My initial highlights from ECTRIMS 2022 in Amsterdam. It is all about flipping the pyramid and going beyond inflammatory disease activity and focusing on smouldering MS.
I am being lazy here so pls excuse the next question: are there any BTKi Ph3 trials ongoing with SPMS patients currently? IF yes, when are we expecting results?
I wanted to ask your opinion on RIS and the study you highlighted (if you have time); do you think children of PwMS should be having periodic MRIs and consider treatment if they appear to be at high risk of developing MS? The NHS may never support looking at RIS (given the current challenges) but there are a number of centres that offer discounted/reasonably priced MRIs that may provide options for people.
In terms of drugs do you think using sub-cut cladrabine would be an option for high risk RIS, probably the only affordable (and potentially best) option? Do you think neurologists would be happy to prescribe it (or another drug) off-label?
I had no MS symptoms but following a quick succession of relapses post-menopause I discovered I have probably had MS for years and now, with a moderate lesion load, I am not sure where it will lead in the future. I don't want my children to be in this position if it can be avoided. What would you do if you were in my position?
I found the Tysabri vs aHSCT results very interesting especially since there are some really prominent voices beating the aHSCT drum so loud that this shows it isn't a magical fix we all want it to be. Also highlighted to me that Tysabri is a very effective treatment option
I would've liked to see more actual announcements on EBV treatments and trials starting
In this update you say 'It is a great pity that when Biogen did the ASCEND trial of natalizumab in SPMS they didn’t extend the trial to 3 years in duration. If they did, we would certainly have natalizumab as a treatment option for SPMS.'
When is someone going to do a 3 year trial to prove the nataliziumab does slow down progression of advanced MS. I suppose the real question is the percentage reduction of disability.
Pre-teens (who are Caucasian and NOT dark-skinned) whose vit D levels are supra-therapeutic may ward off MS and this was published in JAMA 2006 (K Munger et al.) See below,
Among whites (148 cases, 296 controls), the risk of multiple sclerosis significantly decreased with increasing levels of 25-hydroxyvitamin D (odds ratio [OR] for a 50-nmol/L increase in 25-hydroxyvitamin D, 0.59; 95% confidence interval, 0.36-0.97). In categorical analyses using the lowest quintile (<63.3 nmol/L) as the reference, the ORs for each subsequent quintile were 0.57, 0.57, 0.74, and 0.38 (P = .02 for trend across quintiles). Only the OR for the highest quintile, corresponding to 25-hydroxyvitamin D levels higher than 99.1 nmol/L, was significantly different from 1.00 (OR, 0.38; 95% confidence interval, 0.19-0.75; P = .006). The inverse relation with multiple sclerosis risk was particularly strong for 25-hydroxyvitamin D levels measured before age 20 years. Among blacks and Hispanics (109 cases, 218 controls), who had lower 25-hydroxyvitamin D levels than whites, no significant associations between vitamin D and multiple sclerosis risk were found.
One other question i have on BTKs - do they all work the same??
Eg like the class of B cell depleters which mostly work the same way, do the BTKs all "work" in the same way with slight differences or is each method different for each pharma drug.
Thanks for sharing Prof G. Off topic question, but I'm interested to know if you have any thoughts on fully treated cladribine patients starting a family.. Would these patients benefit from considering a DMT in the postpartum period as a safeguard against relapse?
Cannot agree w you regarding RIS. There is no such thing as RIS since DIT criteria were not pursued in the original 2009 publication in Neurology. Here goes........Neurology 2009
The cohort consisted of 41 female and 3 male subjects (median age = 38.5, range: 16.2-67.1). Clinical evaluations were performed in 44 patients at the time of initial imaging; longitudinal clinical follow-up occurred for 30 patients, and longitudinal MRI data were acquired for 41 patients. Neurologic examination at the time of the initial MRI scans was normal in nearly all cases. While radiologic progression was identified in 59% of cases, only 10 patients converted to either clinically isolated syndrome or definite MS. The presence of contrast-enhancing lesions on the initial MRI was predictive of dissemination in time on repeat imaging of the brain (hazard ratio [HR] = 3.4, 95% confidence interval [1.3, 8.7], p = 0.01).
Lumbar punctures were performed in 27 of 44 patients and CSF profiles (evaluated at different laboratories) were suggestive of MS in 67% (18/27) of these cases (IgG index 0.7 or 2 unique oligoclonal bands not ob- served in the periphery). Of the CSF cases, 11 (61%) experienced radiologic progression and 8 (44%) developed clinical symptomatology.
Application of McDonald's criteria (2017) requires CSF studies to establish DIT criteria (if MRI data is unrevealing for DIT criteria to establish a diagnostic paradigm) and while CLINICAL criteria ALONE might do the trick, or an MRI 'negative' picture might also bring about a dx of MS, I believe that RIS is truly archaic and to 'treat' RIS (not calling it MS) muddies the already muddy waters. RIS must go.
Before I comment on the RIS, story, Gavin, please take a moment to read how the term 'pre diabetes' was born or coined. It is impossible to look away; even RIS is the same. When RIS was born in 2009, it cases were not pursued religiously with CSF analysis or imaging of the cord to establish if McDonald criteria (2017) would be applicable and to be talking about an antiquated definition made in 2009 while trying to 'treat' RIS exemplifies the confused mind of an MS clinician, if you ask me. Either a person has MS or not. The rest are all healthy, albeit with different risk profiles. Medicine is full of these 'discoveries' before disease onset.
I am being lazy here so pls excuse the next question: are there any BTKi Ph3 trials ongoing with SPMS patients currently? IF yes, when are we expecting results?
Prof G thanks so much for the update on ECTRIMS.
I wanted to ask your opinion on RIS and the study you highlighted (if you have time); do you think children of PwMS should be having periodic MRIs and consider treatment if they appear to be at high risk of developing MS? The NHS may never support looking at RIS (given the current challenges) but there are a number of centres that offer discounted/reasonably priced MRIs that may provide options for people.
In terms of drugs do you think using sub-cut cladrabine would be an option for high risk RIS, probably the only affordable (and potentially best) option? Do you think neurologists would be happy to prescribe it (or another drug) off-label?
I had no MS symptoms but following a quick succession of relapses post-menopause I discovered I have probably had MS for years and now, with a moderate lesion load, I am not sure where it will lead in the future. I don't want my children to be in this position if it can be avoided. What would you do if you were in my position?
Hi Prof G, any news on remyelination trials?
I found the Tysabri vs aHSCT results very interesting especially since there are some really prominent voices beating the aHSCT drum so loud that this shows it isn't a magical fix we all want it to be. Also highlighted to me that Tysabri is a very effective treatment option
I would've liked to see more actual announcements on EBV treatments and trials starting
BTK do look very promising
Hello,
In this update you say 'It is a great pity that when Biogen did the ASCEND trial of natalizumab in SPMS they didn’t extend the trial to 3 years in duration. If they did, we would certainly have natalizumab as a treatment option for SPMS.'
When is someone going to do a 3 year trial to prove the nataliziumab does slow down progression of advanced MS. I suppose the real question is the percentage reduction of disability.
Pre-teens (who are Caucasian and NOT dark-skinned) whose vit D levels are supra-therapeutic may ward off MS and this was published in JAMA 2006 (K Munger et al.) See below,
Among whites (148 cases, 296 controls), the risk of multiple sclerosis significantly decreased with increasing levels of 25-hydroxyvitamin D (odds ratio [OR] for a 50-nmol/L increase in 25-hydroxyvitamin D, 0.59; 95% confidence interval, 0.36-0.97). In categorical analyses using the lowest quintile (<63.3 nmol/L) as the reference, the ORs for each subsequent quintile were 0.57, 0.57, 0.74, and 0.38 (P = .02 for trend across quintiles). Only the OR for the highest quintile, corresponding to 25-hydroxyvitamin D levels higher than 99.1 nmol/L, was significantly different from 1.00 (OR, 0.38; 95% confidence interval, 0.19-0.75; P = .006). The inverse relation with multiple sclerosis risk was particularly strong for 25-hydroxyvitamin D levels measured before age 20 years. Among blacks and Hispanics (109 cases, 218 controls), who had lower 25-hydroxyvitamin D levels than whites, no significant associations between vitamin D and multiple sclerosis risk were found.
One other question i have on BTKs - do they all work the same??
Eg like the class of B cell depleters which mostly work the same way, do the BTKs all "work" in the same way with slight differences or is each method different for each pharma drug.
Thanks for sharing Prof G. Off topic question, but I'm interested to know if you have any thoughts on fully treated cladribine patients starting a family.. Would these patients benefit from considering a DMT in the postpartum period as a safeguard against relapse?
Cannot agree w you regarding RIS. There is no such thing as RIS since DIT criteria were not pursued in the original 2009 publication in Neurology. Here goes........Neurology 2009
The cohort consisted of 41 female and 3 male subjects (median age = 38.5, range: 16.2-67.1). Clinical evaluations were performed in 44 patients at the time of initial imaging; longitudinal clinical follow-up occurred for 30 patients, and longitudinal MRI data were acquired for 41 patients. Neurologic examination at the time of the initial MRI scans was normal in nearly all cases. While radiologic progression was identified in 59% of cases, only 10 patients converted to either clinically isolated syndrome or definite MS. The presence of contrast-enhancing lesions on the initial MRI was predictive of dissemination in time on repeat imaging of the brain (hazard ratio [HR] = 3.4, 95% confidence interval [1.3, 8.7], p = 0.01).
Lumbar punctures were performed in 27 of 44 patients and CSF profiles (evaluated at different laboratories) were suggestive of MS in 67% (18/27) of these cases (IgG index 0.7 or 2 unique oligoclonal bands not ob- served in the periphery). Of the CSF cases, 11 (61%) experienced radiologic progression and 8 (44%) developed clinical symptomatology.
Application of McDonald's criteria (2017) requires CSF studies to establish DIT criteria (if MRI data is unrevealing for DIT criteria to establish a diagnostic paradigm) and while CLINICAL criteria ALONE might do the trick, or an MRI 'negative' picture might also bring about a dx of MS, I believe that RIS is truly archaic and to 'treat' RIS (not calling it MS) muddies the already muddy waters. RIS must go.
Jagannadha (Jay) Avasarala.
Before I comment on the RIS, story, Gavin, please take a moment to read how the term 'pre diabetes' was born or coined. It is impossible to look away; even RIS is the same. When RIS was born in 2009, it cases were not pursued religiously with CSF analysis or imaging of the cord to establish if McDonald criteria (2017) would be applicable and to be talking about an antiquated definition made in 2009 while trying to 'treat' RIS exemplifies the confused mind of an MS clinician, if you ask me. Either a person has MS or not. The rest are all healthy, albeit with different risk profiles. Medicine is full of these 'discoveries' before disease onset.
Science, 2019
https://www.science.org/content/article/war-prediabetes-could-be-boon-pharma-it-good-medicine#.Y2OpWMXg4Xo.mailto
I am sure you will love this article.
Jagannadha (Jay) Avasarala