Rituximab-associated progressive multifocal leukoencephalopathy in rheumatoid arthritis

David B. Clifford, Beau Ances, Craig Costello, Shari Rosen-Schmidt, Magnus Andersson, Deborah Parks, Arie Perry, Raju Yerra, Robert Schmidt, Enrique Alvarez, Kenneth L. Tyler

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197 Scopus citations

Abstract

Objective: To describe the development of progressive multifocal leukoencephalopathy (PML) in patients with rheumatoid arthritis (RA) treated with rituximab. Design: Case study. Setting: 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. Patients: Four patients developing PML in the setting of rituximab therapy for RA. Intervention: Rituximab therapy. Main Outcome Measures: Clinical and pathological observations. Results: Four patients from an estimated population of 129 000 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 Sjögren 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. Conclusion: These cases suggest an increased risk, about 1 case per 25 000 individuals, of PML in patients with RA being treated with rituximab. Inflammatory PMLmay occur in this setting even while CD20 counts remain low.

Original languageEnglish
Pages (from-to)1156-1164
Number of pages9
JournalArchives of neurology
Volume68
Issue number9
DOIs
StatePublished - Sep 2011

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