ROCKVILLE, Maryland—The Food and Drug Administration (FDA) MedWatch system issued a warning September 11, 2008, regarding a case of progressive multifocal leukoencephalopathy (PML) leading to death in a patient with rheumatoid arthritis (RA) who received rituximab (Rituxan^®, Genentech-Biogen Idec) in a long-term safety extension clinical study. The Rituxan package insert warning section on PML has been updated to reflect this case.¹

Previous reports of PML had involved off-label use of Rituxan in patients with hematological malignancies and autoimmune disease. Rituxan in combination with methotrexate is approved to reduce signs and symptoms and to slow the progression of structural damage in adults with moderate-to-severe active RA who had had inadequate response to one or more TNF antagonist therapies.

According to a Dear Healthcare Professional from Genentech chief medical officer Hal Barron, MD, and Biogen Idec vice president David Hagerty, MD, this is the first reported case of PML in a Rituxan-treated RA patient.

“The case of JC virus infection with resultant PML and death was reported in an RA patient treated with Rituxan and was diagnosed approximately 18 months after the last dose…. This case was confounded by the patient's development of oropharyngeal cancer, which was treated with chemotherapy (a platinum containing regimen) and radiation therapy 9 months prior to the development of PML. The patient had longstanding RA treated with immunosuppressants and a complex medical and rheumatologic history including Sjögren’s syndrome and undetectable complement C4 levels. Treatment for RA included methotrexate, steroids, and a TNF antagonist prior to Rituxan therapy; and methotrexate and steroids during and after Rituxan therapy,” Drs. Barron and Hagerty said.

Translating warning into practice

According to the FDA, “Healthcare professionals treating patients with Rituxan should consider PML in any patient presenting with new onset neurological manifestations. Additionally, consultation with a neurologist [who will perform] brain MRI and lumbar puncture should be considered as clinically indicated.”

Drs. Barron and Hagerty advise, “In patients who develop PML, Rituxan should be discontinued and reductions or discontinuation in concomitant immunosuppressive therapy and appropriate treatment including antiviral therpay should be considered. There are no known interventions that can reliably prevent PML or adequately treat PML if it occurs.”

Reference

1. FDA resource page. FDA Website. http://www.fda.gov/medwatch/safety/2008/safety08.htm#Rituxan.