{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:38:44Z","timestamp":1774312724036,"version":"3.50.1"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T00:00:00Z","timestamp":1734048000000},"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<\/jats:title><jats:p>The potential link between disease-modifying therapies (DMTs) and malignancy in multiple sclerosis (MS) patients has generated significant concern, particularly given the immunosuppressive nature of these treatments. Conflicting evidence in the literature has left this issue unresolved, underscoring the need for definitive research to inform clinical practice. This study addresses this gap by examining cancer occurrence among MS patients on DMTs treated at two tertiary-care centers in Saudi Arabia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To report and analyze cases of malignancy in MS patients treated with DMTs and identify associated risk factors, including demographic characteristics, Expanded Disability Status Scale (EDSS) scores, treatment duration, and cumulative DMT exposure. The study also seeks to contribute to the development of evidence-based cancer screening protocols for MS patients at elevated risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective review was performed on medical records of MS patients treated with DMTs at two tertiary-care centers in Saudi Arabia from June 2015 to December 2023. The study included 860 patients, with data collected on demographics, MS subtype, DMT usage, and subsequent cancer diagnoses. A comprehensive literature review, covering publications from February 1976 to May 2024, supplemented the review to contextualize findings within the broader research landscape.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 860 MS patients on DMTs, 10 (1.16%) developed malignancies, predominantly female (80%), with an average age of 50.9\u202fyears. The majority had relapsing\u2013remitting MS (RRMS) (90%), with interferon beta (70%) and ocrelizumab (60%) being the most frequently used DMTs. The median duration of DMT exposure prior to cancer diagnosis was 52\u202fmonths. The observed malignancies included gynecological cancers, breast cancer, thyroid cancer, and nasopharyngeal carcinoma, with 60% diagnosed at advanced stages (III-IV).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This case series highlights instances of malignancy among MS patients undergoing DMTs, suggesting a potential link that warrants further investigation. The findings underscore the need for vigilant cancer screening and patient education as integral components of MS management. The literature review reinforces the necessity for ongoing research to better understand the risks associated with DMTs, aiding in the development of more informed clinical guidelines. Further large-scale, longitudinal studies are crucial to elucidate the causality and guide safer treatment strategies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2024.1492678","type":"journal-article","created":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T05:10:51Z","timestamp":1734066651000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Risk of malignancy and the use of disease-modifying therapy in multiple sclerosis: exploring the role of DMT in a multi-center study"],"prefix":"10.3389","volume":"15","author":[{"given":"Mohammed","family":"Bayounis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Bin Mahfooz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Assiri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yousef","family":"Alghamdi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fahad","family":"Alturki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahdi","family":"Almutairi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdullah","family":"Alshelawy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Alosaimi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faisal","family":"Almutawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdulrahman","family":"Alammar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yahya","family":"Alyahya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osama","family":"Khojah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seraj","family":"Makkawi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaser","family":"Al Malik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1016\/S0140-6736(08)61620-7","article-title":"Multiple sclerosis","volume":"372","author":"Compston","year":"2008","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"11718","DOI":"10.3390\/ijms130911718","article-title":"Environmental risk factors for multiple sclerosis: a review with a focus on molecular mechanisms","volume":"13","author":"O\u2019Gorman","year":"2012","journal-title":"Int J Mol Sci"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1001\/jama.2020.26858","article-title":"Diagnosis and treatment of multiple sclerosis","volume":"325","author":"McGinley","year":"2021","journal-title":"JAMA"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet Neurol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1093\/brain\/aww258","article-title":"Progressive multiple sclerosis: from pathogenic mechanisms to treatment","volume":"140","author":"Correale","year":"2017","journal-title":"Brain"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"78","DOI":"10.3390\/brainsci7070078","article-title":"Multiple sclerosis: immunopathology and treatment update","volume":"7","author":"Dargahi","year":"2017","journal-title":"Brain Sci"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1007\/s40263-015-0261-z","article-title":"Sphingosine 1-phosphate receptor modulators in multiple sclerosis","volume":"29","author":"Subei","year":"2015","journal-title":"CNS Drugs"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1016\/S0140-6736(21)00244-0","article-title":"Sphingosine 1-phosphate receptor modulators in multiple sclerosis and other conditions","volume":"398","author":"McGinley","year":"2021","journal-title":"Lancet"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1007\/s40263-020-00704-w","article-title":"Anti-CD20 monoclonal antibodies for relapsing and progressive multiple sclerosis","volume":"34","author":"Sellebjerg","year":"2020","journal-title":"CNS Drugs"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"20552173211065731","DOI":"10.1177\/20552173211065731","article-title":"Infectious risk in multiple sclerosis patients treated with disease- modifying therapies: a three-year observational cohort study","volume":"8","author":"Zingaropoli","year":"2022","journal-title":"Mult Scler J Exp Transl Clin"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1007\/s40263-018-0564-y","article-title":"Cancer risk in patients with multiple sclerosis: potential impact of disease-modifying drugs","volume":"32","author":"Lebrun","year":"2018","journal-title":"CNS Drugs"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1177\/1352458514564489","article-title":"A systematic review of the incidence and prevalence of cancer in multiple sclerosis","volume":"21","author":"Marrie","year":"2015","journal-title":"Mult Scler"},{"key":"ref13","unstructured":"2020"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1002\/ana.25701","article-title":"Cancer risk for fingolimod, natalizumab, and rituximab in multiple sclerosis patients","volume":"87","author":"Alping","year":"2020","journal-title":"Ann Neurol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1136\/jnnp-2013-307238","article-title":"Assessment of cancer risk with \u03b2-interferon treatment for multiple sclerosis","volume":"85","author":"Kingwell","year":"2014","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"102747","DOI":"10.1016\/j.msard.2021.102747","article-title":"Cancer diagnosis in a Spanish cohort of multiple sclerosis patients under dimethylfumarate treatment","volume":"49","author":"G\u00f3mez-Moreno","year":"2021","journal-title":"Mult Scler Relat Disord"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1186\/s12883-017-0932-0","article-title":"Association between multiple sclerosis, cancer risk, and immunosuppressant treatment: a cohort study","volume":"17","author":"Ragonese","year":"2017","journal-title":"BMC Neurol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.msard.2018.12.014","article-title":"Multiple sclerosis and cancer incidence: a Danish nationwide cohort study","volume":"28","author":"N\u00f8rgaard","year":"2019","journal-title":"Mult Scler Relat Disord"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"103679","DOI":"10.1016\/j.msard.2022.103679","article-title":"Incidence of malignant neoplasms and mortality in people affected by multiple sclerosis in the epoch of disease-modifying treatments: a population-based study on Tuscan residents","volume":"60","author":"Mariottini","year":"2022","journal-title":"Mult Scler Relat Disord"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1007\/s10549-004-2229-4","article-title":"Cancer incidence in multiple sclerosis and effects of immunomodulatory treatments","volume":"89","author":"Achiron","year":"2005","journal-title":"Breast Cancer Res Treat"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"337","DOI":"10.3389\/fneur.2019.00337","article-title":"Cancer risk and multiple sclerosis: evidence from a large Italian cohort","volume":"10","author":"D\u2019Amico","year":"2019","journal-title":"Front Neurol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1007\/s00415-011-5929-9","article-title":"Cancer and multiple sclerosis in the era of disease-modifying treatments","volume":"258","author":"Lebrun","year":"2011","journal-title":"J Neurol"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2024.1492678\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T05:10:55Z","timestamp":1734066655000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2024.1492678\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,13]]},"references-count":22,"alternative-id":["10.3389\/fneur.2024.1492678"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2024.1492678","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,13]]},"article-number":"1492678"}}