OBJECTIVES

A growing number of treatments is available for managing relapsing remitting multiple sclerosis (MS). Patients are typically exposed to more than one treatment over their lifetime, but optimal sequences have never been investigated. This study identifies the sequence of treatments that yields most health benefit for money in The Netherlands.

METHODS

A microsimulation model with a lifetime time horizon and a societal perspective evaluated the cost-effectiveness of 445 potential treatment sequences. Sequences were limited to treatments in the Dutch MS clinical guidelines with first line (interferons, glatiramer acetate, dimethyl fumarate and teriflunomide), second line (fingolimod, ocrelizumab, cladribine and natalizumab) and third line (alemtuzumab). Conversion to secondary progressive MS was included. An induction strategy with natalizumab or ocrelizumab as first line treatment was also evaluated. Effectiveness of treatments in reducing relapses and disease progression were captured in network meta-analyses. Sequences were ranked with net health benefit and fully incremental analyses.

RESULTS

All treatment sequences were cost-effective relative to ‘no treatment’. Out of 445 treatment sequences, 430 were dominated, 7 were extendedly dominated and 3 of 8 non-dominated were cost-effective. The highest net health benefit was achieved by a sequence that commences with interferon, includes cladribine and ocrelizumab in the second line and has alemtuzumab as a final rescue alternative. Including societal costs had limited impact on outcomes. The net health benefit method and the fully incremental method did not fully align on the optimal treatment sequence.

CONCLUSIONS

All MS treatment sequences are cost-effective relative to no treatment. Treatments that were dominated in the fully incremental analysis ranked high in a net health benefit analysis. Limitations of the study include the lack of treatment effect on imaging results, which are an important driver in clinical decision making, and issues inherent to the use of NMA, such as confounders due to trial design.