{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:00:42Z","timestamp":1791234042039,"version":"4.1.0"},"reference-count":33,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arch Neurol"],"published-print":{"date-parts":[[2011,9,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To describe the development of progressive multifocal leukoencephalopathy (PML) in patients with rheumatoid arthritis (RA) treated with rituximab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Case study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Clinical care for patients with rheumatologic diseases. Most were referred to academic centers for care after diagnosis (Washington University, St Louis, Missouri; Karolinska Insitute, Stockholm, Sweden; and Royal Melbourne Hospital, Melbourne, Australia) while one was cared for in a neurology practice in Dallas, Texas, with consultation by an academic neurovirologist from the University of Colorado in Denver.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients<\/jats:title>\n                    <jats:p>Four patients developing PML in the setting of rituximab therapy for RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Intervention<\/jats:title>\n                    <jats:p>Rituximab therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcome Measures<\/jats:title>\n                    <jats:p>Clinical and pathological observations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Four patients from an estimated population of 129\u00a0000 exposed to rituximab therapy for RA are reported in whom PML developed after administration of this drug. All were women older than 50 years, commonly with Sj\u00f6gren syndrome and a history of treatment for joint disease ranging from 3 to 14 years. One case had no prior biologic and minimal immunosuppressive therapy. Progressive multifocal leukoencephalopathy presented as a progressive neurological disorder, with diagnosis confirmed by detection of JC virus DNA in the cerebrospinal fluid or brain biopsy specimen. Two patients died in less than 1 year from PML diagnosis, while 2 remain alive after treatment withdrawal. Magnetic resonance scans and tissue evaluation confirmed the frequent development of inflammatory PML during the course of the disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These cases suggest an increased risk, about 1 case per 25\u00a0000 individuals, of PML in patients with RA being treated with rituximab. Inflammatory PML may occur in this setting even while CD20 counts remain low.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/archneurol.2011.103","type":"journal-article","created":{"date-parts":[[2011,5,10]],"date-time":"2011-05-10T02:19:39Z","timestamp":1304993979000},"page":"1156","source":"Crossref","is-referenced-by-count":238,"title":["Rituximab-Associated Progressive Multifocal Leukoencephalopathy in Rheumatoid Arthritis"],"prefix":"10.1001","volume":"68","author":[{"given":"David B.","family":"Clifford","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beau","family":"Ances","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Costello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shari","family":"Rosen-Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Andersson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Parks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arie","family":"Perry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju","family":"Yerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Alvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth L.","family":"Tyler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"4","key":"ref-noc15023-1","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/S1474-4422(10)70040-5","article-title":"Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis.","volume":"9","author":"Tan","year":"2010","journal-title":"Lancet Neurol"},{"issue":"2","key":"ref-noc15023-2","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1002\/ana.v60:2","article-title":"Progressive multifocal leukoencephalopathy revisited: has the disease outgrown its name?","volume":"60","author":"Koralnik","year":"2006","journal-title":"Ann Neurol"},{"issue":"3","key":"ref-noc15023-3","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1002\/ana.22128","article-title":"Anti-JC virus antibodies: implications for PML risk stratification.","volume":"68","author":"Gorelik","year":"2010","journal-title":"Ann Neurol"},{"issue":"3","key":"ref-noc15023-4","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1002\/ana.22107","article-title":"Assessment of JC virus DNA in blood and urine from natalizumab-treated patients.","volume":"68","author":"Rudick","year":"2010","journal-title":"Ann Neurol"},{"issue":"1","key":"ref-noc15023-5","doi-asserted-by":"publisher","first-page":"59","DOI":"10.3109\/13550289809113482","article-title":"Progressive multifocal leukoencephalopathy in patients with HIV infection.","volume":"4","author":"Berger","year":"1998","journal-title":"J Neurovirol"},{"issue":"1","key":"ref-noc15023-6","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1128\/CMR.5.1.49","article-title":"Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain.","volume":"5","author":"Major","year":"1992","journal-title":"Clin Microbiol Rev"},{"issue":"4","key":"ref-noc15023-7","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1056\/NEJMoa051782","article-title":"Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis.","volume":"353","author":"Kleinschmidt-DeMasters","year":"2005","journal-title":"N Engl J Med"},{"issue":"4","key":"ref-noc15023-8","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1056\/NEJMoa051847","article-title":"Progressive multifocal leukoencephalopathy in a patient treated with natalizumab.","volume":"353","author":"Langer-Gould","year":"2005","journal-title":"N Engl J Med"},{"issue":"4","key":"ref-noc15023-9","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1056\/NEJMoa051586","article-title":"Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's disease.","volume":"353","author":"Van Assche","year":"2005","journal-title":"N Engl J Med"},{"issue":"9","key":"ref-noc15023-10","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1056\/NEJMoa054693","article-title":"Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy.","volume":"354","author":"Yousry","year":"2006","journal-title":"N Engl J Med"},{"issue":"4","key":"ref-noc15023-11","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1016\/S1474-4422(10)70028-4","article-title":"Natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: lessons from 28 cases [published correction appears in Lancet Neurol. 2010;9(5):463].","volume":"9","author":"Clifford","year":"2010","journal-title":"Lancet Neurol"},{"issue":"8","key":"ref-noc15023-12","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1016\/S1470-2045(09)70161-5","article-title":"Monoclonal antibody-associated progressive multifocal leucoencephalopathy in patients treated with rituximab, natalizumab, and efalizumab: a review from the Research on Adverse Drug Events and Reports (RADAR) Project.","volume":"10","author":"Carson","year":"2009","journal-title":"Lancet Oncol"},{"issue":"3","key":"ref-noc15023-13","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1080\/10428190902779257","article-title":"Rituximab and progressive multi-focal leukoencephalopathy: the jury is deliberating.","volume":"50","author":"Carson","year":"2009","journal-title":"Leuk Lymphoma"},{"issue":"20","key":"ref-noc15023-14","doi-asserted-by":"publisher","first-page":"4834","DOI":"10.1182\/blood-2008-10-186999","article-title":"Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project.","volume":"113","author":"Carson","year":"2009","journal-title":"Blood"},{"key":"ref-noc15023-15","doi-asserted-by":"publisher","first-page":"iii64","DOI":"10.1136\/ard.2008.097972","article-title":"Progressive multifocal leucoencephalopathy in the rheumatic diseases: assessing the risks of biological immunosuppressive therapies.","volume":"67","author":"Calabrese","year":"2008","journal-title":"Ann Rheum Dis"},{"issue":"2","key":"ref-noc15023-16","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.autrev.2008.07.006","article-title":"Progressive multifocal leukoencephalopathy in patients with rheumatic diseases: are patients with systemic lupus erythematosus at particular risk?","volume":"8","author":"Molloy","year":"2008","journal-title":"Autoimmun Rev"},{"issue":"12","key":"ref-noc15023-17","doi-asserted-by":"publisher","first-page":"3761","DOI":"10.1002\/art.v60:12","article-title":"Progressive multifocal leukoencephalopathy: a national estimate of frequency in systemic lupus erythematosus and other rheumatic diseases.","volume":"60","author":"Molloy","year":"2009","journal-title":"Arthritis Rheum"},{"issue":"11","key":"ref-noc15023-18","doi-asserted-by":"publisher","first-page":"3225","DOI":"10.1002\/art.v60:11","article-title":"Progressive multifocal leukoencephalopathy following rituximab treatment in a patient with rheumatoid arthritis.","volume":"60","author":"Fleischmann","year":"2009","journal-title":"Arthritis Rheum"},{"issue":"7","key":"ref-noc15023-19","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1007\/s11547-006-0095-3","article-title":"Conventional and diffusion-weighted MRI in progressive multifocal leukoencephalopathy: new elements for identification and follow-up.","volume":"111","author":"da Pozzo","year":"2006","journal-title":"Radiol Med"},{"issue":"10","key":"ref-noc15023-20","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1007\/s00234-003-0966-4","article-title":"Progressive multifocal leukoencephalopathy: analysis of lesion development with diffusion-weighted MRI.","volume":"45","author":"Mader","year":"2003","journal-title":"Neuroradiology"},{"issue":"1","key":"ref-noc15023-21","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1086\/313598","article-title":"Highly active antiretroviral therapy and progressive multifocal leukoencephalopathy: effects on cerebrospinal fluid markers of JC virus replication and immune response.","volume":"30","author":"Giudici","year":"2000","journal-title":"Clin Infect Dis"},{"issue":"10","key":"ref-noc15023-22","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1016\/S1473-3099(09)70226-9","article-title":"Progressive multifocal leukoencephalopathy in HIV-1 infection.","volume":"9","author":"Cinque","year":"2009","journal-title":"Lancet Infect Dis"},{"issue":"15","key":"ref-noc15023-23","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1212\/WNL.0b013e3181f73600","article-title":"Incidence of progressive multifocal leukoencephalopathy in patients without HIV.","volume":"75","author":"Amend","year":"2010","journal-title":"Neurology"},{"issue":"8","key":"ref-noc15023-24","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1001\/archdermatol.2009.175","article-title":"Progressive multifocal leukoencephalopathy, efalizumab, and immunosuppression: a cautionary tale for dermatologists.","volume":"145","author":"Korman","year":"2009","journal-title":"Arch Dermatol"},{"issue":"3","key":"ref-noc15023-25","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1002\/ana.22137","article-title":"JC virus persistence following progressive multifocal leukoencephalopathy in multiple sclerosis patients treated with natalizumab.","volume":"68","author":"Ryschkewitsch","year":"2010","journal-title":"Ann Neurol"},{"issue":"7","key":"ref-noc15023-26","doi-asserted-by":"publisher","first-page":"3361","DOI":"10.1128\/JVI.01809-06","article-title":"Frequency and phenotype of JC virus-specific CD8+ T lymphocytes in the peripheral blood of patients with progressive multifocal leukoencephalopathy.","volume":"81","author":"Lima","year":"2007","journal-title":"J Virol"},{"issue":"3","key":"ref-noc15023-27","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1002\/ana.22185","article-title":"Progressive multifocal leukoencephalopathy: can we reduce risk in patients receiving biological immunomodulatory therapies?","volume":"68","author":"Tyler","year":"2010","journal-title":"Ann Neurol"},{"issue":"19","key":"ref-noc15023-28","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1056\/NEJM199805073381903","article-title":"Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection: AIDS Clinical Trials Group 243 Team.","volume":"338","author":"Hall","year":"1998","journal-title":"N Engl J Med"},{"issue":"14","key":"ref-noc15023-29","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1097\/QAD.0b013e32830a5043","article-title":"Cidofovir in addition to antiretroviral treatment is not effective for AIDS-associated progressive multifocal leukoencephalopathy: a multicohort analysis.","volume":"22","author":"De Luca","year":"2008","journal-title":"AIDS"},{"issue":"9","key":"ref-noc15023-30","first-page":"A28","article-title":"Mefloquine treatment in patients with progressive multifocal leukoencephalopathy.","volume":"76","author":"Clifford","year":"2011","journal-title":"Neurology"},{"issue":"19","key":"ref-noc15023-31","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1212\/WNL.0b013e3181c0d4a1","article-title":"Determinants of survival in progressive multifocal leukoencephalopathy.","volume":"73","author":"Marzocchetti","year":"2009","journal-title":"Neurology"},{"issue":"5","key":"ref-noc15023-32","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1212\/01.wnl.0000341766.59028.9d","article-title":"Effect of plasma exchange in accelerating natalizumab clearance and restoring leukocyte function.","volume":"72","author":"Khatri","year":"2009","journal-title":"Neurology"},{"issue":"17","key":"ref-noc15023-33","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.1212\/01.wnl.0000343510.08643.74","article-title":"PML-IRIS in patients with HIV infection: clinical manifestations and treatment with steroids.","volume":"72","author":"Tan","year":"2009","journal-title":"Neurology"}],"container-title":["Archives of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/articlepdf\/1108037\/noc15023_1156_1164_1678139625.99306.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T17:30:28Z","timestamp":1678123828000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/fullarticle\/1108037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,9,1]]},"references-count":33,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2011,9,1]]}},"URL":"https:\/\/doi.org\/10.1001\/archneurol.2011.103","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.13328006.14691127","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.13328006.793492816","asserted-by":"object"}]},"ISSN":["0003-9942"],"issn-type":[{"value":"0003-9942","type":"print"}],"subject":[],"published":{"date-parts":[[2011,9,1]]}}}