{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T15:42:29Z","timestamp":1782142949506,"version":"3.54.5"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T00:00:00Z","timestamp":1693958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background and objectives<\/jats:title><jats:p>While randomized, controlled trials (RCTs) are the gold standard for determining treatment efficacy, they do not capture the effectiveness of treatment during real-world use. We aimed to evaluate the association between demographics and multiple sclerosis (MS) disease-modifying therapy (DMT) exposure, including treatment adherence and switches between different DMTs, on the risk of subsequent MS relapse.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>All persons with relapsing-onset MS (pwRMS) living in Manitoba between 1999 and 2014 were identified from provincial healthcare databases using a validated case definition. Use of DMTs was abstracted from the provincial drug database covering all residents of Manitoba, including use of any DMT, stopping\/starting any DMT, switches between different DMTs and adherence as defined by cumulative medication possession ratios (CUMMPRs) of 50, 70, 80 and 90%. Time to first-treated relapse was used as the outcome of interest in logistic regression and Cox-proportional hazards regression models adjusting for demographic covariates including age and year of diagnosis, sex, socioeconomic status and number of medical comorbidities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>1780 pwRMS were identified, including 1,510 who were on DMT at some point in the study period. While total DMT exposure was not associated with the time to subsequent treated relapse, individuals who switched between more than 2 DMTs had higher post-switch rates of relapse. Switching to second-line DMTs was associated with a longer time to treated relapse in comparison to those who remained on a first-line DMT (HR 0.44; 95%CI: 0.32\u20130.62, <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Switching to high-efficacy DMTs reduces the rates of subsequent MS relapse at the population level.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2023.1243589","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T16:03:59Z","timestamp":1694016239000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Switching to second line MS disease-modifying therapies is associated with decreased relapse rate"],"prefix":"10.3389","volume":"14","author":[{"given":"James John","family":"Marriott","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Okechukwu","family":"Ekuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall","family":"Fransoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth Ann","family":"Marrie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1212\/WNL.0000000000002471","article-title":"For the attendees of the international workshop on comorbidity in multiple sclerosis","volume":"86","author":"Marrie","year":"2016","journal-title":"Chall Comorb Clin Trials Mult Sclerosis"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1136\/jnnp-2018-319831","article-title":"Comparison of Fingolimod, dimethyl fumarate and Teriflunomide for multiple sclerosis","volume":"90","author":"Kalincik","year":"2019","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1007\/s40801-021-00251-w","article-title":"Retrospective claims analysis of treatment patterns, relapse, utilization, and cost among patients with multiple sclerosis initiating second-line disease-modifying therapy","volume":"8","author":"Freeman","year":"2021","journal-title":"Drugs Real World Outcomes"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"2203","DOI":"10.3390\/ijerph19042203","article-title":"Adherence to therapy in patients with multiple sclerosis\u2014review","volume":"19","author":"Ko\u0142tuniuk","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1080\/19466315.2014.920275","article-title":"Estimation of drug effectiveness by modeling three time-dependent covariates: an application to data on Cardioprotective medications in the chronic Dialysis population","volume":"6","author":"Phadnis","year":"2014","journal-title":"Stat Biopharm Res"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1212\/01.WNL.0000096175.39831.21","article-title":"Effect of relapses on development of residual deficit in multiple sclerosis","volume":"61","author":"Lublin","year":"2003","journal-title":"Neurology"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/1472-6963-3-17","article-title":"Cost of managing an episode of relapse in multiple sclerosis in the United States","volume":"3","author":"O'Brien","year":"2003","journal-title":"BMC Health Serv Res"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1212\/WNL.0b013e3181cf6ec0","article-title":"The rising prevalence and changing age distribution of multiple sclerosis in Manitoba","volume":"74","author":"Marrie","year":"2010","journal-title":"Neurology"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.msard.2017.11.022","article-title":"Validation of an algorithm to detect severe MS relapses in administrative health databases","volume":"19","author":"Marriott","year":"2018","journal-title":"Mult Scler Relat Disord"},{"key":"ref10","first-page":"398","article-title":"Population-based use of mental health services and patterns of delivery among family physicians, 1992 to 2001","volume":"50","author":"Watson","year":"2005","journal-title":"Can J Psychiatr"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2112","DOI":"10.1212\/wnl.0000000000000495","article-title":"Intensive care unit admission in multiple sclerosis: increased incidence and increased mortality","volume":"82","author":"Marrie","year":"2014","journal-title":"Neurology"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.msard.2016.05.006","article-title":"Adherence and persistence to drug therapies for multiple sclerosis: a population-based study","volume":"8","author":"Evans","year":"2016","journal-title":"Mult Scler Relat Disord"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1177\/1352458516657440","article-title":"Determinants of non-adherence to disease-modifying therapies in multiple sclerosis: a cross-Canada prospective study","volume":"23","author":"McKay","year":"2017","journal-title":"Mult Scler"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.2147\/PPA.S138263","article-title":"Persistence to disease-modifying therapies for multiple sclerosis in a Canadian cohort","volume":"11","author":"Melesse","year":"2017","journal-title":"Patient Prefer Adherence"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1185\/03007995.2013.847411","article-title":"Comparative effectiveness of Fingolimod versus interferons or Glatiramer acetate for relapse rates in multiple sclerosis: a retrospective us claims database analysis","volume":"29","author":"Bergvall","year":"2013","journal-title":"Curr Med Res Opin"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"89","DOI":"10.2165\/11533330-000000000-00000","article-title":"Impact of adherence to interferons in the treatment of multiple sclerosis: a non-experimental, retrospective","volume":"30","author":"Steinberg","year":"2010","journal-title":"Cohort Study Clin Drug Invest"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s12325-010-0093-7","article-title":"Impact of adherence to disease-modifying therapies on clinical and economic outcomes among patients with multiple sclerosis","volume":"28","author":"Tan","year":"2011","journal-title":"Adv Ther"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"601","DOI":"10.3111\/13696998.2012.667027","article-title":"Impact of medication adherence to disease-modifying drugs on severe relapse, and direct and indirect costs among employees with multiple sclerosis in the us","volume":"15","author":"Ivanova","year":"2012","journal-title":"J Med Econ"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1001\/jamaneurol.2014.4147","article-title":"Comparison of switch to Fingolimod or interferon Beta\/Glatiramer acetate in active multiple sclerosis","volume":"72","author":"He","year":"2015","journal-title":"JAMA Neurol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1002\/acn3.180","article-title":"Comparative efficacy of switching to Natalizumab in active multiple sclerosis","volume":"2","author":"Spelman","year":"2015","journal-title":"Ann Clin Transl Neurol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e200005","DOI":"10.1212\/NXI.0000000000200005","article-title":"Disease-modifying drugs for multiple sclerosis and association with survival","volume":"9","author":"Ng","year":"2022","journal-title":"Neurol Neuroimmunol Neuroinflamm Sep"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"794075","DOI":"10.3389\/fimmu.2021.794075","article-title":"Disease-modifying drug uptake and health service use in the ageing MS population","volume":"12","author":"Ng","year":"2022","journal-title":"Front Immunol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1136\/jnnp-2018-318228","article-title":"Effects of multiple sclerosis disease-modifying therapies on employment measures using patient-reported data","volume":"89","author":"Chen","year":"2018","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s12883-023-03109-6","article-title":"Predictors of severity and outcome of multiple sclerosis relapses","volume":"23","author":"Hosny","year":"2023","journal-title":"BMC Neurol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/j.cct.2011.05.006","article-title":"Are propensity scores really superior to standard multivariable analysis?","volume":"32","author":"Biondi-Zoccai","year":"2011","journal-title":"Contemp Clin Trials"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.jacc.2016.10.060","article-title":"Comparison of propensity score methods and covariate adjustment: evaluation in 4 cardiovascular studies","volume":"69","author":"Elze","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"ref27","volume-title":"Traditional versus early aggressive therapy for multiple sclerosis trial.","year":"2023"},{"key":"ref28","volume-title":"Determining the effectiveness of early intensive versus escalation approaches for RRMS.","year":"2023"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1243589\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T16:04:03Z","timestamp":1694016243000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1243589\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,6]]},"references-count":28,"alternative-id":["10.3389\/fneur.2023.1243589"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2023.1243589","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,6]]},"article-number":"1243589"}}