“Does the aphorism ‘Time is Brain’ apply to MS? Yes, I think it does. When we were attempting to get alemtuzumab licensed as a firstline treatment in Europe, I used the following two case studies to illustrate what the potential price is of delaying access to a highly-active treatment; an 18 month delay and two relapses later is the difference between the two narratives (EDSS 0.0 vs. EDSS 3.5).”
“Both these patients kindly agreed to have their case studies presented and ultimately written-up. Both are out of the MS closet and have published lay summaries of their experiences (see below). I appreciate them doing so; a story, or narrative, makes the trial data relevant and come alive. The following slideshow is a precis of their case reports and tries to put their stories into a contemporary context of treating-2-target of NEDA with a choice of an induction therapy in the hope that it results in long-term remission and possibly an MS cure.”
“Why I am I rehashing this theme? Simply because I am currently looking after a patient who clearly illustrates ‘Time Matters’. This patient has highly-active RRMS and is JCV seropositive. Whilst she was waiting for her NHS alemtuzumab infusion slot she has had a devastating spinal cord relapse. If she had had her alemtuzumab the week after we had made the decision to go the induction route this relapse would probably have been prevented. She is now EDSS 7.0 with bilateral sphincter involvement. At present she requires a urinary catheter. Although she is likely to make a recovery from this attack the recovery may be incomplete. I sincerely hope she doesn’t pay the price of an NHS delay.”
“When you analyse how much time is wasted in MS care pathways you quickly realise that we, the MS community, need to change our attitude to the management of MS. This is why I am leading on a MS policy document focusing on the issues ‘time matters’ and ‘brain health’. Only after we change our management philosophy and treat MS focusing on long-term brain and spinal cord health will maximise the promised improvements in outcome that our therapies offer relapsing MSers in 2015. May be you disagree?”
McCarthy et al. Timing is everything in the treatment of multiple sclerosis. BMJ Case Rep. 2015 Apr 15;2015.
We present two similar cases of relapsing-remitting multiple sclerosis, both of whom received treatment with the monoclonal antibody alemtuzumab, but had significantly different long-term outcomes. Patient A is 12 years into his illness and was treated early in his disease course, he has no disability and continues to perform at a high level as a professional golfer. Patient B was initially started on interferon-β1a therapy and went on to have two disabling relapses on this treatment which resulted in a degree of fixed disability prior to the start of alemtuzumab. 10 years into his disease course he has moderate disability and daily symptoms of spasticity in his legs which impair his quality of life. These two contrasting cases highlight the difficult decision of when to start potent immune modulating therapies for multiple sclerosis in young adults who appear well early in their disease but have the potential to rapidly accrue irreversible disability from future relapses.
25 thoughts on “ClinicSpeak: does time matter?”
I had to wait nearly four months between having my first MRI and getting to see the neuro a second time to be told that the MS which was supposed to have been "ruled out" by the MRI was in fact "ruled in". This was despite a radiologist's report about my numerous brain and spinal lesions having been sent to the neurologist within a couple of weeks of the MRI being done. During the time between first and second appointments with the neuro things had become so bad I'd had to stop work. No – I'm not in a third world country, but our health system didn't have any "contingency" plans for dealing with things such as blatantly abnormal MRI results.So, of course time matters.
I could not agree more strongly, I lost my mother to this and my brother went from walking to bed ridden in 1 attack, no recovery. I am taking care of myself. I don't know how to politely say this as I don't want to offend people but I'll try:Those of us with RRMS need to do more to help ourselves to change the narrative and free up doctors and researchers to work on PPMS and SPMS. Why are there so many MS blogs focusing on negatives? Themes like, I am taking CRAB or no medication and am suffering through this latest issue. I have seen two of the worst possible cases, this is not something to triffle with, as I said I am taking a highly effective therapy and look forward to the future. I want others to see that the future is OK and that current treatments can change the narrative.
Three members of your immediate family have/ had MS?I wonder if the genetic factor is stronger in some family nexuses than others?
Yes, three members.
Prof G,Thanks. These real life cases really bring the issue to life. For the patient who is NEDA and EDSS 3.5 what are the treatment options? Are there any treatments on the horizon which could repair damage and reduce the EDSS score? I'm 3 and would love to reduce it to .
I realize that the policy for management of MS begins in the minds of neurologists themselves, and from what I gather it is worldwide. I speak for myself, I was diagnosed last year after the first symptoms arise. My EDSS is 1.0, I am currently treating me with Glatiramer. I have a brain injury and spinal cord in the neck, which was the one that was active and that caused me the symptoms that led me to the diagnosis … Well if I could, if I had to choose I would go for a stronger DMT, up to alemtuzumab without any problem … The problem are the thoughts of my neurologist about how to conduct the treatment, why not think "ah her illness is at the beginning but has already presented a well-symptomatic spinal cord injury. Maybe try to avoid injuries future like this we go to a more effective DMT. "… I see neuros treat cases of MS and more active, more commitment, even with DMT's less effective, the patient continues to show commitment but it seems that for fear of possible side effects neurologists are afraid to take a step further …
You've illustrated the need for early and prompt treatment… how to mobilise people to campaign…? Or do you think the need ot treat early is now being taken seriously (by the decision makers?)
Six months between first relapse and neuro appointment. One year between first relapse and MS neuro appointment. In UK.
Prof G,Couldn't agree more. So, do you think the treatment 'pyramid' should be flipped for all RRMS patients? As in treat all confirmed RRMS patients aggressively early with MABs. Seems there is no place for CRAB drugs now & possibly not even the oral DMTs. Thanks
The pyramid has immunomodulation on the bottom this could be an effective CRAB or one of the newer DMT on which you layer neuroprotection and repair. The key is that the bottom of the pyramid has to be NEDA. If the CRAB drug is not achieving NEDA, then the last B becomes P and you need to escalate some Neuros have dispensed with using the CRAB drugs.
If we're looking at NEDA-4, CRAB drugs don't address brain atrophy though right?
yep so put that into your choice scenario
Thanks MD,So the only treatments that address brain atrophy are Alemtuzumab & HSCT?
You can have highly active MS, maybe a few attacks a year and still be less than 2 EDSS (in the first few years of disease course) so is it the case that time matters or that your level of EDSS matters at the stage you take alemtuzumab? I realise that othere damage may have been caused that doesn't affect your EDSS, but I'm sure that neuro doc G said that epidemiologically you do not progress whilst your EDSS is less than 2
It is reasonable to think that starting a treatment as early as possible is a good idea. Still, taking an immuno-suppressive drug like an infusion is everything but benign. It can cause death. MS is a debilitating disease (not cool too), but it does not cause death. I am not saying that one should not take infusion, but maybe one should be cautious about their promotion.Plus, I hate to say this, but n=2 is wishful thinking and not a scientific result. She might have avoid this serious relapse – or not. Low number of cases should be also taken with precaution (a lot of it); this is especially true in MS where people can experienced a huge variety of symptoms and relapse frequency even without treatment. For instance, I and a MS friend use exact same treatment, same age but I have motor problems that she does not have.
I don't know what you mean n=2? I'm not suggesting someone is going to stay at less than 2 EDSS without treatment, or with one of the less effective DMts. What I am asking is that if they are at EDSS less than 2 when they receive alemtuzumab are they much less likely to progress no matter how long they have had the disease. As you say relapses can have very different effects- some people have 'minor' and some people have 'major' rrelapses and you can't tell beforehand what it is going to be. MS can cause death, infusions can cause death (both in a relatively small number of cases), but it's the risk;benefit ratio and what you are willing to accept to live as normal a life as possible
"Plus, I hate to say this, but n=2 is wishful thinking and not a scientific result."It's a couple of case histories for illustrative purposes (for anon 2:50 n is the number of subjects in an experiment) nothing more, nothing less. The point is that in some cases, the consequences of doing nothing and hoping for the best can be devastating.
By "n=2" I mean they study only two cases in this article like MouseDoctor said. I fully agree with you that it can be devastating to do nothing and let a disease run its course, but sometimes the cure could be worse than the disease itself "La saigné" (a stupid French idea) is a good example. BTW I also agree with you that reporting cases is a very important work of doctors and I really like your blog!
i am sure this is many more than n=2 and have seen a few peoe . There is about 40% NEDA.Whilst many people will recover from relapse some wont
XoR XoR – that MS doesn't cause death is a myth. Ask my husband – 42 years old, suffering from his 16th UTI in 2 years and almost out of antibiotics, frequent choking due to an impaired swallowing reflex, and on blood thinners for life to head off another DVT. MS does kill. We are not alone in this.
Very sorry for your husband. What I meant, and your case is illustrative of that, is that MS can have devastating consequences but is not lethal by itself. It does not directly cause death but its consequence might. It could sound like a matter of words but it is not. MS has a huge variety of forms. In the case of your husband there is no doubt a treatment even if it can be lethal might be thought of, but they are certain people (lucky ones) that have MS but not all these devastating consequences.
MS does kill; seen it happen.
I know that there is a wide difference between the severity of MS case; but I do not agree that MS does not kill. However; I think that patients should have a choice. Just like Morpheus offered the choice of a red pill or blue pill to Neo; shouldn't patients have the choice of highly effective or not? Am horrified to hear about the wait times above, this makes me very upset.