ECTRIMS Highlights 2012

In response to a request by one of the readers the following is a list of my ECTRIMS highlights or insights for 2012:

1. Simvastatin 80mg per day reduced brain atrophy and delay disease progression in MSers with SPMS. Where to from here? Dr Chataway will have to find a way of getting funding to do two large phase 3 clinical trials to get the drug licensed for progressive MS. As simvastatin is off-patent this will be almost impossible. The trials required will cost upward of $100M (one commentator said to me close to $500M). This is why we need drugs that have a suitably long patent life so that industry can get involved. For those of you attacking Pharma please remember that at the present time they are the only ones with deep enough pockets and the willingness to take the risks of failing. Big Pharma is simply the only show in town when it comes to taking innovations from the bench to the beside. If you disagree please let me know how; we have a list of at least 10 ideas that need translating.

Chataway, et al. The MS-STAT trial: high dose simvastatin demonstrates neuroprotection without immune-modulation in secondary progressive multiple sclerosis (SPMS) – a phase II trial.

2. CUPID study confirms what we already know that the EDSS is a very poor outcome measure for monitoring progressive MS. MSers with EDSS scores of 6.0 (unilateral support) and 6.5 (bilateral support) on placebo hardly progressed in the study and resulted in the CUPID (THC vs. placebo) study being negative. When the analysis was limited to Msers with an EDSS < 6.0 it was positive implying that THC is neuroprotective in MS. Where to next? We need to develop better outcome measure for measuring disease progression in progressive MS. Dr Jeremy Hobart highlighted this in some detail in his lecture. In short it is time to bin the EDSS and move on. Patient or MSer related outcome measures seem the most promising.

Zajicek. Cannabinoids, symptomatic or disease modifying?

3. Laquinimod has a positive impact on disease progression and brain atrophy despite a weak impact on annualised relapse rate. Similarly, Daclizumab (anti-CD25) has a positive impact on disease progression that is out of proportion to its impact on relapses. Could these two drugs be telling us what we should already know, i.e. that relapses and disability progression are not necessarily linked? These two drugs need further work; finding out about how these drugs work will teach us a lot about progressive MS.

Comi et al. Oral laquinimod in patients with relapsing-remitting multiple sclerosis: clinical effects at 36 months in the open-label extension phase of the ALLEGRO study.

Comi et al. Laquinimod: a new MS therapy with evidence for CNS direct effect.

4. The announcement that a company in Switzerland is developing a treatment that target human endogenous retrovirus (HERV). This is in line with our thinking and would fit under the Charcot Project umbrella. Please watch this space. 

Perron et al. Novel humanised antibody therapy in multiple sclerosis targeting immunopathogenic protein from endogenous retroviral element while preserving host’s immune system. 

Curtin et al. Safety and pharmacokinetics of GNbAC1, a humanised monoclonal antibody against the multiple sclerosis retrovirus envelope protein.

5. Low vitamin D levels predict conversion from CIS to MS, i.e. the second attack. This has implications for clinical practice; we therefore make sure MSers and their families are vitamin D replete all year round. What do we do in clinical trials? Do we measure baseline levels and supplement? Is it ethical to leave MSers in trials with low vitamin D levels? What will vD supplementation do to event rates in trials? The latter will have implications for clinical trials. 

Bjørnevik et al. An age at exposure effect in the association between sun exposure and the risk of MS in Norway and Italy. The EnvIMS study. Ascherio et al. Serum 25-hydroxyvitamin D concentrations among patients in BENEFIT predicts conversion to multiple sclerosis, MRI lesions, and brain volume loss.

6. Alemtuzumab and Daclizumab increase the likelihood of MSers being MS disease activity free (DAF). This is a bit of a hobby horse; I am trying to promote DAF as a treatment target in MS. This was the subject of a recent meeting at the Cleveland clinic and has been commented in detail on this blog. Please ask your neurologist if you are DAF. 

Havrdova et al. The effect of daclizumab HYP on sustained disability progression in the SELECT trial. Giovannoni et al. Increase in proportion of patients free from disease activity following 1 year of treatment with daclizumab high-yield process in relapsing-remitting multiple sclerosis: results from the SELECT study.

Giovannoni et al. Primary results of the SELECTION trial of daclizumab HYP in relapsing multiple sclerosis. Giovannoni et al. Disability improvement with alemtuzumab vs. interferon-beta-1a in relapsing-remitting multiple sclerosis patients who relapsed on prior therapy (CARE-MS II).

7. Treatment of MSers with SPMS or PPMS with natalizumab reduced markers of inflammation and axonal damage in the spinal fluid. However, it did not normalise the levels of neurofilament implying that despite suppressing inflammation in progressive MS we need to find treatments that suppresses ongoing neuroaxonal damage; by doing this we will hopefully slow down progressive MS or hopefully stop continued progression all together. 

Romme Christensen et al. Natalizumab treatment of progressive multiple sclerosis reduces inflammation and tissue damage - results of a phase 2A proof-of-concept study.

8. Several talks confirmed what I already knew that CCSVI does not exist as a clinical entity and that the treatments being offered are dangerous and associated with significant morbidity. It makes you question the ethics of ongoing studies and whether or not governments should take action.

Comi et al. Chronic Cerebro-Spinal Venous Insufficiency (CCSVI) and global venous haemodynamics in multiple sclerosis: the CoSMo study.

Ghezzi et al. Endovascular treatment of CCSVI in patients with multiple sclerosis: clinical outcome of an Italian cohort of 462 cases.

The following are the slides from my ECTRIMS talk minus the slides I cannot show at the request of the investigators. The ECTRIMS committee will be making a recording of this talk available online in the near future.

"Overall the meeting was good; numerous meetings and networking. Some new collaborations and ideas. Very little socialising and very little champagne. I don't recall when last I have felt so tired. I also felt proud of the team; we had a good showing and some of the work we presented is cutting-edge. 

"At a personal level the feedback from my presentations was very positive with a lot of requests for my slides."

Labels: ,