Screening? Maybe
In a press release, Lawrence Steinman, MD, from Stanford (Calif.) University, who was not involved in the study, stated that “preventative screening for these variants should become part of the standard of care. I wish we had more powerful tools like this for other therapies.”
But another neurologist who was not involved in the study commented that the finding, while “exciting” as a confirmation study, is not as yet practice changing.
“It does give us very good confidence that these four genes are indeed risk factors that increase the risk of this brain infection by quite a bit, so that makes it very exciting,” said Robert Fox, MD, from the Neurological Institute at the Cleveland Clinic.
“Indeed, we are trying to risk-stratify patients to try to reduce the risk of PML in the patients treated with our MS drugs. So for natalizumab we risk stratify by testing them for JC virus serology. Half of people don’t have it and we say ‘OK, you’re good to go.’ With other drugs like Tecfidera – dimethyl fumarate – we follow their lymphocyte counts, so when their lymphocyte counts drop too low we say ‘OK, you need to come off the drug because of the risk of PML,’ ” he said in an interview.
The four-gene signature, however, only identifies about 11% of patients with PML, which is not a sufficiently large enough effect to be clinically useful. For example, the risk for PML in patients treated with natalizumab is about 1%, and if the test can only detect enhanced risk in about 11% of those patients, the risk would drop from 1% to 0.9%, which “doesn’t really the move needle much,” he pointed out.
Dr. Fox also noted that neurologists now have a large formulary of drugs to offer their patients, including agents (such as interferon-beta and corticosteroids that are not associated with increased risk for PML).
The study was funded by Emerald Lake Safety and Population Bio. Dr. Hatchwell and several coauthors are employees of the respective companies, and several are inventors of genetic screening methods for PML. Dr. Steiman has disclosed consulting for TG Therapeutics. Dr. Fox reported consulting for manufacturers of MS therapies.