On December 19, 2006, the United States Food and Drug Administration issued an “Alert” regarding the safety of Rituxan use in patients suffering from rheumatologic illnesses.
This alert was issued because there were two reported cases of fatal Progressive Multifocal Leukoencepholopathy, more conveniently referred to as PML. And while these two patients were lupus patients, doctors are being warned to be alert to the possible development of PML in any patient being treated with Rituxan.
PML is a rare and usually fatal affliction of the central nervous system caused by reactivation of a virus known as the JC virus. Most people are carriers of this virus (by some estimates, 80% of healthy adults). However, PML only affects a small minority, perhaps 1 in 200,000; and these unfortunate patients are generally those whose immune systems are extremely dysfunctional, such as AIDS patients or patients taking large amounts of immunosuppressive medications.
To put into perspective how rare PML is, it is worthwhile to look at the experience of Rituxan in patients being treated for lymphoma and other types of blood malignancies: As of December of 2006, 23 cases of PML had been reported after Rituxan treatment, and most of these patients had received other chemotherapy for their disease; in contrast, over 900,000 cancer patients have been treated with Rituxan.
Even more interesting is the fact that there have been approximately 20 reported cases of PML in lupus patients NOT receiving Rituxan; almost 90% of these individuals were receiving immunosuppressive drugs. The fatality rate was almost 70%. There have been a few reports of PML in rheumatoid arthritis patients—but NO reports of PML thus far in rheumatoid arthritis patients being treated with Rituxan.
PML usually is manifested as a weakness of certain parts of the body, difficulty thinking, and difficulty with coordination. An MRI can help with the diagnosis. A spinal tap can allow for testing for the JC virus in the spinal fluid. The treatment is problematic and often not very successful. One anti-viral drug, cytarabine, has some activity against the JC virus, but unfortunately this medication does not penetrate into the central nervous system very effectively.
Of course, the rheumatoid arthritis patient who is being treated (or will be treated, or has been treated) with Rituxan wants to know the bottom line: “What does all this mean for me?” And I think the best answer can be derived from what I tried to convey in this brief communication: PML is rare, but the overall short-term and long-term risk is not yet established. As we all know too well, every treatment has its potential side effects; but we also know that allowing aggressive rheumatoid arthritis to go unchecked lowers both the quality of life—and the duration of that life. It will be important for rheumatologists to report any cases of PML in their Rituxan-treated rheumatoid arthritis patients to the FDA. We will all have to wait to see whether PML will be a confirmed side effect of Rituxan use in rheumatoid arthritis, or just one more rare potential complication of ANY treatment which alters the immune system in the fight against a debilitating disease.
Published On: January 31, 2007