{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:14:39Z","timestamp":1791897279135,"version":"4.3.4"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2019,10,21]],"date-time":"2019-10-21T00:00:00Z","timestamp":1571616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Monoclonal antibodies (MAbs) directed against the CD20 and CD52 antigens are used increasingly in patients with multiple sclerosis (MS). Several life-threatening opportunistic infections have been reported in postmarketing case series. The aim of this study was to investigate the incidence of infections and associated prognostic factors during the first year of treatment in patients receiving anti-CD20 (ocrelizumab or rituximab) or anti-CD52 MAbs (alemtuzumab).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A retrospective study was conducted in patients with MS referring to the Neurodegenerative Diseases Center at the University of Naples Federico II who received MAbs between November 2015 and June 2018.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 163 patients were enrolled. Approximately 40% of patients experienced lymphocytopenia during treatment. Eighty-six infective events were reported in 67 patients (41%). Bacterial infections were significantly more frequent with anti-CD20, whereas viral infections prevailed with alemtuzumab. Cytomegalovirus reactivation rates were significantly higher in the alemtuzumab group than in patients on anti-CD20 (51% vs 6%, P &lt; .001). The overall annualized infection rate was 1.1 per patient-year, higher in patients on anti-CD52 versus those on anti-CD20 regimens (1.5 vs 0.8 per patient-year). Alemtuzumab treatment, prior exposure to \u22652 MS drugs, and iatrogenic immune impairment significantly and independently predicted an infection event (adjusted hazard ratio [aHR], 2.7; P = .013; aHR, 1.7; P = .052; and aHR, 2.9; P = .004; respectively).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Given their considerable infection risk, MS patients receiving MAbs should undergo timely follow up and tailored preventive interventions. Anti-CD52\u2013based treatment, prior exposure to MS drugs, and on-treatment immune impairment are significant predictive factors of infection and their evaluation could help clinicians to stratify a patient\u2019s risk of infection.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ofid\/ofz445","type":"journal-article","created":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T15:16:08Z","timestamp":1573139768000},"source":"Crossref","is-referenced-by-count":31,"title":["Incidence and Predictive Risk Factors of Infective Events in Patients With Multiple Sclerosis Treated With Agents Targeting CD20 and CD52 Surface Antigens"],"prefix":"10.1093","volume":"6","author":[{"given":"Emanuela","family":"Zappulo","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Riccardo","family":"Buonomo","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Sacc\u00e0","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia Valeria","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Scotto","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Scalia","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Cytometry Unit, CEINGE-Biotecnologie Avanzate, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agostino","family":"Nozzolillo","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Lanzillo","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Tosone","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Gentile","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,10,21]]},"reference":[{"key":"2019110802282817800_CIT0001","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s11910-017-0800-8","article-title":"Infections in patients receiving multiple sclerosis disease-modifying therapies","volume":"17","author":"Grebenciucova","year":"2017","journal-title":"Curr Neurol Neurosci Rep"},{"key":"2019110802282817800_CIT0002","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/ane.12835","article-title":"Infections in patients with multiple sclerosis: implications for disease-modifying therapy","volume":"136","author":"Celius","year":"2017","journal-title":"Acta Neurol Scand"},{"key":"2019110802282817800_CIT0003","doi-asserted-by":"crossref","first-page":"ofy174","DOI":"10.1093\/ofid\/ofy174","article-title":"Infectious complications of multiple sclerosis therapies: implications for screening, prophylaxis, and management","volume":"5","author":"Epstein","year":"2018","journal-title":"Open Forum Infect Dis"},{"key":"2019110802282817800_CIT0004","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1080\/14740338.2018.1483330","article-title":"Risk of opportunistic infections in patients treated with alemtuzumab for multiple sclerosis","volume":"17","author":"Buonomo","year":"2018","journal-title":"Expert Opin Drug Saf"},{"key":"2019110802282817800_CIT0005"},{"key":"2019110802282817800_CIT0006","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1016\/S0140-6736(12)61768-1","article-title":"Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial","volume":"380","author":"Coles","year":"2012","journal-title":"Lancet"},{"key":"2019110802282817800_CIT0007","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1056\/NEJMoa1606468","article-title":"Ocrelizumab versus placebo in primary progressive multiple sclerosis","volume":"376","author":"Montalban","year":"2017","journal-title":"N Engl J Med"},{"key":"2019110802282817800_CIT0008","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1002\/ana.21867","article-title":"Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial","volume":"66","author":"Hawker","year":"2009","journal-title":"Ann Neurol"},{"key":"2019110802282817800_CIT0009","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s12883-017-0848-8","article-title":"Listeria monocytogenes infection associated with alemtuzumab - - a case for better preventive strategies","volume":"17","author":"Holm\u00f8y","year":"2017","journal-title":"BMC Neurol"},{"key":"2019110802282817800_CIT0010","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.msard.2018.09.031","article-title":"Bacterial and CMV pneumonia in a patient treated with alemtuzumab for multiple sclerosis","volume":"27","author":"Buonomo","year":"2019","journal-title":"Mult Scler Relat Disord"},{"key":"2019110802282817800_CIT0011","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1177\/1352458516688350","article-title":"Active CMV infection in two patients with multiple sclerosis treated with alemtuzumab","volume":"23","author":"Clerico","year":"2017","journal-title":"Mult Scler"},{"key":"2019110802282817800_CIT0012","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1212\/WNL.0000000000006801","article-title":"Simultaneous CMV and Listeria infection following alemtuzumab treatment for multiple sclerosis","volume":"92","author":"Pappolla","year":"2019","journal-title":"Neurology"},{"key":"2019110802282817800_CIT0013","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1001\/jamaneurol.2016.0146","article-title":"Fulminant central nervous system nocardiosis in a patient treated with alemtuzumab for relapsing-remitting multiple sclerosis","volume":"73","author":"Penkert","year":"2016","journal-title":"JAMA Neurol"},{"key":"2019110802282817800_CIT0014","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.msard.2017.12.005","article-title":"Severe neutropenia after rituximab-treatment of multiple sclerosis","volume":"20","author":"Rissanen","year":"2018","journal-title":"Mult Scler Relat Disord"},{"key":"2019110802282817800_CIT0015","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"2019110802282817800_CIT0016","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1086\/599376","article-title":"Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America","volume":"49","author":"Mermel","year":"2009","journal-title":"Clin Infect Dis"},{"key":"2019110802282817800_CIT0017","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1093\/eurheartj\/ehv319","article-title":"2015 ESC Guidelines for the management of infective endocarditis: the Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM)","volume":"36","author":"Habib","year":"2015","journal-title":"Eur Heart J"},{"key":"2019110802282817800_CIT0018","volume-title":"Treatment of tuberculosis: guidelines","author":"World Health Organization","year":"2009"},{"key":"2019110802282817800_CIT0019","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1086\/588660","article-title":"Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer\/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC\/MSG) Consensus Group","volume":"46","author":"De Pauw","year":"2008","journal-title":"Clin Infect Dis"},{"key":"2019110802282817800_CIT0020","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.jhep.2017.03.021","article-title":"Clinical practice guidelines on the management of hepatitis B virus infection","volume":"67","author":"European Association for the Study of the Liver","year":"2017","journal-title":"J Hepatol"},{"key":"2019110802282817800_CIT0021","article-title":"EASL recommendations on treatment of hepatitis C 2018","author":"Pawlotsky","journal-title":"J Hepatol"},{"key":"2019110802282817800_CIT0022","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1212\/WNL.0b013e31828c2fa1","article-title":"PML diagnostic criteria: consensus statement from the AAN neuroinfectious disease section","volume":"80","author":"Berger","year":"2013","journal-title":"Neurology"},{"key":"2019110802282817800_CIT0023","first-page":"1248","article-title":"Cytomegalovirus reactivation during alemtuzumab therapy for chronic lymphocytic leukemia: incidence and treatment with oral ganciclovir","volume":"89","author":"Laurenti","year":"2004","journal-title":"Haematologica"},{"key":"2019110802282817800_CIT0024","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1586\/ehm.10.77","article-title":"Incidence of cytomegalovirus infection and disease in patients with lymphoproliferative disorders treated with alemtuzumab","volume":"4","author":"Vallejo","year":"2011","journal-title":"Expert Rev Hematol"},{"key":"2019110802282817800_CIT0025","article-title":"Primary cytomegalovirus infection in a patient with relapsing-remitting multiple sclerosis under treatment with alemtuzumab","author":"Eichau","year":"2018; 10.1016\/..2018.03.015","journal-title":"Neurologia (Barcelona, Spain)"},{"key":"2019110802282817800_CIT0026","first-page":"461","article-title":"Infectious complications of a rituximab-based immunosuppressive regimen in patients with glomerular disease","volume":"10","author":"Trivin","year":"2017","journal-title":"Clin Kidney J"}],"container-title":["Open Forum Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ofid\/article-pdf\/6\/11\/ofz445\/30488260\/ofz445.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ofid\/article-pdf\/6\/11\/ofz445\/30488260\/ofz445.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,11,8]],"date-time":"2019-11-08T10:36:03Z","timestamp":1573209363000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ofid\/article\/doi\/10.1093\/ofid\/ofz445\/5601298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,21]]},"references-count":26,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,11,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ofid\/ofz445","relation":{},"ISSN":["2328-8957"],"issn-type":[{"value":"2328-8957","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,11]]},"published":{"date-parts":[[2019,10,21]]},"article-number":"ofz445"}}