Anonymous Docs speaking the truth?

When you are anonymous, you are disinhibited… just like me! 
You will say things you wouldn’t normally say…just like me!
Sounds like a Pussycat Dolls song

Dr.Dre is one of our Bloggers who sometimes speaks reason and sometimes speaks….rap. He often likes to sing that “them drugs are bad”…which is a bit rich coming from a rapper:-).

However, remove the name and the prospect of not getting a freebee to ECTRIMS what will the Docs say…..

It seems there are a few DoctorDres out there, but I wonder if they are just a Do nothing, “Used-Wheelchair sales man/woman).

Prescrire International is the concise, English language version of la revue Prescrire. Prescrire International is a unique source of independent comparative information on drugs and other therapeutic interventions. The New Drugs section provides you with comparative assessments of new drugs and news indications. The Reviews section gives you assessments of therapeutic interventions as well as treatment guidelines that will help you to offer your patients effective care based on the best availabe evidence. The Adverse Effects section gives you a balanced view of the latest suspected or confirmed adverse drug reaction data collected from the many published and unpublished data sources all over the world.

So “sacre bleu” what do they say

Alemtuzumab (LEMTRADA) and multiple sclerosis. Biased evaluation, evidence of serious risks. Prescrire Int. 2015 Mar;24(158):69.
As of late 2014, interferon beta injection was the standard “disease-modifying” treatment for patients with relapsing-remitting multiple sclerosis, in the absence of a better alternative. Alemtuzumab (Lemtrada), an anti-lymphocyte monoclonal antibody first used in some types of leukaemia, is authorised in the European Union, at a different dosage, for patients with multiple sclerosis. Clinical evaluation in multiple sclerosis is based on three unblinded trials comparing alemtuzumab with interferon beta-1a. These trials were all biased in favour of alemtuzumab and thus fail to establish the potential value of this immunosuppressant. Overall, adverse effects, including the most severe, were more frequent with alemtuzumab than with interferon beta-1a. The adverse effects of alemtuzumab reported in these trials had already been observed in cancer patients. They included potentially severe reactions to the infusion, as well as a risk of infections and cancer due to profound and prolonged immunosuppression. At the dosage authorised in multiple sclerosis, autoimmune disorders such as thyroid disorders and immune thrombocytopenic purpura are particularly frequent and serious. In practice, patients with multiple sclerosis already have difficulty coping with the troublesome consequences of their underlying disease. They should not be subjected to the serious adverse effects of alemtuzumab, especially given the absence of any proven benefit.

Having looked how to blind a trial to Alemtuzumab, to include dummy infusions, steroids, anti-virals and the reviewers said they did not believe it was possible to blind an alemtuzumab trial

So if this is true and someone won’t believe a trial unless it is blinded then is this and many other drugs are doomed. 
There are characteristic side effects with most drugs. So should we throw them away too?

So if you can’t blind, is a drop in the relapse rate and all the other benefits of Alemtuzumab just imagination of the MSers? 
Surely if that were the case Beta Interferons and Glaterimer acetate would have done even better in the trials many years ago. 
I don’t think the blinded assessors thought so in the case of Alemtuzumab.

So if we are so big on blinding maybe we have to get big on the assessors so that only the same assessors are used on each person because if they don’t then there can be more subtle differences on the effects of EDSS. I heard Dr.C/ProfC say that if you remove the centres what had multiple EDSS raters from the CARE (Phase III) studies, then the results got so much better.

As to the side-effects of Alemtuzumab they have indeed been reported for some time and maybe had the Docs from C been less Gung-Ho then they may have stopped when signs got worse after infusion. Maybe they thought they were developing a £800 drug not a £56,000 drug, and were giving MSers an option and a choice.

 However it is clear that it may not be the choice of the MSers as some Neuros have decided Lemtrada is a risk too far.

To say that Alemtuzumab has not proven benefit suggests they have got their head some where dark:-) 

The standard disease-modifying treatment for patients with relapsing-remitting multiple sclerosis is interferon beta injection, in the absence of a better alternative. In 2007, natalizumab had an unfavourable harm-benefit balance in patients with severe multiple sclerosis in whom interferon beta was ineffective, due to insufficient evidence of efficacy and a risk of life-threatening progressive multifocal leucoencephalopathy. In 2014, we found no new comparative trials focusing on the efficacy of natalizumab monotherapy in its authorised indications in the EU. Post-marketing data confirm the adverse effects identified in clinical trials, including serious and life-threatening opportunistic infections, particularly progressive multifocal leucoencephalopathy in about two per thousand treated patients (an incidence twice as high as initially estimated), and potentially severe hypersensitivity reactions. An increased risk of cancer in the long term cannot be ruled out. Post-marketing data also show that natalizumab can cause severe liver damage. In addition, natalizumab withdrawal because of progressive multifocal leucoencephalopathy almost always triggers an immune reconstitution syndrome that can lead to neurological complications or even death. In practice, regardless of the severity of multiple sclerosis, it does not seem reasonable to expose patients to the many serious adverse effects of natalizumab for such an uncertain benefit.

It is true that when PML first reared its head the risk of PML was thought to be about 1 in 1000 and according to Biogen it has indeed crept down to about 1 in 100. Some people may argue that because people are switching off Natalizumab the denominator has been removed and so the risk is even higher. 

There is no question that tysabri is a very active drug, especially if you are JC virus negative, but the issue is how to stop and switch to something else. ProfG has done many many posts on this but it is the case for a JC virus positive person taking Tysabri that they have to think about the risk of PML which kills about 20-25% of people affected and leaves the others with a lot more disability. 

So next up we have Aubagio:

Teriflunomide (AUBAGIO). Multiple sclerosis: just a metabolite of leflunomide.Prescrire Int. 2015;24:61-4.

In mid-2014, subcutaneous or intramuscular interferon beta injection is the standard disease-modifying treatment for patients with relapsing-remitting multiple sclerosis, in the absence of a better alternative. Teriflunomide, the main active metabolite of leflunomide, has been approved as an oral treatment in this setting. Both substances have immunosuppressive effects. Clinical evaluation of teriflunomide is based on a comparative trial versus interferon beta-1a in 324 patients and on two placebo-controlled trials in a total of about 2300 patients lasting 1 to 2 years. In these trials, oral teriflunomide at a dose of 14 mg per day led to a statistically significant decrease in the average annual number of relapses compared to placebo, but teriflunomide may be less effective than interferon beta. No impact on the progression of disability has been shown during less than 2 years of follow-up. The burdensome adverse effect profile of teriflunomide is similar to that of leflunomide and includes hepatotoxicity, infections, leucopaenia, arterial hypertension, peripheral neuropathy and alopecia. The long half-life of teriflunomide (about 19 days) complicates the management of its adverse effects and multiple drug interactions, and has important implications for patients wishing to have children. Teriflunomide is teratogenic in animals and should not be used by pregnant women. Foetal toxicity via semen cannot be ruled out. In practice, the adverse effects of teriflunomide in multiple sclerosis are disproportionate to its efficacy. It is better to choose interferon beta, despite its limitations

So lastly the new kid on the weak DMT block, it is about as effective as beta interferon but it is a pill. This study suggests it is a bitter pill to swallow as it may cause birth defects, headaches and hair thinning which is not what you really want if you are a young person with MS.

It is true that all MS drugs have side-effects, some more than others and different levels of efficacy, some more than others. So more reason why it is time for a rethink about cladribine. Is it’s side-effect issue a real problem that puts it at as much riskier than these current drugs.

However, it is wrong to suggest that MS drugs are all bad. They are not, it has put MS on the map and Pharma interest in MS has brought enormous benefit.

So a set of three posts by anonymous, I wonder if this is really Dr.Dre. If this was not anonymous, would it be Doc Dead in a ditch:-).

CoI Multiple

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  • Who says that Prescrire is a unique independent comparator of drugs? Is it Prescrire itself? How do we know that the 'doctors' involved aren't all working for the makers of the old injectables? What about those who have had Lemtrada and haven't relapsed for 9 years- that's a long time for the placebo effect to last. I would change neuro if he was dr. patronising who wouldn't give me a licensed drug because he didn't believe in it.

  • Dre is the greatest thing to happen in MS. His comments are my favourites. Proper entertaining. He's like thé Russell Brand of multiple sclerosis.

  • I agree with you MD. Everything in life can have a "side effect", too much water can cause hyponatremia, until vitamins that are regarded "as possible treatments for MS has its side effects: vitamin D3 at high doses can cause kidney failure, Biotin in high doses may be teratogenic and cause disorders of the thyroid … I know particularly a guy who made experimental use of Alemtuzumab in Brazil in 2008 and he is very well without relapse without disease progression, having a totally normal life even (before MS was very active, many outbreaks, etc.)… I know Natalizumab users who there are at least 05 years to use fine with their doctors performing tests for the presence or absence of JC virus constantly …

  • These kind of studies really rub me the wrong way. We are all on a drug called "multiple sclerosis" that has an almost 100% chance of side effects that include numbness, muscle spasms, blurred visions, difficulty controlling emotions, bladder and bowel problems, unemployment, divorce, bladder and bowel problems, brain damage, blindness, paralysis, and so on.

    Am I lining up to roll the dice on getting PML, melanoma, thyroid problems, or whatever else? Of course not. But many of us are willing to take a small chance of these things occurring for the potential to live a normal live. I am a grown adult, and I will make my own decision on what risks to take with my treatment. Prescrire can take their recommendations and stick them up their rear.

  • I think it is important for MS patients to understand that their neurologists can be well intentioned and still recommend something that is not in the best interest of the patient.

    The doctor is approaching the patient with an aim of minimizing the impact of MS – the patient is looking out for their overall well being. I switched from Copaxone to Tecfidera after about 10 nearly relapse free years because I was seeing some progression.

    My doctor considered the Tecfidera a smashing success as my MRI stabilized and I seemed to level out clinically as well. However I developed lymphopenia and decided to switch back to Copaxone.

    From the doctors standpoint this seemed a shame – Tecfidera was working well on my MS. However I made it 10 years on Copaxone and have only progressed to an EDSS of 2.0. I would rather risk a slow decline in function than potential ramifications of a compromised immune system. The patient has to weigh the risks and rewards. The doctor is an advisor but should not be the decision maker.

  • REALLY??
    Use of multiple sclerosis medicine Lemtrada restricted while PRAC review is ongoing
    “EMA’s safety committee (PRAC) has started a review of the multiple sclerosis medicine Lemtrada (alemtuzumab) following new reports of immune-mediated conditions, which are caused by the body’s defence system not working properly, and problems with the heart and blood vessels with this medicine, including fatal cases.

    While the review is ongoing, Lemtrada should only be started in adults with relapsing-remitting multiple sclerosis that is highly active despite treatment with at least two disease-modifying therapies (a type of multiple sclerosis medicine) or where other disease-modifying therapies cannot be used. (….)”



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