{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T06:11:21Z","timestamp":1774678281705,"version":"3.50.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T00:00:00Z","timestamp":1737590400000},"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. Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Ofatumumab, a fully human monoclonal antibody targeting CD20, is approved for the treatment of relapsing multiple sclerosis. Comprehensive real-world safety data are crucial for informing clinical practice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The FDA Adverse Event Reporting System database was utilized to perform a disproportionality analysis, covering reports from Q3 2020 to Q2 2024, in which ofatumumab was identified as the primary suspected drug. Statistical approaches used included the Reporting Odds Ratio, Proportional Reporting Ratio, Bayesian Confidence Propagation Neural Network, and Multi-item Gamma Poisson Shrinker. The timing of adverse events was assessed using the Weibull distribution model to highlight temporal risk patterns.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Known adverse reactions, such as injection site reactions and upper respiratory tract infections, displayed positive signals. Additionally, novel off-label adverse events, including brain fog, muscle spasms, and mood alterations, were identified, marking the first real-world evidence of these potential risks. Temporal analysis revealed that most adverse events occurred within the first month of treatment, indicating an early risk phase. Subgroup analysis demonstrated notable differences in adverse event profiles by gender and age, with males more prone to hyperhidrosis and older patients more susceptible to neurological symptoms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This real-world analysis of ofatumumab provides important safety insights, confirming known adverse reactions and identifying additional potential risks. Early and tailored monitoring protocols during the initial treatment phase, including regular neurological and psychiatric assessments, are recommended to optimize patient safety and outcomes. Prospective studies are recommended to validate these results and explore the underlying mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2024.1521726","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T06:58:44Z","timestamp":1737615524000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Real-world pharmacovigilance of ofatumumab in multiple sclerosis: a comprehensive FAERS data analysis"],"prefix":"10.3389","volume":"15","author":[{"given":"Hui","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1517\/14740338.2016.1167184","article-title":"Data mining spontaneous adverse drug event reports for safety signals in singapore \u2013 a comparison of three different disproportionality measures","volume":"15","author":"Ang","year":"2016","journal-title":"Expert Opin. Drug Saf."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1007\/s12325-018-0805-y","article-title":"Interpretation and impact of real-world clinical data for the practicing clinician","volume":"35","author":"Blonde","year":"2018","journal-title":"Adv. Ther."},{"key":"B3","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1111\/j.1600-065X.2008.00661.x","article-title":"Regulatory B cells as inhibitors of immune responses and inflammation","volume":"224","author":"Bouaziz","year":"2008","journal-title":"Immunol. Rev."},{"key":"B4","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1007\/s40265-024-02011-w","article-title":"Drugs targeting CD20 in multiple sclerosis: pharmacology, efficacy, safety, and tolerability","volume":"84","author":"Carlson","year":"2024","journal-title":"Drugs"},{"key":"B5","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/ar3736","article-title":"Interleukin-10 produced by B cells is crucial for the suppression of Th17\/Th1 responses, induction of T regulatory type 1 cells and reduction of collagen-induced arthritis","volume":"14","author":"Carter","year":"2012","journal-title":"Arthritis Res. Ther."},{"key":"B6","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.coph.2020.10.002","article-title":"Targeting B cells for inflammatory bowel disease treatment: back to the future","volume":"55","author":"Castro-Dopico","year":"2020","journal-title":"Curr. Opin. Pharmacol., Endocr. metabolic Dis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1097\/WCO.0000000000000091","article-title":"Migraine and estrogen","volume":"27","author":"Chai","year":"2014","journal-title":"Curr. Opin. Neurol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1007\/s00415-023-12007-3","article-title":"Key characteristics of anti-CD20 monoclonal antibodies and clinical implications for multiple sclerosis treatment","volume":"271","author":"Delgado","year":"2024","journal-title":"J. Neurol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1004795","DOI":"10.3389\/fimmu.2023.1004795","article-title":"Anti-CD20 therapies in multiple sclerosis: from pathology to the clinic","volume":"14","author":"De S\u00e8ze","year":"2023","journal-title":"Front. Immunol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1177\/009286150003400133","article-title":"Establishing a MedDRA safety surveillance unit","volume":"34","author":"Doan","year":"2000","journal-title":"Ther. Innov. Regul. Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1002\/pds.677","article-title":"Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports","volume":"10","author":"Evans","year":"2001","journal-title":"Pharmacoepidem. Dr. S."},{"key":"B12","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/S1474-4422(24)00140-6","article-title":"B cell-targeting chimeric antigen receptor T cells as an emerging therapy in neuroimmunological diseases","volume":"23","author":"Haghikia","year":"2024","journal-title":"Lancet Neurology"},{"key":"B13","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1056\/NEJMoa1917246","article-title":"Ofatumumab versus teriflunomide in multiple sclerosis","volume":"383","author":"Hauser","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1177\/13524585231195346","article-title":"Efficacy and safety of four-year ofatumumab treatment in relapsing multiple sclerosis: the ALITHIOS open-label extension","volume":"29","author":"Hauser","year":"2023","journal-title":"Mult. Scler."},{"key":"B15","doi-asserted-by":"publisher","first-page":"295","DOI":"10.2147\/JMDH.S160029","article-title":"Real world data: an opportunity to supplement existing evidence for the use of long-established medicines in health care decision making","volume":"11","author":"Katkade","year":"2018","journal-title":"J. Multidiscip. Healthc."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1177\/13524585211055934","article-title":"Effect of ofatumumab versus placebo in relapsing multiple sclerosis patients from Japan and Russia: phase 2 APOLITOS study","volume":"28","author":"Kira","year":"2022","journal-title":"Mult. Scler."},{"key":"B17","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1007\/s13311-022-01224-9","article-title":"Monoclonal antibodies in the treatment of relapsing multiple sclerosis: an overview with emphasis on pregnancy, vaccination, and risk management","volume":"19","author":"Krajnc","year":"2022","journal-title":"Neurotherapeutics"},{"key":"B18","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1111\/j.1365-2133.1994.tb05000.x","article-title":"Androgens and sweating","volume":"131","author":"Kunkeler","year":"1994","journal-title":"Br. J. Dermatol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1038\/s41590-018-0135-x","article-title":"Reassessing B cell contributions in multiple sclerosis","volume":"19","author":"Li","year":"2018","journal-title":"Nat. Immunol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1001\/jama.2020.26858","article-title":"Diagnosis and treatment of multiple sclerosis: a review","volume":"325","author":"McGinley","year":"2021","journal-title":"JAMA"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.3390\/cells11081355","article-title":"Role of estrogens in menstrual migraine","volume":"11","author":"Nappi","year":"2022","journal-title":"Cells"},{"key":"B22","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1080\/10543406.2022.2154940","article-title":"Parameter estimation of weibull distribution for the number of days between drug administration and early onset adverse event","volume":"33","author":"Ogura","year":"2022","journal-title":"J. Biopharm. Statistics"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1884","DOI":"10.3389\/fimmu.2020.01884","article-title":"Regulatory B cells and its role in central nervous system inflammatory demyelinating diseases","volume":"11","author":"Ran","year":"2020","journal-title":"Front. Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"3260","DOI":"10.1210\/jc.2009-2546","article-title":"Dissimilar hepatotoxicity profiles of propylthiouracil and methimazole in children","volume":"95","author":"Rivkees","year":"2010","journal-title":"J. Clin. Endocr. Metab."},{"key":"B25","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1002\/pds.1001","article-title":"The reporting odds ratio and its advantages over the proportional reporting ratio","volume":"13","author":"Rothman","year":"2004","journal-title":"Pharmacoepidem. Dr. S."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.88.16_supplement.S24.003","article-title":"Ofatumumab differs from rituximab by effectively targeting lymph node B cells and achieving faster post-treatment repletion (S24.003)","volume":"88","author":"Smith","year":"2017","journal-title":"Neurology"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.3389\/fimmu.2019.01340","article-title":"Imaging mass cytometry and single-cell genomics reveal differential depletion and repletion of B-cell populations following ofatumumab treatment in cynomolgus monkeys","volume":"10","author":"Theil","year":"2019","journal-title":"Front. Immunol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1016\/S0140-6736(18)30481-1","article-title":"Multiple sclerosis","volume":"391","author":"Thompson","year":"2018","journal-title":"Lancet"},{"key":"B29","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1002\/sim.4780100621","article-title":"Random models for margins of a 2 x 2 contingency table and application to pharmacovigilance","volume":"10","author":"Tubert","year":"1991","journal-title":"Stat. Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1007\/s40263-022-00961-x","article-title":"The efficacy and safety of anti-CD20 antibody treatments in relapsing multiple sclerosis: a systematic review and network meta-analysis","volume":"36","author":"Wu","year":"2022","journal-title":"CNS Drugs"},{"key":"B31","doi-asserted-by":"publisher","first-page":"102777","DOI":"10.1016\/j.autrev.2021.102777","article-title":"B lymphocytes, the gastrointestinal tract and autoimmunity","volume":"20","author":"Zouali","year":"2021","journal-title":"Autoimmun. Rev."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1521726\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T06:58:46Z","timestamp":1737615526000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1521726\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,23]]},"references-count":31,"alternative-id":["10.3389\/fphar.2024.1521726"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1521726","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,23]]},"article-number":"1521726"}}