Friday, 30 November 2012

Hit hard and early!

The slides from my talk in Marbella; you can download them from my slideshare site! 

"The main messages in the talk are:

1. We must adopt treatment practices from oncology (NEDD) and rheumatology (TTT) to render MSers DAF (disease-activity free). 

2. We need to formulate a definition of what a cure in MS will look like and work towards this aim.

3. We must not assume that anti-inflammatory therapies don't work in progressive MS; we may slow down the rate of progression. This is what happens with mitoxantrone.

4. Treat as early as possible; delaying treatment has long-term consequences for MSers, for example increased mortality.

5. Despite what the critics say 1st-line treatments do have an impact on long-term outcomes, albeit it moderate.

6. You can't compare MSers who are on treatment with MSers who are not on treatment; selection bias makes it impossible. MSers on treatment are more likely to have active disease and less likely to have benign disease. In comparison, those not on treatment are more likely to have benign disease and less likely to have active disease; the latter is why they elected not to go onto DMTs in the first place.

7. We don't put MSers on treatment and leave them on treatment; we now monitor for response or non-response and switch; sideways between classes or escalate to more efficacious drugs depending on the level of disease activity.

8. Non-response to DMTs is monitored using clinical (relapses & disease progression), MRI (new and enlarging T2 lesions and Gd-enhancing lesions) and with biomarkers (neutralising antibodies). 

9. Clinical and MRI activity on interferon-beta, and by inference glatiramer acetate, does not mean the same as activity in natural history studies off DMTs (slide 23 & 25). In natural history studies relapses don't predict disease progression, except in the first 2 years after disease onset. In comparison relapses on DMTs are a harbinger of progression. Therefore if you are on interferon-beta and glatiramer acetate and are having ongoing relapses and MRI activity you should discuss with your neurologist about switching treatment.

10. Disease progression be gets disease progression.

11. Confirmed disease progression in clinical trials is typically driven by relapses. I personally ignore disease progression data that is not matched by a meaningful change in the mean or median EDSS scores across the study. This is an artefact of how we use survival analysis on the EDSS. To illustrate this point I compare data from interferon-beta-1b and alemtuzumab trials.

12. The new target in MS treatment is disease-activity-free status, i.e. treat-to-target (TTT) or treat so that there is no evidence of detectable disease activity (NEDDA).

13. Whilst we wait for long-term data to come in from the alemtuzumab extension study let MSers have the option of going onto treatment in the hope that their disease will flat-line, i.e. remain disease activity free for a long period of time possibly permanently (cure). They also need to know this is an experiment and that they may comeback with SPMS in 10 to 20 years time. In the interim we need to develop treatments that delay or prevent the post-autoimmune inflammatory neurodegeneration that occurs in MS; in short neuroprotective treatments. This is why we need MSers to volunteer for neuroprotection studies. 

14. Who should decide on early aggressive treatment and what risks are they willing to take? 

15. Unfortunately, the decision regarding aggressive early treatment may ultimately be made by regulators who license these treatments or the payers who pay for these treatments. If the regulators think they are too aggressive they will be given a 2nd or 3rd license with a very narrow indication. In other words only a small number of MSers will be eligible for treatment  If they are too expensive then the payers may restrict access to these drugs; it is clear that we are entering a price sensitive era of drug accessibility."

CoI: multiple (slide 2)


  1. Thank you Prof G for putting the slides on so soon! Very good summary also. Wish everyone at the conference would be so enlightened.

  2. Many thanks - excellent summary. Can't believe they'll be any troubkle getting volunteers for neuro-protective trials! Where do we sign up?

  3. Prof. G, I saw in the Marbella conference agenda that the second part of the conference was dealing with the connection between gut flora and MS. Would it be possible to publish the slides for this part of the conference as well? Thanks

  4. It is is unusual for people to give slides, especialy if it is not published work.

  5. That's what I imagined. Just trying ;-)


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