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. 2025 Jan 17;272(2):153.
doi: 10.1007/s00415-024-12723-4.

Cost-consequence analysis of early vs. delayed natalizumab use in highly active relapsing-remitting multiple sclerosis: a simulation study

Hernan Inojosa #  1 , Dirk Schriefer #  1 , Nils-Henning Ness  2 , Anja Dillenseger  1 , Katja Akgün  1 , Tjalf Ziemssen  3
Affiliations

Cost-consequence analysis of early vs. delayed natalizumab use in highly active relapsing-remitting multiple sclerosis: a simulation study

Hernan Inojosa et al. J Neurol. .

Abstract

Background: Natalizumab (NAT) is an established disease-modifying therapy (DMT) for highly active multiple sclerosis (MS). However, its use involves complex decision-making, often leading to initial use of lower efficacy therapies. Recently, the first biosimilar NAT was approved, enabling competitive pricing. This study assessed the societal implications of initiating NAT in various scenarios through a cost-consequence analysis.

Methods: A 10-year Markov model based on the Expanded Disability Status Scale (EDSS) was employed, with 11 health states, annual cycles, and half-cycle correction. The cohort had an initial age of 36 years and 70% females. NAT was compared to common initial therapies (glatiramer acetate, teriflunomide, dimethyl fumarate, and fingolimod). Scenarios included continuous use, early (after 1 year), and delayed (5 years) switch to NAT. Baseline characteristics and probabilities for clinical and economic outcomes were derived from clinical trial data, published literature, and other available sources.

Results: Continuous NAT use resulted in the highest time spent on low EDSS levels, fewer relapses, reduced years of life lost due to disability, and a higher employment rate over a 10-year period. Switching to NAT after 1 year yielded outcomes similar to continuous NAT use. Despite higher DMT costs, disease management costs, including indirect costs and non-DMT direct medical costs, were lower in continuous use and early switch to NAT. Late switching resulted in outcomes most comparable to continuous use of the initial DMT.

Conclusion: Continuous and early switch to NAT resulted in better clinical outcomes and lower societal economic burden compared to delayed NAT initiation, indicating potential long-term cost savings.

Keywords: Cost–consequence; Economic evaluation; Health economics; Markov model; Multiple sclerosis; Treatment strategies.

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Conflict of interest statement

Declarations. Conflicts of interest: HI received speaker honoraria from Roche and financial support for research activities from Teva, Biogen, and Alexion. N-HN is an employee of Hexal AG. K.A. received personal compensation from Novartis, Biogen Idec, Teva, Sanofi, and Roche for consulting services. TZ reports scientific advisory board and/or consulting for Biogen, Roche, Novartis, Celgene, and Merck; compensation for serving on speakers bureaus for Roche, Novartis, Merck, Sanofi, Celgene, and Biogen; and research support from Biogen, Novartis, Merck, and Sanofi. DS and AD have nothing to declare. Ethical approval: This article does not contain any studies with human participants or animals performed by any of the authors.

Figures

Fig. 1
Fig. 1
Patient time (in percent) spent in the health states over a 10-year horizon according to DMT and timing of treatment initiation. NAT natalizumab, FTY fingolimod, DMF dimethyl fumarate, TER teriflunomide, GA glatiramer acetate
Fig. 2
Fig. 2
Proportion of people with MS reaching EDSS 7 or higher over a 10-year horizon according to DMT and timing of treatment initiation. NAT natalizumab, GA glatiramer acetate, TER teriflunomide, DMF dimethyl fumarate, FTY fingolimod
Fig. 3
Fig. 3
Average EDSS over a 10-year horizon according to DMT and timing of treatment initiation. NAT natalizumab, GA glatiramer acetate, TER teriflunomide, DMF dimethyl fumarate, FTY fingolimod
Fig. 4
Fig. 4
Proportion of employed pwMS over a 10-year period according to DMT and timing of treatment initiation. NAT Natalizumab, GA glatiramer acetate, TER teriflunomide, DMF dimethyl fumarate, FTY fingolimod
Fig. 5
Fig. 5
Cost outcomes after a 10-year period according to DMT and timing of treatment initiation. Relapse costs are presented separately in Fig. 6. *Direct medical costs and medication costs excluding DMT-related expenses. Associated DMT-related costs are presented separately in (e) and incorporated into the calculation of total costs (f). NAT natalizumab, FTY fingolimod, DMF dimethyl fumarate, TER teriflunomide, GA glatiramer acetate
Fig. 6
Fig. 6
Annual relapse costs after a 10-year period according to DMT and timing of treatment initiation. It is unclear to what extent relapse costs were incorporated into the referenced input data sources utilized for disease management costs. Therefore, to prevent an overestimation of the aggregated costs illustrated in Fig. 5, relapse costs are presented separately. NAT natalizumab, FTY fingolimod, DMF dimethyl fumarate, TER teriflunomide, GA glatiramer acetate
Fig. 7
Fig. 7
Univariate sensitivity analysis. Incremental costs after increase (white) or decrease (black) in 10% of respective variables are presented for 10 years NAT vs. 10 years of each selected DMT. Costs are presented in 2024 euros. ARR annualized relapse ratio, 6-CDP 6-month confirmed disability progression, NAT natalizumab, GA glatiramer acetate, TER teriflunomide, DMF dimethyl fumarate, FTY fingolimod
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