How quickly should we treat MS?
DrK makes the case for treating everyone as quickly as possible. Do you agree? Can you help us convince Biogen about the case for a Brain Attack Trial?
When we were at the ECF meeting in Baveno DrK came up with a very important trial design to maximise the protection of the brain in MS. We all know that ‘Time is Brain’ and most MSologists will have patients who have had catastrophic relapses whilst waiting for a diagnostic workup and/or DMTs. We also know that MS activity tends to be clustered, i.e. one of the best predictors of a relapse is a recent relapse. Instead of putting patients with possible early symptomatic MS at risk from having to wait why don’t we to treat them all with natalizumab to protect their brains and spinal cords? This is analogous to treating stroke.
Why natalizumab? It is one of our most effective DMTs, it works very quickly, it is given as an IV infusion, hence there is no problem with adherence and is very safe for up to 12 months. It is also relatively safe in pregnancy. During this 12 month period, the neurologist and the patient can then decide what strategy they want to pursue in the long-term. This could be to continue natalizumab long-term or to switch to another DMT, or in the case of an alternative diagnosis the drug can be stopped.
To make the Brain Attack Trial a reality we would have to get Biogen to ask the EMA to license natalizumab as a 1st-line treatment. This may require data. Hence we are proposing that Biogen sponsor a ‘Brain Attack Trial’. This would become even more important if you can derisk the PML problem associated with natalizumab. Imagine if we can reduce the risk of PML to zero? Who wouldn’t want to start on natalizumab as a first-line therapy? Natalizumab will become the one and only platform therapy. The problem with this is that Biogen has other DMTs in the MS space and the Brain Attack Trial will potentially result in natalizumab cannibalizing their other DMT market. How bold is Biogen?
I can’t resist a business anecdote. Sony invented the Walkman, which transformed the way we listen to music. Sony then developed a digital version of the Walkman, i.e. their version of iPod. This was done a decade before Apple launched the iPod. However, Sony blinked and you should never blink in business. The issue was that Sony also produced content via Sony Music and other record labels (e.g. Columbia Records) and as a result of this Sony Executives decided it was too risky to launch the digital Walkman and decided to keep it under wraps and mothball it. Sony was worried that a digital Walkman would fuel digital piracy and cannibalize the music industry. Fast-forward a decade an Apple launches the iPod, which transforms the music industry, kills the Sony Walkman, revitalises Apple and the rest is history.
Sony was the one company, outside of Apple, Steve Jobs admired and feared most. Have you compared the recent fortunes of Apple and Sony? Joseph Schumpeter, the famous economist, calls this creative destruction.
The moral of this story is that if Biogen doesn’t do this study another company will and Biogen will run the risk of becoming the Sony of the MS world; first admired, then envied and finally irrelevant.
ProfG
.fa {
padding: 10px;
font-size: 20px;
width: 20px;
text-align: center;
text-decoration: none;
margin: 5px 2px;
border-radius: 50%;
}
.fa:hover {
opacity: 0.7;
}
.fa-facebook {
background: #3B5998;
color: white;
}
.fa-twitter {
background: #55ACEE;
color: white;
}
.fa-google {
background: #dd4b39;
color: white;
}
.fa-linkedin {
background: #007bb5;
color: white;
}
.fa-youtube {
background: #bb0000;
color: white;
}
.fa-instagram {
background: #125688;
color: white;
}
.fa-pinterest {
background: #cb2027;
color: white;
}
.fa-snapchat-ghost {
background: #fffc00;
color: white;
text-shadow: -1px 0 black, 0 1px black, 1px 0 black, 0 -1px black;
}
.fa-skype {
background: #00aff0;
color: white;
}
.fa-android {
background: #a4c639;
color: white;
}
.fa-dribbble {
background: #ea4c89;
color: white;
}
.fa-medium {
background: #000000;
color: white;
}
.fa-tumblr {
background: #2c4762;
color: white;
}
.fa-vine {
background: #00b489;
color: white;
}
.fa-foursquare {
background: #45bbff;
color: white;
}
.fa-stumbleupon {
background: #eb4924;
color: white;
}
.fa-flickr {
background: #f40083;
color: white;
}
.fa-yahoo {
background: #430297;
color: white;
}
.fa-soundcloud {
background: #ff5500;
color: white;
}
.fa-reddit {
background: #ff5700;
color: white;
}
.fa-rss {
background: #ff6600;
color: white;
}
Why not start everyone with MS on generic cladribine…now that would be a technological revolution.
Good thought, but natalizumab is more easily reversible and it is a very good drug especially if your are JC negative.Good to see DrK thinking out of the box again
We are talking about starting natalizumab within hours of presenting with your first attack. With cladribine you would need to check baseline bloods and an infectious screen that includes HIV, Hep B & C, VZV, TB elispot, syphilis, cervical smears, etc. With natalizumab you would make sure the routine emergency bloods are okay and you would start the infusion. In other words natalizumab in MS would be equivalent to thrombolytic therapy in stroke.
What is a safe time to wait after being diagnosed or relapse before starting treatment? I don't mean years but like 3 months? 6 months? I ask because straight away seems slightly extreme to me
What I find scary is the real risk of serious rebound when Natalizumab has to be stopped plus the increasing risk of PML the longer you are on it. Cladribine may be less effective but surely its more attractive safely profile as well as the convenience (plus reduced cost for NHS) of taking an oral tablet at home makes it a better choice? I remember reading a comment made by Dr G about him losing sleep over the possibility of premature ageing with the use of Natalizumab (from a post written in September 2012: 'Grand challenges in MS -6'). What drug could you safely take after stopping Natalizumab to avoid long term use/risk?
You would just stop natalizumab; you would transition them onto another therapy. The latter could be oral cladribine, ocrelizumab, fingolimod, etc. Or if you were JCV-negative you can stay on natalizumab.
"We are talking about starting natalizumab within hours of presenting with your first attack"Not even a diagnose and allready a dmd?Those your first attack = Ms diagnose?Obrigado
As Prof G says Cladribine cells kills slowly, that's why it does not cause infusions reactions
This trial will also help convince the MS community that we should treat MS actively and not passively. I hope you agree.
Why not ocrelizumab? Safer and like you said no tests required. And if barts patient selection theory is correct. Most effective? But yes. Quicker the treatment. Better the outcome. Regardless brain/Spinal reserve.
Why not ocrelizumab? You can't reverse ocrelizumab, therefore you would need to be confident of the diagnosis and you would have to do some tests and wait for the results.
Biogen will never buy into this strategy. They are divesting from MS and investing in Alzheimer's, Parkinson's and other diseases. Natalizumab sales are flat and falling. They stand to make a lot of money from Ocrevus and hence are getting out of Genentech's way.
You may be right about divesting. But at the moment Biogen is still an MS company and they need to reflect on that.
What do you have to say about these cases?Catastrophic brain relapse in seronegative NMO after a single dose of natalizumabhttps://www.ncbi.nlm.nih.gov/pubmed/24576801Natalizumab, an effective treatment for MS, has been shown to exacerbate neuromyelitis optica (NMO) with aquaporin-4 antibodies (…)Without confirmed diagnosis MS drugs can be dangerous to NMO and probably many other possible causes of neurologiacal manifestations that remind MS. RTX could be a safer option for such cases, but not all CIS patients turn to actual have MS, so it would be a shame to live in drugs that you dont need because you were too precautious. Why this patient spent 4 years without close monitoring??
I am not sure that natalizumab promotes relapses but it is questionable whether it stops them https://www.ncbi.nlm.nih.gov/pubmed/28642888https://www.ncbi.nlm.nih.gov/pubmed/22332191https://www.ncbi.nlm.nih.gov/pubmed/21868485
Seriously MD?"In at least one case series and two further case reports, a total of six NMO patients presented continuous relapses or even a deteriorating disease course under natalizumab, [6,9-11]. Subsequently, these observations were controversially discussed in the neuroimmunological community [12]. Our case adds further evidence to the notion that natalizumab, while highly effective in MS, may not work sufficiently in NMO. Indeed, natalizumab does not positively affect the trafficking properties of neutrophils, which are abundant in NMO lesions. After natalizumab therapy, an increase of B-cell precursors in the blood is observed, which might be counterproductive in case of a presumed B-cell-based pathomechanism as in NMO [13,14]."https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046517/This approach is already quite extreme and you still want to push it after these reports? We said hit hard from the start, not hit blind and no matter what.I only feel bad because I had an intense argument with an NMO patient who was telling me that doctors still know nothing on NMO. And I believe NMO will not be the only problem with Natalizumab.
"natalizumab, while highly effective in MS, may not work sufficiently in NMO."Isn't that what the references I supplied said? Thats what I thought they said
NMO is not a contraindication to the #BrainAttack trial. All you would need to do is exclude the diagnosis; you would have NMO as one of the exclusion criteria.
I thought you did't want to wait for the lab results since it would happen within the first hours of the attack. Why not just follow the Mc Donald criteria? Anything else is dangerous in many ways -immune suppression can be bad for bacterial causes like Lymes d. (for Rituxan that I mentioned).Also, MS is a chronic disease, one can wait a little to get a final diagnose and it is not often to have a second attack that close to the first one, especially with prednisone.The "i have a dream" about the antiviral for JCV is funny for us patients, because it didn't happen when it was mostly needed with no O. around and now it just looks like investing to that, would mean that we are stuck with that, as an approach.I am a fan of the hit hard from the start but I am totally opposite to do it without the diagnostic criteria. MS drugs are not an aspirin to hit once and safely.
There news of simple blood test that can diagnosis MS very quickly. Is this more fake news? If not then is this not irrelevant? Of is the blood test only indicative of ms? Anyways i support the idea.://www.examiner.co.uk/news/west-yorkshire-news/huddersfield-centre-major-breakthrough-detecting-14046936
Wow, Barts MS team I would be interested to know your thoughts on this.
I dont think this is a Safe approach. Natalizumab has a rebound effect after u stop it, and probably milder cases woudnt have a relapse while waiting three months for their dmd, but could have It with a rebound effect when stopping the natalizumab. This approach would also make a lot of patients remain on this drug, which, in my opinion, is not worth the Risk of PML. I do believe tough that we should promote induction therapy from the very beggining as the new normal, and then keep treating with whatever u want if activity keeps hitting.
I rebounded after stopping tecfidera. After 2 weeks I started tripping, fatigue. Yet up to that point my ms was mild. Also once you take something like alemtuzumab you change the balance of your immune system for good. Also any treatment after will be much more effective. However what happens ms is the wrong diagnosis? Given mri, spinal results are back within a week. I can't see if this type escalation has any benefit I was on my dmd from diagnosis after 1.5 months.
via appropriate switching you avoid rebound
What about the therapeutic lag? Fingolimod 2 months. Tecfidera 5 months. Apart from b therapies.
I can't resist a business anecdoteFrom Sep 27,1991 to Dec 15,2017 (26 years)Shares of Biogen went from 3.08$ to 327.94$ a 10546,37% gainObrigado
Did you get in early on Bitcoin, Luis? 😉
The concept seems interesting but what do you make of some the seminal works on natalizumab in MShttp://n.neurology.org/content/53/3/466.long“The number of baseline-enhancing lesions (i.e., lesions that enhanced on the baseline scan) that continued to enhance 4 weeks following the first treatment was not significantly different between the two groups.”Yes NTZ will prevent the formation of new lesions but the research above indicates that for those baseline acute active lesions NTZ is of little help. ProfG what are your thoughts on this?