As requested my talk from Cleveland!
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11 hours ago
The meeting went well and the preliminary results of the disease-activity free (DAF) survey were very helpful to illustrate the point that concept of disease-activity free (DAF) status has yet to diffuse into clinical practice.
20 Sep 2012
I am about to travel to the Cleveland Clinic, in Ohio, to attend a meeting on “Freedom from MS Disease Activity”; a subject that is very close to my heart. This concept is well advanced in the fields of oncology, rheumatology and …
29 Mar 2011
Disease activity-free status: the new gold standard? Could we use disease-activity free status to determine the effectiveness of new MS disease-modifying therapies? It may make it easier to do head-to-head studies.
I enjoyed the lecture. I'm slightly concerned that you might be waning with regard to early aggressive treatment (you didn't seem too convinced that it would impact on secondary progression). Hoeever, it sort of misses the point. I've had two doses of Alemuzumab and am relapse free for the 5 years (first infusion). I'm also stable – had improvement in the first year, but now stable. No having relapses for 5 years is a massive bonus – even if Alemtuzumab can't stop me from evenually becoming SPMS, being relapse free / no progression was worth the risk. So DAF might not last forever, but if it lasts 3,4,5 years it's a big plus (to someone having disabling relapses). If you've got a spare weekend, I could do with a little neuro-protective pill (my back-up).
Prof G – I thought you were strongly of the opinion that early aggressive was likely to delay/prevent/reduce severity of SPMS? I'm taking Alemtuzumab on the hope that is true – is it still your view that this is the case?
Yes, it is still the case. However, we can't be sure this strategy will work until we have had 15-20 years of follow-up. Fingers crossed. If we wrong we need to have a plan B; plan B is the Charcot Project.
Can individuals donate to the Charcot project? If so where/how?One other question – do we have any idea why some RRMSer (apparently c. 50%?) never progress to SPMS and some do? Is it linked to the severity of the RRMS phase?
In the pre-DMT era ~80% of MSers with relapse onset disease were progressive by 20 years. These figures are derived from hospital populations so those studies in the community will give lower levels. Why do some MSers not develop SPMS? I don't know why, but in the DMT era it may have something to do with DMTs.
One other question:Good question I do not know the answer, it would be good to know.
With regard Charcot project funding, you will need to speak to Prof G.we always need funds to keep doing and the more you have the more you can do. The Prof Gs may give some more news on the Charcot Project soon.
Very interesting lectureRe How is alemtuzumab considered so effective if DAF is only 39%: I couldn't understand the explanation. So what if it's an induction therapy? Will the DAF% go up after re-treatment?About Induction therapy the slide says "Absence of DAF status indicates a time to retreat": But couldn't it also mean non-response?The DAF status percentages are very low for BG12 too
You need to know that if you are to have a relapse, or a new MRI lesion, in the next 6-8 weeks before starting a DMT the DMT won't prevent that disease activity. The way DAF is done is it compares your scan at 2-years with the baseline scan. Therefore the new lesions could have come on in the 8 weeks before the DMTs work. Which is why we need to rebaseline the measure after the drug is fully active. With some drugs, including alemtuzumab, this period may be longer. So I would not put too much weight on this measure at the moment. This is particularly important for drugs that take time to become effective. I suspect that when you look at the number of MSers DAF at 2 years compared to the 1 year MRI the figures will be much higher.
When you say disease progression-free, do you mean that I think I'm not progressing or that my neuro thinks I'm not progressing or that the EDSS thinks I'm not progressing? It seems to me like there is a disconnect between progression on the EDSS and what feels like progression to me. When I was in a trial, I thought I was continuing to get worse and it seemed that way to my husband, too. However, my EDSS cycled erratically in a 0.5 point range (3-3.5) so I think as far as the trial was concerned, I wasn't progressing.
"there is a disconnect between progression on the EDSS and what feels like progression to me"This a problem with the EDSS (a) It is a subjective scale and (b) it is not linear, it only changes in steps (c) It on measures mobilit and there is alot more to Ms than that
V interesting lecture, thanks. Should I be hastling my doctor to do MRI scans more regularly in order to see if I am progressing whilst on a DMD? I get the EDSS done every 12 months but nothing else. This seems to definately suggest a regular MRI should be routine, including a baseline after the drug is thought to start being effective?It seems MRI's are not done routinely, only if I get new symptoms, using an MRI to rule out other causes…
I was particularly interested in your discussion of the accepted dogma and its pathways. Do you think that use of an anti retroviral in early stage disease together with a drug that stops the inflammatory response, could do away with the need for neuroprotective agents?
Re: "Do you think that use of an anti retroviral in early stage disease together with a drug that stops the inflammatory response, could do away with the need for neuroprotective agents?"This is a hypothesis worth testing; this is why we launched the Charcot project.
Re: "When you say disease progression-free, do you mean that I think I'm not progressing or that my neuro thinks I'm not progressing or that the EDSS thinks I'm not progressing? It seems to me like there is a disconnect between progression on the EDSS and what feels like progression to me. When I was in a trial, I thought I was continuing to get worse and it seemed that way to my husband, too. However, my EDSS cycled erratically in a 0.5 point range (3-3.5) so I think as far as the trial was concerned, I wasn't progressing."You highlight a problem with the EDSS it is not very reliable. We also had a lot of discussion about including a patient-related or MSer-related outcome measure but could not be sure which was relevant at this stage. Don't worry the DAF definition will change with time to include better outcome measures.
"Why do some MSers not develop SPMS? I don't know why, but in the DMT era it may have something to do with DMTs."Is there a relationship between 'severity' (however defined) of RRMS phase and likelihood of developing SPMS (which is a subtly distinct question to the r'ship between number of early relapses and time to disability)? If so, that would tend to support the role of inflammation as causitive of eventual progression (and therefore early, aggressive treatment for RRMS) but if not, that would possibly undermine the hypothesis?