{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T18:27:33Z","timestamp":1788546453238,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T00:00:00Z","timestamp":1615334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The prevailing approaches to selecting multiple sclerosis (MS) disease modifying therapies (DMTs) have contributed to exponential increases in societal expenditures and out\u2010of\u2010pocket expenses, without compelling evidence of improved outcomes. Guidance is lacking regarding when and in whom the benefits of preventing MS\u2010related 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MS experts partnered with health plan pharmacists to develop an ethical, risk\u2010stratified, cost\u2010sensitive treatment algorithm. We developed a risk\u2010stratification 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\u2010specified criteria. We reviewed FDA documents and the published literature. When efficacy and safety are equivalent, the lower cost DMT is preferred.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Assignment to the high\u2010risk group prompts treatment with preferred HETs early in the disease course. For persons in the intermediate\u2010 or low\u2010risk groups with cost or health care access barriers, we incorporated induction therapy with an affordable B\u2010cell depleting agent. Based on more favorable safety profiles, our preferred approach prioritizes use of rituximab and natalizumab among HETs and interferon\u2010betas or glatiramer acetate among modestly effective agents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>The risk\u2010stratified 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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51326","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T12:06:57Z","timestamp":1615378017000},"page":"980-991","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Improving quality, affordability, and equity of multiple sclerosis care"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6891-7147","authenticated-orcid":false,"given":"Annette","family":"Langer\u2010Gould","sequence":"first","affiliation":[{"name":"Department of Neurology Los Angeles Medical Center Southern California Permanente Medical Group Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa","family":"Klocke","sequence":"additional","affiliation":[{"name":"Department of Neurology Clinical Pharmacy Colorado Permanente Medical Group Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Beaber","sequence":"additional","affiliation":[{"name":"Department of Neurology Downey Medical Center Southern California Permanente Medical Group Downey California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonu M.","family":"Brara","sequence":"additional","affiliation":[{"name":"Department of Neurology Panorama City Medical Center Southern California Permanente Medical Group Panorama City California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Debacker","sequence":"additional","affiliation":[{"name":"Department of Neurology Los Angeles Medical Center Southern California Permanente Medical Group Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluwasheyi","family":"Ayeni","sequence":"additional","affiliation":[{"name":"Department of Neurology Glenlake Medical Center The Southeast Permanente Medical Group Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen S.","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Neurology Fontana Medical Center Southern California Permanente Medical Group Fontana California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,10]]},"reference":[{"key":"e_1_2_17_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.7625"},{"key":"e_1_2_17_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31828aab14"},{"key":"e_1_2_17_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.2711"},{"key":"e_1_2_17_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458518765656"},{"key":"e_1_2_17_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2019.07.021"},{"key":"e_1_2_17_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000960"},{"key":"e_1_2_17_8_1","volume-title":"AHRQ Comparative effectiveness reviews. 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