Rituxan (rituximab) and progressive multifocal leukoencephalopathy (PML)
admin September 12th, 2008
The FDA have posted details of a warning by the manufacturer of rituximab concerning a case report of progressive multifocal leukoencephalopathy:
Genentech informed healthcare professionals of revisions to prescribing information for Rituxan regarding a case of progressive multifocal leukoencephalopathy (PML) leading to death in a patient with rheumatoid arthritis who received Rituxan in a long-term safety extension clinical study. The patient developed a JC virus infection with resultant PML and death 18 months after taking the last dose of Rituxan. Healthcare professionals treating patients with Rituxan should consider PML in any patient presenting with new onset neurologic manifestations. Additionally, consultation with a neurologist, brain MRI and lumbar puncture should be considered as clinically indicated.
The manufacturer’s letter [PDF] provides further details of the case:
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 of Rituxan. 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 Sjogren’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.
The Rituxan package insert WARNING section on PML has previously noted reports of PML in patients with hematologic malignancies and autoimmune diseases for which Rituxan is not approved. It has been updated to reflect the case of PML in an RA patient treated with Rituxan and is enclosed [PDF] for your reference [See WARNINGS and PRECAUTIONS: 5.4 Progressive Multifocal Leukoencephalopathy (PML)].