MS Patients Treated with Natalizumab at Risk for Rare Disease
Use of natalizumab in people with multiple sclerosis (MS) seems to be linked to an infection (JC virus) that can result in the development of a rare, lethal disease called progressive multifocal leukoencephalopathy (PML), according to a new report. The findings of this study, which appears in JAMA Neurology, may help researchers better understand why some people with MS develop this deadly disease.
So far, no other drugs used to treat MS have been associated with PML, but more than 440 people with MS have been diagnosed with the disease since 2006, when natalizumab (Tysabri) was brought to the market for MS. That was the second time the drug was introduced; it was initially approved in 2004 but was withdrawn after it was linked with three cases of PML when taken along with interferon beta-1a, a common treatment approach for MS.
Risk factors for PML include:
- Use of natalizumab, especially if you have received 24 or more treatments (one infusion per month is the typical protocol)
- Exposure to JC virus (John Cunningham virus), a common virus present in about 75 percent of the general American population. However, the virus rarely causes any symptoms except in a small percentage of people with MS. A blood test can provide evidence of exposure.
- History of use of azathioprine, cyclophosphamide, methotrexate, mitoxantrone, or other drugs that can weaken the immune system
- History of HIV, AIDS, leukemia, lymphoma, or another condition that can severely suppress the immune system
PML is a rare, incurable viral infection that results in death or severe disability. The disease is caused by the JC virus and is characterized by widespread inflammation of the brain.
Although healthy individuals often carry the JC virus, their immune system keeps it in check. However, when the immune system is compromised by disease (HIV/AIDS) or certain medications (e.g., natalizumab, efalizumab, among others), the virus can run rampant.
New natalizumab study
In the new study, investigators evaluated blood samples of 49 individuals with MS and 18 healthy subjects for levels of CD34+, CD19+, and CD3+ cells. CD34+ cells are involved in cell migration, CD19+ cells have been implicated in autoimmune disease (e.g., MS), and CD3+ cells are often the target of immunosuppressive therapy.
Of the 49 patients, 26 were beginning treatment with natalizumab, and these individuals had blood samples taken every three months until month 10. In addition, blood samples were collected from 23 patients with MS who had been taking natalizumab for more than two years.
The researchers discovered that:
- 13 of the 26 (50%) MS patients who had just started natalizumab treatment had identifiable JC virus DNA
- 10 of the 23 (44%) of MS patients who had been taking natalizumab for two years or longer had detectable JC virus DNA
- 3 of the 18 (17%) healthy subjects had detectable JC virus DNA
- 15 of the 49 (31%) MS patients had JC virus in CD34+ cells and 12 of the 49 (24%) had the virus in CD19+ cells
The presence of JC virus DNA in both CD34+ and CD19+ cells is a telling find. According to the authors, natalizumab “triggers the mobilization of cells potentially infected with JCV into the circulation.” They also noted that “Cells with latent infection initiate differentiation to CD19+ cells that favor growth of JCV.”
The findings of this study contribute important information to the literature on the link between natalizumab, JC virus, and PML in patients with MS. Individuals with MS who are considering use of natalizumab should discuss the risks of PML with their healthcare provider.
Natalizumab treatment in patients with multiple sclerosis associated with JC virus infection. JAMA Neurology 2014 Mar 24 online