Thursday, April 21, 2011

Tyasbri-related PML deaths holds steady at 20%, 111 total cases of PML reported to date

Although good news has been reported regarding a blood test in development by Biogen which tests for antibodies to the JC virus, the presence of which contributes to the development of PML (progressive multifocal leukoencephalopathy) in patients using Tysabri to treat their multiple sclerosis, a steady stream of bad news regarding cases of PML continues to emerge each month.

This month is no exception.  Nine new cases of PML (a rare brain infection) have been reported in patients using Tysabri.  This brings the total up to 111 patients.  Of those, 22 patients (or 20%) have died.  The condition of the remaining 80% is mostly unknown, however a group of patients and family members affected by PML have gathered in Facebook.

The statistics on the risk of developing Tysabri (which changes according to how many infusions one receives) is as follows:
"The most-recent data translate to a rate of 1.99 cases per 1,000 patients on the drug for a year or longer, rising to 2.5 per 1,000 for those on the drug for two years or longer, and dropping to 1.4 for more than three years." 
The FDA has officially updated the label to include:
  • A table summarizing rates of PML with Tysabri use according to the number of infusions (how long the drug is taken or duration of exposure).
  • Information on a newly identified PML risk factor. Patients who took an immune system suppressing medication (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate) prior to taking Tysabri have been shown to be at an increased risk for developing PML. The Tysabri label already warned that using immune system suppressing medications at the same time as Tysabri may increase the risk of developing PML.
It is the fact that I have taken and continue to take methotrexate which prevents me from considering Tysabri for myself as a treatment option.  I first learned of this association from other patients in MS forums more than two years ago.  I'm glad that this information has finally been included officially in the labeling of Tysabri.

Please know that I am not anti-Tysabri.  I am in fact pro-medications-which-help.  Tysabri indeed does help many patients.  I just want to let you know the most recent statistics and reports.

Here is the updated chart including April 2011 data which outlines the number of PML cases reported publicly.

The WSJ report is republished below:

9 new cases of brain infection in Tysabri MS patients

Biogen Idec Inc. has reported nine more cases of a rare brain infection among multiple-sclerosis patients taking Tysabri, sold with Elan Corp, bringing the number of affected patients to 111 as of April 1.

The Weston, Mass., biotech company reported that one more of those patients has died, bringing total deaths to 22. The cases of the infection--known as progressive multifocal leukoencephalopathy, or PML--are closely watched as the MS market becomes increasingly competitive.

The drug is generally regarded as highly effective, but mostly used for patients that have stopped responding to other drugs or have aggressive cases of the disease.

Biogen is developing a blood test to test for antibodies to a specific virus, JC virus, something that may better determine the chances of patients contracting PML. The test recently received CE Mark approval in Europe and the companies are conducting large studies of its effectiveness.

Many people carry JC virus and it causes no harm, but some biologic drugs that modulate the immune system, including Tysabri, appear to promote activation of JC virus in some patients, leading to PML.

European regulators recently recommended the label include language indicating that JC virus antibody status is a PML risk factor. In the U.S., Biogen and Elan have proposed making a similar change.

Also recently, the U.S. label was updated to include the updated incidence of PML.
Regulators monitor cases of PML as they occur and have said that the benefits of the medicine outweigh the risks. Tysabri was withdrawn from the market in 2005 and relaunched in 2006--because of its effectiveness--with a strict access plan that monitors patients.

The overall global PML rate is now at 1.31 per 1,000 patients. Of the total PML cases, 46 were in the U.S., 59 were in the European Union and six in other areas.

The risk of the infection generally increases with the number of monthly infusions that a patient receives, but that rate appears to drop after 30 months. Biogen is studying this drop and has warned there is limited information from patients on the drug longer than 36 months.

The most-recent data translate to a rate of 1.99 cases per 1,000 patients on the drug for a year or longer, rising to 2.5 per 1,000 for those on the drug for two years or longer, and dropping to 1.4 for more than three years.

Looked at another way, the rate is about 1.74 cases per 1,000 patients on the drug for between two and three years. The incidence is about 0.48 case per 1,000 patients in those using it for one to two years, and it is essentially nonexistent in patients using it for less than a year.

Source: The Wall Street Journal Copyright ©2011 Dow Jones & Company, Inc (21/04/11) by way of Multiple Sclerosis Resource Centre (MSRC).


  1. Hi Lisa,

    Thank you for keeping us all up to day with the current stats.

    Would you mind if I linked this over on the MSunderstood facebook page?

    Dana (theMSblog)

  2. Hi Dana,

    Absolutely it's great if you want to link to this. It seems important to document these stats as they are made available. Information can sometimes disappear on the web and I don't want this to be hard for anyone to find.

    Hope you are doing well. :)


  3. Hi Lisa
    Thanks for this.

    I do find yr headline rather misleading - 20% 'of the' 111 would be clearer.

    Also, not sure about 'holding steady', depending on relative to when? My understanding is that in the earlier cases of PML occurring there was a much higher incidence of death. (Not saying that is a good thing, or that 20% of all PML cases is fab either but seems it has changed since Tysab came available.)

    One additional point, regarding those on it for less than one year: while incidence of PML is low, my understanding is that coming off the drug after a short time (eg under a year) resulted in an increased rate of lesions and relapses when the the phase 3 trial was halted for 9 months. Do you know if there is any subsquent more recent information about effects on people stopping treatment within particular time frames available?

    Not sure if the statistics about PML relative to JC virus are publically available but as participant in the study, I was informed that if I do not have JC virus then risk of PML is negligble.