Frontiers in neurology · 2026
Cost-effectiveness of treatment sequences following first-line rituximab in relapsing-remitting multiple sclerosis: a Norwegian microsimulation study.
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Huygens Simone, Versteegh Matthijs, Berg-Hansen Pål, Bjelland Stein Henry, Holmøy Trygve, Torkildsen Øivind
Аннотация
BACKGROUND: The Norwegian guideline recommends highly effective disease-modifying therapies (DMTs) as the first line treatment for multiple sclerosis (MS), with rituximab preferred in clinical practice. While rituximab is effective, patients may discontinue due to side-effects or develop disease activity. Limited guidance exists on optimal switches following first line rituximab.
OBJECTIVES: To estimate the costs and effects of different treatment sequences following first line rituximab in relapsing remitting MS patients in Norway.
DESIGN: A microsimulation model adapted to the Norwegian setting estimated outcomes for different treatment sequences following first line rituximab. Four neurologists were interviewed using a structured expert elicitation tool to inform switching behavior. The model allowed for three treatment lines after rituximab, with switches possible to fingolimod, ponesimod, cladribine tablets, or natalizumab.
METHODS: The model simulated all 32 possible treatment sequences and calculated costs per quality adjusted life year (QALY) according to Norwegian pharmacoeconomic guidelines.
RESULTS: Neurologists were more likely to switch patients with >1 relapse (78%) or relapse and disability progression (66%) versus one relapse (54%). The most cost-effective sequence after rituximab is cladribine tablets (line 2), ponesimod (line 3), and natalizumab (line 4). The probability that second line cladribine tablets are most cost-effective is >75%. Mean time on first line rituximab was 15.2 years. The model predicts that over lifetime 21% of patients would require a fourth line of treatment due to the cumulative effects of discontinuation and recurring disease activity triggering treatment switches.
CONCLUSION: Patients on first line rituximab may require a treatment switch due to side-effect induced discontinuation or new disease activity. If a switch from rituximab to another DMT is the preferred clinical course of action, this study showed that it is most cost-effective to switch to cladribine tablets followed by ponesimod and natalizumab.
OBJECTIVES: To estimate the costs and effects of different treatment sequences following first line rituximab in relapsing remitting MS patients in Norway.
DESIGN: A microsimulation model adapted to the Norwegian setting estimated outcomes for different treatment sequences following first line rituximab. Four neurologists were interviewed using a structured expert elicitation tool to inform switching behavior. The model allowed for three treatment lines after rituximab, with switches possible to fingolimod, ponesimod, cladribine tablets, or natalizumab.
METHODS: The model simulated all 32 possible treatment sequences and calculated costs per quality adjusted life year (QALY) according to Norwegian pharmacoeconomic guidelines.
RESULTS: Neurologists were more likely to switch patients with >1 relapse (78%) or relapse and disability progression (66%) versus one relapse (54%). The most cost-effective sequence after rituximab is cladribine tablets (line 2), ponesimod (line 3), and natalizumab (line 4). The probability that second line cladribine tablets are most cost-effective is >75%. Mean time on first line rituximab was 15.2 years. The model predicts that over lifetime 21% of patients would require a fourth line of treatment due to the cumulative effects of discontinuation and recurring disease activity triggering treatment switches.
CONCLUSION: Patients on first line rituximab may require a treatment switch due to side-effect induced discontinuation or new disease activity. If a switch from rituximab to another DMT is the preferred clinical course of action, this study showed that it is most cost-effective to switch to cladribine tablets followed by ponesimod and natalizumab.