Sunday, 29 April 2018

AAN2018: Laquinimod joins the PPMS graveyard

I am just back from LaLa Land and the AAN2018 meeting. I am feeling exhausted, MSed-out, conferenced-out and very concerned about the future of neurology (more on this on my Medium post). 


The AAN2018 was far too long, too spread-out (the venue was cavernous with rooms that were in general too large) and too expensive (conference fees, LA hotels, restaurants, regional wines and flights). The AAN is definitely not the premier MS meeting it used to be. ECTRIMS and ACTRIMS have usurped the AAN to such a degree that there was very little new MS data presented at this meeting. My presentation on the Arpeggio results was at least novel. As promised I have uploaded it onto SlideShare for you to browse. 


In short, the Arpeggio study was negative but does shows Laquinimod has an effect on brain volume in the first 6 months and that it has anti-inflammatory effects. I suspect this is due to laquinimod's effect on glial cells, i.e. it causes them to swell.



What the Arpeggio and other recent studies question is the use of short-term brain volume changes as a marker of neuroprotection in progressive MS. Short-term changes don't necessarily mean neuronal or axonal protection; Arpeggio shows that. Therefore I would be very careful to draw any conclusions about brain volume changes without other biomarker and clinical changes going in the right direction to infer neuroprotection.

The AAN2018 will be remembered as the NFL meeting; i.e. the time when neurofilament light chain became accepted as the MS soluble biomarker of choice. Numerous presentations from clinical trial datasets have established NFL as a predictive, prognostic and treatment outcome biomarker in RRMS and possibly progressive MS. It is clear that NFL levels track most closely with inflammatory MS activity, i.e. relapses and focal MRI activity. The role of NFL as a biomarker in non-relapsing progressive MS is less certain. We will have to wait for additional data to be analysed and presented to assess its utility in progressive MS.

NFL is our equivalent to the CRP in rheumatology. 

ProfG    

23 comments:

  1. Prof G you shouldn't travel business class and you could avoid hotels (Airbnb is a cheaper option).

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    1. I believe Roche flew out DrK and several other UK neurologists business class and you had to fly economy?

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    2. You have too much at stake to add the stress of flying Economy. To keep going at your pace you should definitely be flying Business when/wherever you jet off to. It's the only way to avoid the stress on your musculo-skeletal system caused by long haul flights. I know, because I've had to start doing it because of the MS. This has cut down the number of times I can travel but it's worth it.

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    3. I can't afford business class; University policy is for us to fly economy or premium economy.

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    4. When industry is involved, and you do a job for them (rather than simply "attending" a conference), I guess nobody would object spending the 10 hours to and from LA in business class. Just as ProfG did on this occasion (oftentimes it's been vice versa) I attended a conference in Honolulu last year on a budget, i.e. economy flights (no premium) and Airbnb, including some creepy crawlies inhabiting my bed on day 1:-( The conditions & choices vary between occasions.

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  2. Any other news that is worth commenting about? How was your B cell paper received? Any news on new DMTs?

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    1. I had to leave the AAN early so didn't wait for the final session However the poster was one of the hot topics Bryan had a crowd around the poster most of the time

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    2. Some of us held out until the very end; Bryan's talk was very well received: https://twitter.com/KlausSchmierer/status/990025681810604032

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  3. Every year you come back from these conferences and moan. Yet, you'll be there again next year + ACTRIMS, ECTRIMS, Charcot Foundation..... It's pretty clear why it's difficult to get an appointment with a neurologist these days - they are usually attending an international conference or doing some paid work for pharma. And Team G blames government cuts! These international conferences are just circuses. Attendees are so worried that their profiles might be hit if they don't attend. Before moaning too much, spare a thought for those with MS who have lost their jobs and can no longer travel long distances. I would love you to take up my May challenge - keep off all social media, no attendances at international conferences, reject any offers to do more work for pharma, have one day a week having time / a meal with your family, breath. You have got caught up in this web of self-importance and forgotten your other roles - father, husband friend. You've done your bit for MS. There are lots of Young Turks who can fill the void. Enjoy life. No one went to their grave and said they the thing they would have changed in their life is to have worked more!

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  4. “Treating disease will become a smaller part of our work”. There are no treatments for neurodegenerative disease: ALS, Parkinson’s, progressive MS, etc. they are merely managed. Where is the urgency? Maybe another ice bucket challenge for ALS will placate the patients. These large, international meetings are just Pharma social gatherings. LA is the perfect venue for this wine and dine affair.

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    1. You will need to ask the American neurologists, they are the ones who are burnt out and apparently underpaid

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  5. ProfG, with automation arriving in the medical industry it's time for doctors to evaluate their roles. I've been admitted to the hospital a few times. I got to see the doctor for barely a few minutes each day. It was the nurses who actually took care of me at all times. They helped me manage my pain, helped me walk, helped me in the bathroom. No doctor would ever provide that kind of personal care. I have to drag myself to my doctors office when I am in the middle of a relapse. Maybe MS doctors should consider doing house calls to make it slightly easier for patients. There are several ways you can save the neurology profession if you think about it.

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    1. I agree. It is all about teams and not individuals. The neurologist is only a small part of that team with a shrinking role

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  6. "I am just back from LaLa Land and the AAN2018 meeting. I am feeling exhausted, MSed-out, conferenced-out "

    “The busy man is never wise and the wise man is never busy.”

    Lin Yutang

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    1. It is called jet lag; not sure if has anything to do with being busy, not busy, wise or unwise.

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  7. So much to think about...

    Looking at the slides (I have reached #6) I do not understand "T2 lesion volume" - can you help? It was good to see 9HPT at least an Exploratory Endpoint but unclear, reading on, how or when it was used.

    Is there a reason you use SlideShare, and not Google, for sharing your presentations? I find LinkedIn too predatory with my contacts and have to switch accounts before touching it

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    1. SlideShare makes it easier to share PDFs.

      T2 lesion effects are due to laquinimod's anti-inflammatory effects.

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  8. Ibudlist showed 50 % decrease in brain volume loss so is this possibly meaningless as well?

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    1. "Ibudilast showed 50 % decrease in brain volume loss so is this possibly meaningless as well?"

      If this were an isolated finding then maybe. However, the new data presented in LA suggest an 80%(!) difference in cortical grey matter volume loss, and 81%(!) difference in magnetization transfer ratio (MTR, an index of macromolecular content, largely myelin) compared to placebo. If this is all true (let's hope we don't have to wait a long time for the paper to be published) it adds credibility to the data presented at ECTRIMS last year, and I hope phase III plans are evolving at speed (a colleague attending the AAN and involved in the trial program said so).

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    2. Thanks Dr Klaus. I'm right this not just moderately effective like ocrelizumab and spinimod but highly effective. Given your percentage. If so and given its already available and proven to be safe should patients start self medicating?

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    3. It's anybody's choice what they do with the data available so far. I would not advise using it *at the very least* until the new data have been peer-reviewed and published. One caveat is there was no effect on clinical outcomes. Whilst this cannot necessarily be expected since the trial was geared towards a secondary outcome (brain volume), remember the first MS-STAT trial showed such effects (and is now in phase III).

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