Rituxan® Safety Information Q&A
1. What is the latest safety news about Rituxan®?
Genentech and its collaborator, Biogen Idec are working with the U.S. Food and Drug Administration (FDA) to update the Rituxan® (rituximab) prescribing information to include additional safety information in the warnings section of the label related to two reports of progressive multifocal leukoencephalopathy (PML) in two patients treated with the drug, one of whom was from the United States.
2. What is Progressive Multifocal Leukoencephalopathy (PML) and if I am currently taking Rituxan®, what does this news mean to me?
PML is a rare disorder of the nervous system, primarily affecting individuals with suppressed immune systems. PML is caused by the activation of a human polyomavirus, the JC virus, which resides in latent form in up to 80 percent of healthy adults. PML is characterized by demyelination or destruction of the myelin sheath that covers nerve cells. The myelin sheath is the fatty covering that acts as an insulator on nerve fibers in the brain. PML can result in severe disability or death. PML has been diagnosed in more than 25 patients with lupus who were not treated with Rituxan®, but were treated with other immunosuppressing agents like cytoxan and imuran.
Because of the extremely low occurrence of PML in lupus patients receiving Rituxan®, at this time neither the FDA nor Genentech have put or have plans to put the current clinical trials on hold.
Genentech and its collaborator, Biogen Idec are working with the FDA to update the Rituxan® prescribing information to include additional safety information in the warnings section of the label, and are also updating the consent forms related to the current clinical trials to reflect this new information. The existing consent forms already state a potential risk for PML, however, patients enrolled in the current studies will be asked to review and sign an updated consent form.
If you are being prescribed Rituxan® off-label, you should contact your physician with any questions or concerns you may have.
3. Will the study trials for Rituxan® in people with lupus be discontinued?
No. The two reported cases of PML in lupus patients treated with Rituxan® are unrelated to the current clinical research studies of the drug. Rituxan® is not approved by the FDA for the treatment of lupus and the two reported cases represent the off-label use of the drug.
Because of the extremely low occurrence of PML in lupus patients receiving Rituxan® and its occurrence in patients not on Rituxan®, there are no plans by either the FDA or Genetech to put the current studies on hold. PML has not been reported in any of the thousands of patients that have received Ritxuan for rheumatoid arthritis.
Both Genentech and Biogen IDEC will continue to monitor worldwide safety databases for these adverse events.
4. Who is at risk to get PML?
While extremely rare, PML is a known risk factor among people who have severely suppressed immune systems (organ transplant patients, AIDS patients, patients with cancers such as leukemia or lymphoma, patients taking immunosuppressive treatments or patients undergoing stem cell transplantation). There are cases of PML in people with lupus who are not taking Rituxan®, but the contribution of Rituxan® to the development of PML is unknown. While extremely rare in lupus patients, PML appears most likely to develop in older lupus patients that have had lupus for 5 years or longer.
5. Is there a way to test for PML?
The specific factors leading to activation of the latent infection are not fully understood and currently, there is no accepted screening test for PML. Since almost all adults are infected with the latent JC virus, testing for it is not beneficial.
6. What are the symptoms of PML?
Symptoms of PML include mental deterioration, vision loss, speech disturbances, ataxia (inability to coordinate movements), paralysis, and, ultimately, coma reflecting the multifocal distribution of brain lesions. In rare cases, seizures may occur.
In summary, PML is an extremely rare complication in patients with lupus on immunosuppressive therapy. Patients who have received Rituxan® should not be unduly alarmed or concerned, but should discuss any concerns they do have with their physician.