By Dennis Thompson
The ingredient, dimethyl fumarate, appears to have contributed to the deaths of two European women. The women contracted progressive multifocal leukoencephalopathy, or PML, according to two letters published in the April 9 issue of the New England Journal of Medicine.
One case involved a 54-year-old woman with multiple sclerosis. She died in October 2014 from complications related to PML and pneumonia, following 4.5 years of treatment with a time-delayed form of dimethyl fumarate carrying the brand name Tecfidera, researchers reported.
The second case was a 64-year-old woman with psoriasis. She died in August 2014 from PML after being treated with a delayed-release dimethyl fumarate compound with the brand name Psorinovo for two years, according to the researchers.
These cases follow reports linking other drugs containing dimethyl fumarate with PML, including Tysabri and Fumaderm, the researchers said.
However, the latest case reports do not prove that dimethyl fumerate caused the PML infections.
"It's something to be concerned about and something to pay attention to. But from what we know right now, the occurrence of PML appears to be pretty low for Tecfidera," said Bruce Bebo, executive vice president of research for the National Multiple Sclerosis Society.
PML is caused by the JC virus, which normally lies dormant in most people's bodies and causes no harm. But if a person's immune system becomes compromised, the JC virus can flare up and attack the white matter of the brain.
The JC virus strips nerve cells of their insulation, robbing them of their ability to effectively carry brain signals. The disease causes progressive weakness, paralysis, changes in vision and speech, and problems with thinking and memory.
Based on these reported cases and other studies, doctors believe that dimethyl fumarate may affect a person's immune system if taken for an extended period, potentially opening the door to PML.
"I would certainly say this has made me feel like I would follow a patient's white blood cell counts," said Dr. Abby Van Voorhees. She is chair of the National Psoriasis Foundation Medical Board and an associate professor of dermatology at the University of Pennsylvania's Perelman School of Medicine, in Philadelphia. "If your counts are low, they make you more vulnerable to infection in general. Since PML is an infection, it would make you more susceptible to that as well."
More than 135,000 MS patients in the United States have been treated with Tecfidera since its approval in March 2013, according to the NEJM letter, which was co-authored by a doctor from the drug's maker, Biogen.
"This is the single case of PML associated with Tecfidera," Biogen said in a written statement. "Based on experience in over 135,000 patients with MS treated with Tecfidera, there is no overall increased risk for serious infections, including opportunistic infections, for Tecfidera."
Bebo and Van Voorhees said they see no reason for patients to stop taking drugs containing dimethyl fumarate, as long as their doctors keep close watch on their white blood cell counts and pull them off the medication if their counts drop.
"Doctors have to know that's a risk factor," said Dr. Karen Blitz, director of the North Shore-LIJ Multiple Sclerosis Center in East Meadow, N.Y. "If you know that, you can carefully use the drug. It appears that if you watch the white cell counts, you can protect patients who may be predisposed to develop PML on this medication."
Blitz, who is a consultant for Biogen, noted that the MS patient who developed PML had been taking a higher-than-usual dose of Tecfidera and also had suffered from an extended period of low white blood cell counts.