Rare infection occurs in patient on Tecfidera

October 24, 2014
On Tuesday, October 21, 2014, Biogen announced that a patient treated with Tecfidera developed a rare infection, progressive multifocal leukoencephalopathy (PML). This patient was from Europe and had been treated with Tecfidera for 54 months. For approximately 3 ½ years, this person’s lymphocyte counts were very low, in the 200-500/mm3 range. After an illness lasting about 4 months this patient died from complications of the infection.
 
PML is an infection caused by the JC virus. About half of the population has the JC virus. Once a person has the JC virus, the immune system quickly brings it under control, but the virus remains hidden in the kidneys after that. From the kidney, the virus can periodically flare up and the immune system quickly brings it under control again. There are many other viruses that have this ability to periodically flare up, for example a virus that remains hidden in the nerves of the face can periodically flare up causing fever blisters, or chicken pox virus remains hidden in the nerves and can periodically flare to cause shingles. The JC virus is fairly easy for the immune system to control, and it generally does not cause medical problems. The one exception is PML.
 
PML occurs when the JC virus flares up in a person whose immune system is not normal. In this setting the virus can spread from the kidney to the brain where it causes widespread damage and usually death. This can happen with a number of immune system diseases, or with prolonged courses of chemotherapy. In recent years PML has occurred with other medications that block the immune system.
 
Tecfidera has been a very successful medication used to treat multiple sclerosis. However, it can cause a decrease in the white blood cells and lymphocytes in the blood. This decrease is usually about 30, which is a level that would not be concerning. Unfortunately, about 6% of patients on Tecfidera have a lymphocyte count less than 500 and less than 1% have lymphocyte counts less than 200. Levels less than 500 increase the risk of infections and those less than 200 have an even higher risk of infection. Until this case of PML, Tecfidera did not have any increase in the risk of getting infections.
 
I believe that the cause of PML in this case was the very low lymphocyte levels that were prolonged for several years. It is important to realize that most patients on Tecfidera do not need to worry about infections. The patients that are at risk of infection are those whose lymphocyte counts are less than 500. We recommended checking lymphocyte blood counts on patients on Tecfidera every 3 months. Those that have very low lymphocyte levels that persist over a few months would need to consider switching to another medication. Those that have lymphocyte levels above 500 should not be at risk of PML.

If you have a question about your medication, please talk with your healthcare provider.