Several new biologics made with cloned cells are getting close scrutiny from the FDA because of the number of patients who have developed a viral infection of the brain which causes a neurological condition called leukoencephalopathy, or PML. The condition results death in less than a year after destroying parts of the brain.
These drugs have been prescribed for psoriasis, HIV, and multiple sclerosis and their use has been spilling over to over autoimmune conditions like Rheumatoid Arthritis, where PML has started showing up.
One of those drugs, Raptiva (efalizumab) was voluntarily withdrawn from the market by the manufacturer in 2009 due to the unacceptable numbers of cases of PML and is no longer available for sale in the U.S. Still inexplicably on the market are several that function the same way and cause the same problem: Tysabri (natalizumab) and, rituximab, sold as Rituxan.
The reaction of some doctors to this news takes my breath away. They say that all this new information gives us a better idea of who can tolerate the drug, therefore they will continue to prescribe it. Before you agree to take it, consider these statements from research studies:
It is currently not possible to identify patients at increased risk for PML before or during … therapy, and there is no known treatment for PML.
Emma Hitt, Efalizumab Withdrawn From US Market
More than half of adults are seropositive for [the virus that causes PML], and in immunocompromised patients, the virus may reactivate and cause PML.
Leukoencephalopathy Linked to Rituximab for RA
Big pharmaceutical companies are in a continuous race to keep those of us with autoimmune conditions like RA supplied with drugs. The problem is that our immune systems refuse to be turned off indefinitely by such poisons and always, sooner or later, find a way to disable them. That’s when our symptoms come back and our doctors tell us we need to try another drug. As the supply of ‘safer’ drugs runs out, all that is left are pharmaceuticals that are increasingly toxic to our bodies.
Eventually each of us will learn that Big Pharma cannot save us. We’ll have to do it ourselves.
Fortunately, we can, by making changes to our diet that stop exasperating our immune systems. Not always an easy solution, as we struggle to find the right and wrong foods, but certain, safe, free and permanent. You will not risk an early death, or worse, by making changes to your diet.
I’ve copied below the heart-stopping reactions of several prominent physicians to the news that PML is a serious consequence of some of the new biololgics. When they say they will continue to use these drugs, I personally, cannot imagine a more cavalier and disrespectful attitude towards us, our bodies and our lives. It’s not as though there are no alternatives.
Be sure to note the financial backing of each of these M.D.s, in italics.
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Clinicians Gain Risk Stratification Tools
Each patient tested who continues to show JCV-antibody positivity well predating the development of PML (with virtually 100% sensitivity and specificity) makes us very confident in terms of putting individuals on therapy who are JCV-antibody negative. It also allows us to take individuals who are positive and focus our research on that smaller subgroup to further identify risk factors for development of PML.
In both camps, it gives us a tremendous step forward in terms of how to manage patients.
As you stratify the risk of these individuals, prior immunosuppression in combination with being antibody positive essentially confers a risk of PML of 8 in 1,000 after they’ve been on treatment for 2 years or more. That’s a relatively high risk.
What that means more than anything else is to really think carefully about how you approach treatment. Do you really want to use an immunosuppressant therapy early on? It’s important to realize that, when we look at the relationship between immunosuppression and PML, it makes no difference when the person received immunosuppression. It could have been 6 months before starting natalizumab or 10 years before. The risk is the same.
An annual MRI may not be frequent enough to catch PML early, but even 6 months may not be frequent enough. What we need are inexpensive quick-scanning methods that allow us to do more frequent scanning. Most of the scanning done in MS is a very costly endeavor. It involves gadolinium-enhancing studies, non-enhancing studies, lots of different pulse sequences. We really need a 5-minute scan that can be done every 3 months on people after they’ve been on therapy for 2 years and in high-risk patients – those who are JCV-antibody positive, for instance.
That kind of scan probably could be done for $200 or less and would not only be cost effective but incredibly useful. The technology doesn’t need to be created; it’s just a question of negotiating with our colleagues in radiology.
Dr. Revere P. Kinkel
Revere P. Kinkel, M.D., is director of the multiple sclerosis center at Beth Israel Deaconess Medical Center, Boston. He has financial associations with Biogen Idec, Novartis, Acorda Therapeutics, and Teva Neuroscience.
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If the assay becomes available, I’m sure I’ll start using it. I think it will be a lot clearer what to do with people who have a negative test and don’t have antibodies, and to be fairly confident that their risk is much lower than the general population of patients with multiple sclerosis. We’re not going to be doing this test on people who have mild MS; we’re going to be doing this in people who have a fairly high risk of bad outcomes if we don’t treat them aggressively.
What will be challenging is the 55% of people who will still have positive results, and what to tell them. Their risk of PML is four times higher than we thought it was, though still small: one in a few hundred instead of 1 in 1,000.
It would be immensely useful to have a rule-out MRI scan for PML versus our current scans to evaluate progression of multiple sclerosis, which is a very fine-cut scan with multiple directions. With the latter, you’re asking for a lot of information you don’t need to diagnose PML. But radiologists have to be comfortable doing that rule-out scan and willing to stand behind it.
Dr. Michelle Cameron
Michelle Cameron, M.D., is a neurologist at Oregon Health and Science University, Portland. She has financial associations with Biogen Idec, Innovative Neurotronics, Teva Neuroscience, DJO Global, Mettler Electronics, and California Education Connection.