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FDA Alert Regarding Lupus Medication: an HSS Rheumatology Perspective

Progressive Multifocal Leukoencephalopathy (PML) in Patients Treated with Mycophenolate mofetil (CellCept)


Michael D. Lockshin, MD

Attending Rheumatologist, Hospital for Special Surgery
Professor of Medicine, Weill Cornell Medical College
Director, Barbara Volcker Center for Women and Rheumatic Disease

Allan Gibofsky, MD

Attending Physician, Hospital for Special Surgery
Professor of Medicine and Public Health, Weill Cornell Medical College

Joseph A. Markenson, MD

Attending Physician, Hospital for Special Surgery
Professor of Clinical Medicine, Weill Cornell Medical College
Attending Physician, Department of Medicine, Memorial Sloan-Kettering Cancer Center

Theodore R. Fields, MD, FACP

Attending Physician, Hospital for Special Surgery
Professor of Clinical Medicine, Weill Cornell Medical College

Stephen A. Paget, MD, FACP, FACR

Physician-in-Chief Emeritus, Hospital for Special Surgery

On April 10, 2008, the FDA released a safety alert concerning a possible relationship between CellCept (mycophenolate mofetil) and a devastating neurological disease known as progressive multifocal leukoencephalopathy (PML). [1]

This adds to the wide list of associations between PML and immune deficiency of any cause.  PML occurs in patients born with immune deficiency, AIDS patients, patients with sarcoidosis, and patients undergoing immunosuppressive treatment for rheumatic diseases (in particular systemic lupus erythematosus) as well as Crohn's disease and multiple sclerosis.  Lupus patients were previously warned about the occurrence of PML after treatment with rituximab.  Recent medical reviews noted the association of PML and rituximab treatment in rheumatic disease patients and concluded that such complications were extremely rare. [2, 3]

PML occurred in lupus patients long before rituximab and CellCept were used as treatments for lupus.  There is little reason to believe either that lupus patients are uniquely susceptible or that these two drugs are uniquely dangerous in causing PML. Rather, PML is a well recognized complication of intense immunosuppression and is among the many infectious complications to which persons undergoing such treatment are at risk.  Recent reports of PML stand as a warning to physicians not to overtreat their lupus patients, but PML is sufficiently rare that intense immunosuppression remains the best option for patients who have life-threatening disease.


1. FDA Safety Alert, April 10, 2008 

2. Looney RJ, Srinivasan R, Calabrese LH. The effects of rituximab on immunocompetency in patients with autoimmune disease. Arthritis Rheum. 2008 Jan;58(1):5-14.

3. Calabrese LH, Molloy ES, Huang D, et al. progressive multifocal leukoencephalopathy in rheumatic diseases: evolving clinical and pathologic patterns of disease.  Arthritis Rheum 2007; 56: 2116-2128

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