ObjectiveThe prevailing approaches to selecting multiple sclerosis (MS) disease modifying therapies (DMTs) have contributed to exponential increases in societal expenditures and out‐of‐pocket expenses, without compelling evidence of improved outcomes. Guidance is lacking regarding when and in whom the benefits of preventing MS‐related disability likely outweighs the risks of highly effective DMTs (HET) and when it is appropriate to consider DMT costs. Our objective was to develop a standardized approach to improve the quality, affordability and equity of MS care.MethodsMS experts partnered with health plan pharmacists to develop an ethical, risk‐stratified, cost‐sensitive treatment algorithm. We developed a risk‐stratification schema to classify patients with relapsing forms of MS as high, intermediate or low risk of disability based on the best available evidence and, when the evidence was poor or lacking, by consensus. DMTs are grouped as highly, modestly or low/uncertain effectiveness and preferentially ranked within groups by safety based on pre‐specified criteria. We reviewed FDA documents and the published literature. When efficacy and safety are equivalent, the lower cost DMT is preferred.ResultsAssignment to the high‐risk group prompts treatment with preferred HETs early in the disease course. For persons in the intermediate‐ or low‐risk groups with cost or health care access barriers, we incorporated induction therapy with an affordable B‐cell depleting agent. Based on more favorable safety profiles, our preferred approach prioritizes use of rituximab and natalizumab among HETs and interferon‐betas or glatiramer acetate among modestly effective agents.InterpretationThe risk‐stratified treatment approach we recommend provides clear, measurable guidance in whom and when to prescribe HETs, when to prioritize lower cost DMTs and how to accommodate persons with MS with cost or other barriers to DMT use. It can be adapted to other cost structures and updated quickly as new information emerges. We recommend that physician groups partner with health insurance plans to adapt our approach to their settings, particularly in the United States. Future studies are needed to resolve the considerable uncertainty about how much variability in prognosis specific risk factors explain.
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