In an editorial in Frontiers in Neurology, two leading multiple sclerosis (MS) experts are advocating for genetic testing to identify MS patients who are at higher risk of developing a rare brain infection, called progressive multifocal leukoencephalopathy (PML), as a side effect of their medications.
The two authorities, Joseph Berger, MD, and Hans-Peter Hartung, MD, write, “The availability of a simple, relatively inexpensive test that can identify the genes that put one at risk for PML would be enormously helpful in the management of patients. The widespread use of such testing could potentially allow the clinician to use alternative therapies that do not carry the same risk of PML.”
Berger is the MS Division chief at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, and Hartung is the Neurology chair of Heinrich Heine University in Düsseldorf, Germany, and a specialty chief editor for Frontiers in Neurology.
The editorial was written in support of a recently published study that confirmed a strong link between four genetic mutations and PML. The original study, also published in Frontiers in Neurology, found that these four variants were far more common among patients who took PML-linked drugs and developed PML than patients who took those drugs and did not develop PML.
PML is caused by the JC virus (human polyomavirus 2), which is very common but remains dormant in the vast majority of carriers. However, certain immune-modifying drugs, including those used to treat MS, have been found to induce PML in rare cases.
Drug-induced PML is on the rise as more powerful immunosuppressant therapies are developed. Since 2011, drug-induced PML cases reported to the FDA have more than doubled. And in 2022 alone, there were nearly 600 cases in the FDA’s adverse event reporting system. In that database, over 70 drugs have been linked to PML.
PML patient and Tysabri inventor support genetic testing
"Preventative screening for these variants should become part of the standard of care,” said Lawrence Steinman, MD, whose lab developed Tysabri, a breakthrough MS treatment that carries a black box warning for PML. And when Franklin Jordan, 58, a PML survivor who developed the side effect after taking Tysabri, learned about the availability of the genetic test, he said, “I would have taken the test in a minute. If I knew I was positive, I wouldn’t have taken Tysabri.”
It is expected that preventative screening will become a routine part of patient care, as recommended by Berger, Hartung, and Steinman. But to fill the immediate need, the PML Foundation is currently offering a free test online. Simpler than a COVID swab, the at-home saliva test is processed in a CLIA-certified lab by PreventionGenetics.
Many MS medications currently carry a PML warning, including Tysabri, Ocrevus, and Rituxan, as well as Gilenya, Kesimpta, Mavenclad, Mayzent, Ponvory, and Tecfidera. Not just MS drugs, but medications widely prescribed for blood cancers, organ transplants, as well as autoimmune diseases like inflammatory bowel disease, lupus, and rheumatoid arthritis also include PML warnings on their drug labels.
- This press release was supported by Emerald Lake Safety