Patients with rheumatoid arthritis who receive Mabthera (rituximab) may have an increased risk of developing progressive multifocal leukoencephalopathy, according to a safety warning issued by the FDA and the drug’s US manufacturer Genetech.
The warning follows the third case of progressive multifocal leukoencephalopathy (PML) in a patient with rheumatoid arthritis (RA) treated with the TNF blocker.
The patient concerned was a 73-year old female with a three-year history of sero-negative RA, who had received treatment with leflunomide, hydroxychloroquine and prednisone. She developed dysesthesias and ataxia four to six months following one course of Mabthera. PML was diagnosed based on clinical symptoms, MRI findings, and detection of JC viral DNA in the CSF by PCR.
Mabthera has also been associated with fatal infusion reactions, tumor lysis syndrome (TLS) and severe mucocutaneous reactions. Hepatitis B reactivation and cardiac arrhythmias and angina have also been observed.
While the latest PML case is the first to occur in a patient without previous exposure to a TNF antagonist, two fatal cases of confirmed PML have previously been reported in patients with RA treated with Mabthera. These cases involved a 51-year-old woman and a 73-year-old woman with possible risk factors for the development of PML, including oropharyngeal malignancy treated with chemotherapy and radiation therapy, and long-standing lymphopenia prior to and during Mabthera treatment.
Genetech said healthcare professionals are advised to consider PML in any patient being treated with Mabthera who presents with new onset neurological manifestations. Consultation with a neurologist, brain MRI, and lumbar puncture should be considered as clinically indicated.