Cost-effectiveness of treatment sequences following first-line rituximab in relapsing-remitting multiple sclerosis: a Norwegian microsimulation study

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.