Tuesday, 18 March 2014

Early or late that is the question?

Delaying access to DMTs comes with a cost. Who's cost? #MSBlog #MSResearch

"I had an debate with George Ebers on Saturday about early treatment in MS. I supported early treatment and he didn't. We used Google Hangouts as the platform for the debate. Google Hangout worked but it made it very difficult not seeing and interacting with the audience. I lost the debate."

"One delegate asked me the question wouldn't I want to stratify patients up front before we offer them treatment. I am forced to stratify MSers already. He seems to forget that in the UK NICE and NHS England forced us to to stratify patients upfront. We can only offer patients DMTs if they have active relapsing MS or high-risk CIS. This is despite several data sets showing delaying therapy in CIS by as little as 18 months comes with a cost. The following picture is the cognitive data from the 5-year follow-up of the BENEFIT study (IFN-beta-1b in CIS); the difference between the CIS groups is an average delay in access to interferon-beta of 18 months. Would you like to wait 18 months? In this study you had to have CIS and 2 or more lesions on your MRI. What people seem to forget is that having a low lesion load at baseline is probably down to luck; i.e. you were lucky to present with an attack after your 2nd or 3rd lesion. Those CISers with high lesion loads have had the disease longer and have had more time to accumulate a lesions load. In other word it was their 15th, 16th or 30th lesion that causes them to present. What determines whether or not a lesion causes symptoms is where in the brain or spinal cord the lesion occurs. I therefore think that if you have CIS and a low lesion load you are lucky and it gives us a greater opportunity to prevent or reduce damage earlier. Why would we wait for you to increase your lesion load and damage to offer you treatment?"


"Please note that despite EDSS (physical disability staying stable, the PASAT separates over time between CISers treated early and those treated later. The initial improvement in both groups is due to practice effects; simply doing the PASAT improves your cognitive functioning. The latter is why I always tell my patients that brain health, i.e. brain activity is good for you."

"The following are our current prescribing guidelines; I have deliberately highlighted the clinical criteria to show how restrictive  they are both in terms of starting and escalating your treatment."

The following is the current NHS prescribing policy

The starting and stopping criteria for the use of beta interferon and glatiramer acetate are based upon the criteria outlined in the Association of British Neurologists (ABN) Guidelines 2002/04. 

Beta interferon for relapsing remitting disease 

All of the following criteria must be met. The patient:  

  • has had at least 2 clinically significant relapses in previous 2 years
  • is able to walk 10m or more**  
  • is not pregnant or attempting conception  
  • is aged over 18 years  
  • has no contra-indications 

 * Neurologists may, in certain other circumstances where the evidence for efficacy is 
less secure, also consider advising treatment after discussion with the patient 
concerning the risks and benefits. For example; 

(i) Patients within 12 months of a clinically significant clinically isolated syndrome when 
MRI evidence predicts a high likelihood of recurrent episodes (i.e. development of MS). 

(ii) patients with only a single major relapse in the preceding two years, but 
combined with MRI evidence of continuing disease activity (i.e. meet the revised 
McDonald criteria for MS) 

(iii) individuals aged less than 18 with relapsing remitting MS
  
** For patients who can walk between 10 and 99 m (aided or unaided, EDSS 6.0 to 6.5), treatment with DMTs is permitted but recommended less strongly than for patients able to walk more than 100m unaided (EDSS 5.5 or less). 

Glatiramer acetate for relapsing remitting disease  

All of the following criteria must be met. The patient:  

  •  has had at least 2 clinically significant relapses in previous 2 years 
  •  is able to walk 100m or more without assistance* 
  •  is not pregnant or attempting conception  
  •  is aged over 18 years  
  •  has no contra-indications  

*without assistance means that the patient is free standing and does not require walking aids. 

Natalizumab for rapidly evolving severe (RES) relapsing-remitting MS 

All of the following criteria* must be met. The patient:  
  • has had two or more disabling relapses in the past year  
  • has one or more gadolinium-enhancing lesions on MRI or increase in T2 lesion load compared with previous MRI unless comparator MRI is unavailable or assessment of gadolinium-enhancement is unreliable as the patient is treated with steroids at around the time of scan.  
  • has had no previous disease modifying therapy OR is receiving treatment with beta interferon and does not meet the agreed stopping criteria.  
*As per NICE Technology Appraisal Guidance 127 patients with high disease activity taking beta interferon or glatiramer acetate but do not fulfil the RES criteria will not be routinely funded for natalizumab. 

Fingolimod for highly active relapsing – remitting MS 

Fingolimod is recommended for the treatment of highly active relapsing–remitting 
MS in adults, only if the following criteria are met:  
  • Patients have an unchanged or increased relapse rate or ongoing severe relapses compared with the previous year despite treatment with beta interferon*, and 
  • The manufacturer provides fingolimod with the discount agreed as part of the patient access scheme. 
"As you can see we are not allowed to treat MSers with clinically inactive MS nor are we allowed to escalate treatment unless MSers on established therapies, are relapsing, and then only after a significant period of time. Who is being hoodwinked?"

CoI: multiple

9 comments:

  1. Prof. G. This post is an eye-opener. Is it really true that people with MS lose cognitive function without becoming disabled? Do you think the newer agents will be better than interferon in protecting cognition?

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  2. Why did you lose the debate? Who decided?

    Am I right in assuming the Prof E doesn't think relapses are that important i.e. they are just a response to a neuro-degenerative process? If so, what it Prof E's approach to treating patients if he's not a fan of dmts?

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    Replies
    1. Re: "Why did you lose the debate? Who decided?"

      It was done by a vote; the audience did bot think the evidence is firm enough to support early treatment. Prof. Ebers wants more evidence regarding DMTs. He wants data showing that the treatments delay or prevent the onset of secondary progressive MS. He is retired now so not seeing MSers.

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    2. Just out of curiousity, did this voting audience have MS?

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  3. I think MSers in the UK are being mismanaged. If this happened in the US a good lawyer, with a class action legal challenge, will sort out NICE and NHS England.

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    Replies
    1. Erm, I think the US has banned alemtuzamab. So much for good attorneys.

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  4. Presumably the CISers in the BENEFIT study who benefitted were those who were responders to beta interferon. As a sizeable proportion of MSers aren't responders then a test to see if they were before starting treatment would be very useful, though I don't suppose Pharma would be interested in researching into one as they make lots of money out of non responders. It's sad that fingolimod is a second line treatment whilst nataluzimab can be first line when you consider their side effects.

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  5. Until we have markers of assessing the efficacy of a treatment, the Treaters will continue to be unsure about whether the DMTs are working for patients (long-term).

    Are you saying that number/amount of lesions from MRI can be somewhat correlated with the potential for progression.. or even give an idea of disease activity? i.e. high lesion load can definitely be associated with worse prognosis vs light lesion load?

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  6. Prof G,

    Why are we still having this debate? The first interferons came into clinical practice some 20 years ago. Campath was first trialled on MSers over 20 years ago. The first Tysabri trials must have started some 15 years ago. Yet no one can categorically state that any of these drugs has a marked effect on an MSer's future disability. A proper researcher should be getting hold of the data from these early trials etc. and finding out how the partipants are doing now (and comparing this to historical preDMT outcome data). I'm sure the debate was of interest to academics, but as a patient I want to find out if its worth continuing with my current or does it make no real difference to my outcome.

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