Genentech announces information regarding Rituximab and a Rare Opportunistic Infection

Arthritis News > Genentech Announcement

Genentech announces rare opportunistic infection in two Lupus patients treated with Rituximab.

John Giles, M.D.

Genentech/Biogen Idec, the manufacturers of rituximab (Rituxan), have reported the occurrence of two cases of progressive multifocal leukoencephalopathy (PML), a rare opportunistic infection of the central nervous system (CNS), in two patients receiving the drug for treatment of major complications of systemic lupus erythematosus (SLE).

About PML:

PML is caused by the JC polyomavirus. JC virus is ubiquitous, carried by most adults and universally harmless except in the setting of extreme immunosuppression, such as that seen in advanced AIDS and bone marrow ransplantation. Neurologic deficits result from demyelization of CNS neurons. The extraordinarily high morbidity and mortality of this rare disorder make it one of the most feared complications of extreme immunosuppression. PML is rare outside of AIDS and iatrogenic immunosuppression, but is sporadically seen in frail elderly patients. Diagnosis is typically made with MRI, cerebrospinal fluid evidence of JC virus, or brain biopsy.

About the two cases:

According to a safety update provided by the manufacturer, both affected SLE patients were receiving rituximab for the treatment of severe hematologic manifestations of SLE. Both were on chronic corticosteroid therapy and had both received azathioprine and cyclophosphamide in the past. Both had received multiple courses of rituximab. Both patients died within months of their diagnosis of PML.

About PML and rituximab:

PML has previously been reported in 23 patients with hematologic malignancies after receiving rituximab, almost all in combination with chemotherapy and/or stem cell transplantation. No cases have been reported in patients receiving rituximab for the treatment of rheumatoid arthritis. Rituximab is not FDA approved for the treatment of SLE, but anecdotal success has been reported for the off-label treatment of SLE-associated hemolytic
anemia and autoimmune cytopenias.

About PML and rheumatic disease:

PML has been reported in patients with RA, SLE, and other rheumatic disorders, invariably attributed to generalized immunosuppression. It has not been independently linked to any currently used biologic agent.

Editorial Comment:

The possibility of a signal for PML with the use of rituximab is important given the extreme severity of the disorder. However, it would seem that the effect seen in the SLE patients reported here is likely the results of extreme immunosuppression and not necessarily attributable to rituximab itself. It is important for practitioners to consider PML in immunosuppressed patients who develop new neurologic symptoms. In addition, care should be given when considering rituximab therapy in patients already aggressively immunosuppressed (i.e. with low CD4 counts), and in those with a history of high grade immunosuppression (such as with cyclophosphamide).