Flatlining MS disease activity; what do we need to do to make it a reality? #MSBlog #MSResearch
“In the last few weeks we have been discussing the paradigm of early effective treatment as an emerging treatment strategy to suppress all disease activity before MS causes any significant damage. Why? Simply because the earlier you prevent damage the better the prognosis. The reason for this that the brain and spinal cord have reserve capacity to adapt to damage by compensating. Once one’s compensatory capacity is exhausted you enter the progressive phase of the disease. Prior to the progressive phase of the disease MSers who are compensating for damage may experience activity-dependent fatigue; in other words they fatigue earlier than normal controls when doing challenging cognitive or even physical tasks. There is a energy cost of compensation. Evidence for previous damage in MSers who are functioning normally can usually be detected with detailed cognitive assessments or using sensitive MRI outcomes for example brain atrophy.”
“Some of you are cynical about the concept of early effective treatment working. I agree that we don’t have the necessary long-term data at hand. But we do have early data suggesting this is a viable treatment strategy. The question that needs to be asked is ‘should we deny MSers today access to this treatment whilst we wait for the data to emerge supporting this treatment over the next 10-20 years?’ The following are three examples of highly effective treatments that flatline disability in the majority of MSers treated with them early in the course of their disease.”
“In the last few weeks we have been discussing the paradigm of early effective treatment as an emerging treatment strategy to suppress all disease activity before MS causes any significant damage. Why? Simply because the earlier you prevent damage the better the prognosis. The reason for this that the brain and spinal cord have reserve capacity to adapt to damage by compensating. Once one’s compensatory capacity is exhausted you enter the progressive phase of the disease. Prior to the progressive phase of the disease MSers who are compensating for damage may experience activity-dependent fatigue; in other words they fatigue earlier than normal controls when doing challenging cognitive or even physical tasks. There is a energy cost of compensation. Evidence for previous damage in MSers who are functioning normally can usually be detected with detailed cognitive assessments or using sensitive MRI outcomes for example brain atrophy.”
“Some of you are cynical about the concept of early effective treatment working. I agree that we don’t have the necessary long-term data at hand. But we do have early data suggesting this is a viable treatment strategy. The question that needs to be asked is ‘should we deny MSers today access to this treatment whilst we wait for the data to emerge supporting this treatment over the next 10-20 years?’ The following are three examples of highly effective treatments that flatline disability in the majority of MSers treated with them early in the course of their disease.”
Coles et al. Alemtuzumab more effective than interferon β-1a at 5-year follow-up of CAMMS223 clinical trial. Neurology. 2012 Apr 3;78(14):1069-78.
“Alemtuzumab, natalizumab and cladribine are all punt in the high-efficacy zone. It is clear that MSers when given access to these treatments do very well in the short-term. I am not saying that all MSers do well; there are a minority who have breakthrough disease that need to be retreated or considered for another treatment. However, the majority do well.”
“The problem we have in Europe and the UK is that the regulators don’t want us to have wider access to these treatments. They want to limit their use to a small group of highly active MSers (two disabling attacks in a 12 month period with active MRI) and to use them second line in MSers who fail the so called platform therapies. The problem with the latter is that you have to not just fail them, but fail them badly with very active disease. This strategy leaves MSers with smouldering MS in no-man’s land; i.e. active disease but without access to more effective treatments. Another worry is the introduction of several other first-line therapies. Will our payers expect MSers to cycle through all the first-line therapies before accessing the next tier of highly active treatments? This cycling is what concerns me most; spending years with smouldering MS on ineffective or partially effective therapies will result in MSers acquiring significant damage before accessing the necessary treatments.”
“Data on the newer more effective agents and my concerns about the consequences of delaying access to treatment is why I am campaigning for earlier access to these treatments and the change in treatment philosophy from ‘safe and smooth’ to ‘early highly-active’ treatments. Can we really expect MSers to wait for the outcome of an experiment that will take another 15-20 years? Why can’t they become part of that experiment? Surely MSers are capable of making their own decisions about risks and benefits? Why should regulators, payers and neurologists make these decisions for MSers?”
CoI: multiple
P.S. “Despite very good efficacy data the EMA and FDA decided not give cladribine a license. As a result of this decision the company developing cladribine have decided not to develop the drug further. Can we, the MS community, resurrect cladribine? I hope so; it is a very effective treatment.”
This should be really good news, that is, that there are effective treatments which if given early, can delay the onset of progressive disease/reduce disability in later years. I quite understand your concerns and frustrations (similar to your 'what can we learn from the HIV pandemic?' post). We need Radical Action for MS – RAMS rather than LAMBS : Let's All Moan a Bit (in the typical UK way…)
Maybe you should start an MSer led petition? As a start you should all write to your MPs. This can at least be done from the comfort of a desk. I note a lot of MSers said they were too fatigued to protest outdoors. We need an e-protesting campaign. The MS Trust, MS Society, Shift MS and any other MS charities need to get involved with the petition. Any other ideas would be much appreciated?
Your right a sustained internet petition will be a start. If we have someone out there who is internet savvy it would help alot. I have a few basic computer skills , but i'm willing to help put this petition into action.PLease let me know through my email if we can get a working party together.email jfms57@gmail.com. Jenny Ferguson
Jenny I'll get in touch later as it isn't convenient at the moment. Prof G – at your suggestion I looked at the EMA – essentially 'patient' involvement means being part of a group or organisation. Maybe with the epetition we would have the kernel of such a group. One thing, though is that there are already lots of MS related groups, which I think tends to dilute the message and isn't an efficient use of the limited time energy and other resources. Just off the top of my head, in the UK we have the MS Society, the MS trust, shift.ms, MS UK and the research one (sorryI've forgotten its name) + the MS NTC and all the therapy Centres. One benefit is that they all add up to a lot of people but aligned with disparate organisations.
Will look into it… from anon 16.00
I have never seen such data for Mitoxantrone (Novantrone, Ralenova). And I know a lot of MSers how have taken Mitox and MS came to a stop. I even know of 2 MSers who never ever had a relapse again for over 15 years.I will have my 8th infusion in 2 weeks and didn't have a relapse in the last 2 years (although I know that this could also happen if I hadn't taken any drugs).So is there data like in the above graphs availible for Mitox??Thanks
see todays post
We then get back into the minefield of 'off label' prescribing. Although alem's gone for the present, IV cladribine is possible if you have a neuro who is willing to prescribe it. As you know, MSers are often more willing to take a risk than their neuros are, and many would be willing to absolve their neuro of blame if any of the rare side effects happen.You may be on ethically soft ground, but how ethical is it not to offer these effective treatments. I'm not getting at Prof G personally, rather the whole neuro community. Perhaps we need a neuro nearing the end of his career who believes in early highly effective treatment, and doesn't care what the NHS or NICE think to prescribe them.When alem is finally approved as a 2nd, 3rd or 4th line treatment, will neuros tell new MSers that it's most effective the earlier it is used, but the only way to get it as an induction therapy would be to pay privately?I will write to my MP, but knowing how indolent he is, he'll just pass it on to the Minister for Health.
Agree with anon 12.31 above. Neuros have got to start prescribing the more effective treatments following discussion with their patients. When a patient is diagnosed the neuro should set out all treatment options, benefits and risks. Patient to decide with neuro what they want based on their appetite for risk etc. if the regulators are so prescriptive, why do we need a neuro? Can go to GP who dishes out first line therapy.
As a patient using Tysabri (Natalizumab) given as the first line of treatment following 2 relapses after being diagnosed with highly active RRMS, the question I have is how long can a patient stay on drugs like this before they start being ineffective. I have been on it for 3 years, has anyone been on it longer?. Or is it a holding strategy until something better comes along, because once you are on it there doesn't seem anywhere else to go.
This is a political solution. the parliamentary ms group should get off their bums. With ineffective e petition and one hundred thousand signatures they have tolerate it. Maybe prof g Will finish his bpa article in bari so we have a working reference.Otherwise we sill get stock answers
MD I can't understand what you meant by your last post – do you mean that despite an effective e-petition with over 100,000 signatures, the parliamentary group still tolerates the situation? Also, what is the bpa article (presume it will be mentioned nthis blog)? Thanks, sorry to add to your workload but I am psychng myself up to take action :-)!
No he means they can't ignore an e-petition with 100, 000 signatures.The government e-petition site is here. http://epetitions.direct.gov.uk/The key is to frame the right question such as "Should MS patients have the choice to be treated with highly effective disease modifying therapies as a first line therapy rather than having to wait until they fail on the currently prescribed first line therapies?".Then there has to be an effective lobbying campaign to get as many signatures as possible.
If the petition got circulated to all the UK MS sites/patient groups etc it may have a chance of getting the required number of signatures.
Or cast the question broader as this has implications bigger than just MS
All the talk so far about early tx has been in the context of… wel… early. What about those of us who were not diagnosed for years, or did not have the option of getting on DMTs early on? Do we know if there still is a benefit for starting late?I have MS for at least 10 yrs now. Took 3yrs until it was diagnosed correctly, and was not offered tax until 3yrs after that, even though it was clinically "mild". clinically and radiologically my MS has been stable for a few yrs now… is no discernable relapses and no MRI changes. fatigue and cognitive problems are my biggest complaints though. Seems these go downhill probably independent of clinical relapses, as compensation mechanisms get overwhelmed.I'm sure there are others like me who have been classed as "benign" MSers. Is there still any benefit of getting on tx? Where do we figure in this topic. I feel we are in a bit of a limbo: missed out on early tx (without going into discussion on efficacy), but no one can tell us whether it is too late for us… are we at the mercy of degeneration/progression even if we get on tx, because of damage already done.
Stopping further disease activity when ever you start will be a good thing. What is not known is progressive disease and when is the dice cast. That I do not think is definitely known.Remember with regard to treatment…it is a risk-benefit. Today profG was talking about a drug with 0.8% risk of cancer this is 1 in 125 with a 50% risk of mortality. Compare this to tysabri 1 in 94 risk of PML with 25% chance of dying.
Maybe you'll get a reply to this but we don't usually.Happy to join in a campaign: pamnewall1@mac.comCan publicise through Shropshire Disability Network too.
Thanks once some more thought is given your help will be appreciated. and a reply:-)
pamnewall1 a couple of us have made contact so I will get in touch with you, too
Prof G, please keep beating this drum in the neurology community too. If the authorities can find neurologists who don't agree with early effective treatment, it gives them a good excuse to deny it