review
First author’s name (Year) | Costing year | Setting | Population | Compared interventions | Type of economic evaluation | Perspective | Time horizon | WTP Threshold | Discount rate | Sensitivity analyses | Quality index decision based on % score | Sponsor |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
Smets et al. (2023) [53] | 2022 | Netherlands | 1000 pwMS | Ocrelizumab/ ofatumumab compared with eight other drug classes | Health outcomes (i.e., lifetime relapses, time to Expanded Disability Status Scale [EDSS] 6), lifetime quality-adjusted life years [QALYs]) and cost-effectiveness (i.e., net health benefit [NHB]) (the ErasmusMC/iMTA MS) | Health-economic and societal perspective | Lifetime | Monetary value of a QALY (€50,000 for MS in The Netherlands) / willingness-to-pay’ of €50,000 per QALY | Costs: 4%, effects 1.5% | Probabilistic analysis | High | Dutch National MS Foundation, Merck for MS-related research & Merck for MS-related research |
Matni et al. (2022) [54] | 2019 | Lebanon | HDA -RMS patients | Assessing cost-utility and financial impact of cladribine tablets in HDA -RMS patients compared with other HDA-RMS therapies | CUA & budget impact model (A Markov state transition model) | Lebanese National Social Security Fund (NSSF) perspective | 50-year | The willingness to pay threshold of 22,000 USD (approximately three times the gross domestic product [GDP] per capita) per QALY | 3.5% | Deterministic sensitivity analysis, Probabilistic sensitivity analysis | High | Merck Serono Middle East FZ-Ltd, an affiliate of Merck KGaA, Darmstadt, Germany |
Spelman et al. (2022) [55] | 2019 | UK | 3935 Adults with highly active RRMS (HA-RRMS) with inadequate response to BRACETD (first line therapies) | The comparative effectiveness of switching to natalizumab or fingolimod or within BRACETD | CEA (published Markov structure with health states based on the Expanded Disability Status Scale) | UK third-partypayer perspective | Willingness-to-pay threshold of £30,000 per quality-adjusted life-year (QALY) gained | 3.5% | Three-way-multinomial-propensity-score–matched analysis | High | Biogen International GmbH (Baar, Switzerland); MSBase receives general financial support from Biogen, Genzyme, Merck (MSD), Merck Serono, Novartis, Roche, and Teva | |
Espinoza et al. (2021) [38] | 2018 | Chile | 261 Patients with HAD-RRMS | Cladribine compared with alemtuzumab, natalizumab, and ocrelizumab | CEA (Markov model) | Chilean health care public sector | 45 years | Equivalent to 3 GDP per capita | 3% | Deterministic & probabilistic sensitivity analysis | High | Merck S.A., Chile (a business of Merck KGaA, Darmstadt, Germany), commissioned to Pontificia Universidad Católica (Santiago, Chile) |
Bohlega et al. (2021) [56] | - | Kingdom of Saudi Arabia | Patients with high disease activity compared with other HDA-RRMS therapies | Cladribine tablets versus other DMDs (alemtuzumab, dimethyl fumarate, fingolimod, interferon beta-1a (subcutaneous and intramuscular) and beta-1b, natalizumab, and teriflunomide) in the treatment of HDA-RRMS | CEA (Markov state transition model), | Kingdom of Saudi Arabia payer’s perspective | 50-year | The willingness-to-pay threshold of Saudi Riyal (SAR) 225 326 (approximately 3 times of gross domestic product per capita) per QALYs gained | 3.5% | One-way & probabilistic Sensitivity analysis | High | Merck Serono Middle East FZ-Ltd, an affiliate of Merck KGaA, Darmstadt, Germany |
Ayati et al. (2021) [43] | 2019 | Iran | Iranian patients with relapsing multiple sclerosis | Ocrelizumab in comparison to natalizumab | CUA (A 31-health-state Markov model) | Societal perspective | 10 years | Iran’s pharmacoeconomic WTP threshold ($2709) | Costs: 7.2% and QALYs: 3.5% | Deterministic sensitivity analysis and probabilistic sensitivity analysis | High | Roche Corporation, Roche Pars Ltd |
Ayati et al. (2021) [44] | 2020 | Iran | Patients with HDA-RMS as on and off-treatment | Cladribine tablets compared to natalizumab | CEA (A 5-year cohort-based Markov model) | Societal perspective | 5 years | WTP threshold of 1 to 3 gross domestic product (GDP) per capita | 3.5% | Deterministic sensitivity analysis and probabilistic sensitivity analysis | High | None |
Lasalvia et al. (2020) [57] | 2016 | Colombia | Highly active RRMS patients | Natalizumab Compared With Fingolimod | CEA (Markov economic model) | Colombian healthcare system perspective | 5 years | 3 times the gross domestic product per capita of Colombia, equivalent to $17 401 | 5% | Univariate and probabilistic sensitivity analysis | High | Stendhal |
Poveda et al. (2019) [39] | 2018 | Spain | Patients with RMS with high disease activity | Cladribine Tablets compared with fingolimod | CEA (Markov model) | National Health System | 50 years | - | 3% | Deterministic and probabilistic sensitivity analyzes | High | Merck, S.L.U., an affiliate of Merck KGaA Darmstadt, Germany |
Dembek et al. (2014) [27] | 2010 | Spain | 1,000 RRMS patients | Injectable DMTs (interferon beta-1a (SC IFNb-1a), interferon beta-1b (IFNb-1b) and glatiramer acetate (GA)) for the first-line treatment | CEA (Markov model) | Societal perspective | 30 years | - | 3% | Univariate and probabilistic sensitivity analyses | High | Biogen Idec |
Ginestal et al. (2023) [61] | Unit costs: 2021, Cost of the drugs: 2022 | Spain | RRMS patients | Cost–effectiveness of cladribine tablets and dimethyl fumarate | CEA (probabilistic Markov model (second-order Monte Carlo simulation)) | Spanish National Health System perspective | 10 years | WTP of 25,000€ per QALY gained | 3% | Univariate sensitivity analyses | High | Merck, S.L.U., Madrid, Spain |
Furneri et al. (2019) [28] | 2015 (in Euro) | Italy | RRMS patients | Early escalation to natalizumab vs. switching among immunomodulators, followed by late escalation to natalizumab, in patients affected by RRMS | CEA (Markov model) | Italian societal perspective | Over a 50 year | Willingness to pay threshold of € 50,000 per QALY gained | 3.50% | Univariate deterministic and probabilistic sensitivity analyses | High | Biogen Italy (Milan, Italy) |
Cortesi et al. (2022) [60] | 2020 | Italy | Patients with secondary progressive multiple sclerosis (SPMS) | The siponimod cost-effectiveness profile and its relative budget impact compared with other DMTs, | CEA (A cohort-based multi-state Markov model) | Italian National Healthcare System perspective | Life-time horizonand 1-year cycle | WTP of €40,000 per QALY gained | 3% | One-way sensitivity analysis and probabilistic sensitivity analysis | High | Novartis SpA |
Stanisic et al. (2019) [34] | 2017 | Italy | Patients with RRMS | Alemtuzumab in comparison with subcutaneous IFN β-1a, natalizumab and fingolimod | CEA (Markov model) | Payer perspective | Lifetime horizon (i.e 50 years) | WTP threshold in Italy (€40,000/QALY) | 3.5% | Deterministic one-way sensitivity analysis and probabilistic sensitivity analyses | High | Sanofi SpA |
Montgomery et al. (2022) [58] | 2020 | UK | Patients with active secondary progressive multiple sclerosis | Oral siponimod versus continued oral or infused relapsing–remitting multiple sclerosis disease-modifying therapies | CEA (cohort Markov model) | UK National Health Service perspective | 1 year | WTP threshold of £30,000/QALY | 3.5% | Probabilistic and deterministic sensitivity analyses | High | Novartis Pharmaceuticals UK Ltd |
Rezaee et al. (2022) [29] | 2019 | Iran | 120 patients with RRMS | Rituximab against natalizumab | CEA (Markov model) | Societal perspective | Over 1 year | $ 37,641 (3* GDP) | Costs = 5.8 & Outcomes = 3% | One-way sensitivity analysis and Probabilistic Sensitivity Analysis | High | Shiraz University of Medical Sciences |
Becker et al. (2011) [47] | 2009 | US | Patients with RRMS | The impact of selecting the 2-year cohort rather than the all-patient cohort for IM IFNβ-1a on the results of the original model | CEA | Health care payer perspective | 2 years | - | - | Sensitivity analysis | High | Biogen Idec Inc |
Kantor (2023) [48] | 2020 | US | Patients with RRMS | Ozanimod compared with teriflunomide, interferon beta-1a, interferon beta-1b, glatiramer acetate, fingolimod, and dimethyl fumarate | CEA | - | Over 1 year | - | - | Sensitivity analysis | Fair | Bristol Myers Squibb |
Baharnoori et al. (2022) [13] | 2021 | Canada | Adults with RRMS | Ofatumumab | CEA (Markov cohort model) | Canadian healthcare system perspective | 25 years | WTP threshold of $50,000 Canadian dollars (CAD) per QALY gained | 1.5% | Probabilistic sensitivity analysis | High | Novartis Pharmaceutical Canada Inc |
Lazzaro et al. (2022) [40] | 2019 | Italy | RRMS naïve and 1000 RRMS experienced patients | To compare the costs and QALYs of teriflunomide in RRMS naïve patients vs. RRMS patients previously treated (experienced) with other DMTs (alemtuzumab; cladribine; fingolimod; natalizumab; ocrelizumab) | CUA (A four health states Markov model-supported cost-utility analysis) | Healthcare sector & societal perspective | 7 years | WTP = 0 per incremental QALY gained | 3% | One-way, scenario and probabilistic sensitivity analyses | High | Sanofi S.r.l |
Pinheiro et al. (2020) [45] | 2016 | Portugal | Patients with highly active RRMS | Cost-utility of cladribine tablets versus fingolimod | CEA & CUA (A 1-year cycle cohort-based Markov state transition model) | Payers’ perspective | 50 years | - | 5% | Probabilistic and deterministic sensitivity analyses | High | Merck S.A |
Martins et al. (2023) [33] | 2018 | Portugal | Treatment-naïve RMS, previously treated RMS, and PPMS patients | The clinical and econoemmic impact of ocrelizumab relative to current clinical practice, including interferon β-1a, dimethyl fumarate, glatiramer acetate, teriflunomide, fingolimod, and natalizumab | CEA (Markov model) | Societal perspective | A lifetime time-horizon with annual cycles | -For the RMS population: WTP greater or equal to €18,000/QALY -For the PPMS population: WTP values higher than €81,000/QALY | 5% | Scenario analysis and probabilistic sensitivity analysis | High | Roche Farmaceutica e Quimica, Lda., Portugal |
AlRuthia et al. (2021) [49] | - | Saudi Arabia | 146 patients with RRMS | Comparing the cost-effectiveness of orally administered medications (e.g., fingolimod, dimethyl fumarate, and teriflunomide), interferon (IFN)-based therapy, and monoclonal antibodies (MABs) (e.g., natalizumab and rituximab) | CEA | Public healthcare payer perspective | At least 1 year | - | - | - | Poor | King Saud University, Riyadh, Saudi Arabia |
Versteegh et al. (2022) [19] | 2019 | Netherlands | 382 Dutch patients with MS | Effectiveness and Cost-Effectiveness of 360 DMTES in MS | CEA (microsimulation model) | Societal perspective | Lifetime | €50 000 per QALY | Effects: 1.5% & costs: 4% | Probabilistic sensitivity analyses | High | The Erasmus University Medical Center |
Nakhaipour et al. (2020) [59] | 2018 | Canada | Patients aged 10 years and above with RMS | The incremental cost-effectiveness of fingolimod versus IFN β-1a | CEA (discrete-time Markov model) | Canadian health care system | 2 years | WTP threshold of Canadian dollars (CAD) 50,000 per quality-adjusted life-year | 1.5% | One-way sensitivity analysis and probabilistic sensitivity analysis | High | Novartis Pharmaceuticals Canada Inc., Dorval, Quebec, Canada |
Schur et al. (2021) [30] | 2020 | Switzerland | Adult patients with secondary progressive multiple sclerosis (SPMS) with active disease | The cost effectiveness and budget impact of siponimod compared to interferon beta-1a | CEA (Markov model) | Swiss health insurance perspective | A cycle length of 1 year and life-long time horizon | A WTP threshold of CHF 100,000 per QALY gained | 3% | One-way deterministic and probabilistic sensitivity analyses | High | Novartis Pharma Schweiz AG |
Alharbi et al. (2023) [62] | 2022 | Saudi Arabia | 93 RRMS | Comparing the direct medical cost and consequences between rituximab and natalizumab in managing RRMS, and exploring the cost and consequence of ocrelizumab in managing RRMS as a second-choice treatment | - | Public healthcare institutions | 6 months | - | - | - | Fair | King Saud University, Riyadh, Saudi Arabia |
Gani et al. (2008) [22] | 2005 | UK | 2048 MS patients | Natalizumab compared with interferon-β, glatiramer acetate and best supportive care | CEA (Markov model) | UK societal cost perspective | 30 years | £36,000 per QALY | 3.5% | Univariate sensitivity analysis | High | Biogen Idec Ltd |
Chilcott, et al. (2003) [2] | - | UK | Patients with RRMS and SPMS | Four disease-modifying treatments: interferon betas, glatiramer acetate for relapsing–remitting and interferon betas, glatiramer acetate for secondary progressive multiple | CEA | UK National Health Service | 20 years | £20 000 | Discounted costs at 6% per annum, the discounted quality of life benefits at 1.5% per annum | Multivariate Monte Carlo sensitivity analysis | High | National Institute for Clinical Excellence |
Chevalier et al., (2016) [17] | 2015 | France | 1,000 patients | Glatiramer acetate, IFNbeta-1a 30mcg intramuscularly and 44mcg subcutaneously, IFN beta-1b 250mcg and teriflunomide as first-line therapies and fingolimod and natalizumab, as second-line therapies | CEA (cohort-based Markov model) | Payer and societal | 30 years | - | 4% per annum during the first 30 years and2% after as requested by the French guidelines | Univariate and probabilistic | High | Biogen France SAS |
Chanatittarat, et al. (2018) [35] | 2016 | Thailand | 105 MS patients (mean age 37.8 years) | Best supportive care (BSC), fingolimod, IFNβ − 1b, and IFNβ − 1a | CUA (Markov model) | Societal | Month cycle length, lifetime horizon or 30 years | WTP threshold of USD 4,500 per QALY gained | 3 percent, Costs were converted to USD using 2016 average annual exchange rate of 35.26 Thai baht (THB) per 1 USD | Univariate and probabilistic | High | None |
Brown, et al. (2000) [52] | 1999 | Canada/ Nova Scotia | 1,000 females and 1,000 males followed 40 years | interferon beta-1b (IFN¯-1b) | CEA (simulation model) | Ministry of health (MOH) | Unspecified lifespan | - | 5% | Sensitivity analysis (the cumulative probabilities) | High | Canadian Coordinating Office for Health Technology Assessment (CCOHTA) |
Bozkaya, et al. (2017) [23] | 2016 | USA | for relapsing–remitting multiple sclerosis (RRMS) | natalizumab (NTZ), dimethyl fumarate (DMF), and peginterferon beta-1a (PEG) with fingolimod (FIN), glatiramer acetate (GA, 20 mg daily), and subcutaneous interferon beta-1a (IFN, 44 mcg), | CEA (Markov Model) | Third-party payer | Three-month cycles were modeled over a 10-year time horizon | - | 3% | One-way deterministic sensitivity analysis | High | Biogen |
Alsaqa’aby, et al. (2017) [24] | 2015 | Saudi Arabia (Tertiary care hospital) | 1000 RRMS patients (for more than 400real MS patients) | Oral agents v (fingolimod, teriflunomide, dimethyl fumarate,) vs. interferon (IFN)-b1 | CEA: Cohort Simulation Model (Markov Model( | Saudi Payer | 20 years and an annual cycle length | $100,000 | 3%, All costs were reported in Saudi Riyals (SAR) and converted into the equivalent value of 2015 US dollars | One-way and probabilistic (A probabilistic sensitivity analysis based on a second-order Monte Carlo simulation (1000 times)) | High | None |
Hernandez, et al. (2016) [18] | 2014 | USA | RRMS and includes adult patients. The population is 29.2% male with a mean age of 36.5 years | Peginterferon beta-1a compared with interferon beta-1a and glatiramer acetate | CEA( Markov cohort model) | US payer | over 10 years | $50,000 | 3% | Probabilistic sensitivity analysis | High | Biogen |
Hernandez, et al. (2017) [25] | 2015 | Scotland | RRMS | Peginterferon beta-1a and Interferon beta-1a 30 mcg and Interferon beta-1a 22 mcg and Interferon beta-1a 44 mcg and Interferon beta-1b and Glatiramer acetate 20 mg | CEA (Markov cohort model) | National Health Service and Personal Social Services | over 30 years | £20,000 per QALY | and discounted at 3.5% per year | Probabilistic sensitivity analysis | High | Biogen |
Sawad, et al. (2017) [63] | 2014 | USA | patients with RRMS Healthcare costs data were obtained from a study conducted in 2004 by Kobelt et al. assessing the cost of MS disease by stratified EDSS health states | Strategy 1: (symptom management [SM] alone), vs. Strategy 2: (SM and IFN-β-1a), vs. Strategy 3:(SM and natalizumab) vs. Strategy 4: (SM and alemtuzumab) | CEA (Markov model) | Third-party payer | Over 20 years | $100,000 WTP threshold per QALY | 1- All costs were inflated to 2014 US$ by using the US\ 2- costs were discounted using an annual discount rate of 3% | One-way, Probabilistic sensitivity analysis (second-order Monte Carlo simulation | High | None |
Hashemi-Meshkini A, et al. (2018) [26] | 2016 | Iran | 1,000 patients with relapsing–remitting MS (RRMS) | Pegylated versus non-pegylated interferon beta 1a | CEA (Markov model) | payer perspective (patients and third-party payers) | One-month cycles over 10 years | 15,945 USD | Cost discount rate (5%), Utility discount rate (3%) | One-way deterministic sensitivity analysis | High | None |
Michels, et al. (2019) [32] | 2016–2017 | Netherlands | Derived from a meta-analysis study (113 for cladribine group) | Cladribine tablets vs. alemtuzumab and fingolimod | CEA | Societal | Unspecified lifespan | €50,000/QALY gained | 4% for costs and 1.5% for outcomes | Deterministic and probabilistic sensitivity analysis | High | Merck B. V group |
Imani, et al. (2012) [36] | 2011 | Iran | Model-based- population is not clear | Symptom Management vs. Avonex, Betaferon, Rebif, CinnoVex | CUA (Markov model) | Healthcare | Unspecified lifespan | US$50,000/QALY gained | 7.2% annually | Sensitivity analysis | High | Tabriz University of Medical Sciences |
Janković, et al. (2009) [31] | 2009 | Serbia | Model-based—the population is not clear | Symptom management alone vs combination with subcutaneous glatiramer acetate (SC GA), subcutaneous interferon β-1a (SC IFNβ-1a), intramuscular interferon β-1a (IM IFNβ-1a), or subcutaneous interferon β-1b (SC IFNβ-1b) | CEA | Societal | lifetime (40 years) | WTP 5,000,000.00 RSD | 3% annually | Multiple univariate sensitivity | High | Serbian Ministry of Science and Ecology |
Maruszczak, et al. (2015) [41] | 2013–2014 | UK | Derived from a systematic review- the population is not clear | fingolimod vs. dimethyl fumarate (DMF) | CUA (cohort Markov model) | NHS and Personal Social Services | Lifetime (50 years) | £20,000 and £30,000/QALY | 3.5% for both costs and benefits | Deterministic & Probabilistic sensitivity analysis | High | Novartis Pharmaceuticals UK Ltd, Camberley, UK |
16.Mantovan et al. (2019) [42] | Euros inflated to June 2018 | Italy | Cohort and RCT based, the number of 1237 patients | Dimethyl fumarate vs. other first-line alternatives | CEA (Markov model) | Societal | Lifetime (50 years) | € 50,000 per QALY gained | 3.5% for both costs and outcomes | Univariate deterministic and multivariate probabilistic | High | Biogen Italia (Milan, Italy) |
Najafi, et al. (2015) [50] | 2012 | Iran | 140 patients | Avonex vs. CinnoVex | CEA | Ministry of Health and Medical Education | 1 year | Not clear enough | Not used | Two-way sensitivity analysis | High | Iran University of Medical Sciences (IUMS) |
Nuijten, et al. (2002) [46] | 1998 | UK | The number of 560, 372, & 358 patients based on the previous three RCTs | Preventive treatment with interferon beta, No preventive treatment | CEA & CUA (lifetime Markov process model) | Third-party payer & Societal | Lifetime (25 years) | - | 6% annually | Univariate sensitivity analyses | High | None |
Soini, et al. (2017) [10] | 2014 | Finland | 713 patients | DMF 240 mg PO BID, teriflunomide 14 mg once daily, GA 20 mg SC once daily, IFN-β1a 44 mg SC TIW, IFN-β1b 250 mg SC EOD, IFN-β1a 30 mg IM QW, best supportive care (BSC)- placebo | CEA/CBA (cohort Markov model) | Finnish payer perspective and Scenario analysis with a societal perspective | 15 years | € 68,000 per QALY gained | 3% annually | Probabilistic sensitivity analysis | High | Sanofi Genzyme |
Su, et al. (2016) [64] | 2013 Canadian dollars | Canada | Cohort and trial based 308 patients | DMF, Glatiramer Acetate (GA), Rebif (Interferon-b 1a SC) 44 mcg | CEA (Markov cohort model) | Ministry of Health | Lifetime (20 years) | Canada ($50 000–60 000) | 5% for both health and economic outcomes | One-way and probabilistic sensitivity analyses | High | Biogen |
Zhang, et al. (2014) [51] | Inflated to 2012 dollars | USA | A cohort of 1,000 patients | Fingolimod, Teriflunomide, dimethyl fumarate, intramuscular (IM) interferon (IFN)-b1a | CBA/CEA (Markov model) | Societal | 5 years | US$ 150,000 per (QALY) | 3% annually | One-way and probabilistic sensitivity analysis | High | None |
Zimmermann et al., (2018) [37] | 2017 | US | Treatment-naïve adults with RRMS or PPMS | DMTs for RRMS (first-line: dimethyl fumarate, glatiramer acetate, interferon β-1a, interferon β-1b, peginterferon β-1a, teriflunomide, natalizumab, fingolimod, and ocrelizumab; second-line: alemtuzumab, natalizumab, fingolimod, and ocrelizumab), ocrelizumab for PPMS, and supportive care | CUA ( Markov model) | US payer perspective | One year | $150,000 | 3% annually | One-way and probabilistic sensitivity analyses | High | The Institute for Clinical and Economic Review |