Tecfidera and PML: Is there a direct connection?

Patient Expert

How important is it to you to have full access to the same information neurologists do when it comes to medications, clinical trials, and post-marketing data from a pharmaceutical company?   Or full access to your medical files which include medical history, doctor's notes, and testing results complete with reports?

As patients living with chronic illness, we are arguably the experts in our experience living with MS.   Our neurologists, especially those who specialize in MS, are the experts in evaluating our medical needs and play an important role in providing access to appropriate testing and treatment.   MS is so very complicated that neurologists have a very important job to do.

I know that I trust my neurologist and my medical team, which includes a neurologist, nurse practitioner, MS nurse, and infusion nurse, to have my best interests in mind when we make decisions.   I also always get copies of all MRI reports and laboratory test results for my own understanding and personal files.   I want to know what is going on and what it all means.

When headlines hit the news such as last week's announcement that cases of PML have occurred with a medication containing the same active ingredient as Biogen Idec's newly approved Tecfidera (BG12, oral dimethyl fumarate), I have a need to know the whole story.   Fortunately, I was able to access the case studies and company's response published in the New England Journal of Medicine (NEJM).

Only weeks following the approval of Tecfidera (oral dimethyl fumarate), also known as BG-12, for the treatment of relapsing forms of multiple sclerosis, the headlines have been scattered with mentions of PML, or progressive multifocal leukoencephalopathy.

In the April 25, 2013 issue of the New England Journal of Medicine (NEJM), two separate cases involving patients in Europe diagnosed with psoriasis who developed PML while taking different forms of dimethyl fumarate.   Dimethyl fumarate is the active ingredient found in Fumaderm® (fumaric acid esters) tablets and Tecfideraâ„¢ (dimethyl fumarate) delayed release capsules made by Biogen Idec.   The cases studies are described in Letters to the Editor in NEJM with a response provided by Biogen.

So often, medical articles are kept behind pay walls, meaning that to access the article you must be a subscriber to the journal or pay a hefty fee to download the article online.   I appreciate it when I can read open access articles, or in this case correspondence in NEJM.

Fumaderm has been used for 19 years in Europe to treat moderate-to-severe plaque psoriasis psoriasis, a chronic autoimmune disease which affects the skin.   Biogen reports that there have been a total of four psoriasis patients who have developed PML in more than 180,000 patient-years of experience with the drug.   In contrast, as of April 5, 2013, there have been 347 cases of PML in MS patients taking Tysabri since 2008.   There were NO cases of PML noted in patients taking Tecfidera (BG12) during clinical trials.

PML is a serious brain infection caused by the reactivation of the JC Virus in patients who are immunosuppressed, primarily due to drug treatment or disease.   Signs of PML include neurological symptoms which can be mistaken as MS symptoms.   Risk factors for PML include presence of JC virus antibodies in the blood or cerebrospinal fluid and immunosuppression (often by use of certain medications).

For more information regarding the PML cases with Fumaderm and a compounded version of the same drug, here is an article I wrote on the subject - Tecfidera and PML: What's the Story?   I'll say it again - there were NO cases of PML noted in patients taking Tecfidera (BG12) during clinical trials.

I like to be able to read the articles myself.   Having access to the same information which doctors do is important to me.   I prefer to be able to read the source directly rather than waiting for an office visit to have the information interpreted for me.

Do you ever read/download articles from medical journals?   If so, what are you favorite go-to resources for such articles?

Read the Letters to the Editor here:
Angel P. Sempere AP, Berenguer-Ruiz L, Khabbaz E.   Oral BG-12 in Multiple Sclerosis. N Engl J Med 2013; 368:1652-1653 April 25, 2013 DOI: 10.1056/NEJMc1212740

Ummehan Ermis U, Weis J, Schulz JB.   PML in a Patient Treated with Fumaric Acid. N Engl J Med 2013; 368:1657-1658. April 25, 2013 DOI: 10.1056/NEJMc1211805

van Oosten BW, Killestein J, et al.   PML in a Patient Treated with Dimethyl Fumarate from a Compounding Pharmacy.   N Engl J Med 2013; 368:1658-1659 April 25, 2013 DOI: 10.1056/NEJMc1215357

Sweetser MT, Dawson KT, et al.   Manufacturer's Response to Case Reports of PML.   N Engl J Med 2013; 368:1659-1661 April 25, 2013DOI: 10.1056/NEJMc1300283