Yesterday, we had the online challenge from ProfG about whether MD is only interested in targeting relapse and not the real MS. I was asking about the interval between dosing with ocrelizumab and questioning how much more information we need to know that simply dosing at 6 months was more than is needed for many people. This is based on the idea that cells within the memory B cell pool are important. ProfG countered this by making the argument, (which he would as an Investigator of the double dose study), that we are actually underdosing and that by double-dosing we may be able to affect progression, the so called real MS. This was based on the suggestion that smaller (lighter) people progress less than the bigger people who don’t deplete their B cells as well.
However, before you are thinking he has started a Civil War, I have no issues with extending the the interval or doubling the dose. If you double the dose you may well get more into the brain to target progressive MS. However, it means that the antibody will be circulating for at least another month because the half life is about a month (it takes a month for half of the drug o break-down) . So you probaly could extend the interval of dosing between the dose even more. Maybe enough time for a treatment-free pregnancy, no relapses and less progression.
However, one of the readers made a comment and so the paper published below is very pertinent to the argument. So is it the dose? or is it the issue that the recipients were just fat?….So the double dose is not what will be the key but being overweight is the issue. , as being obese contributes to progression, so being smaller you will not progress. If the obesity is the issue than double-dosing may not affect this. So profG, more issues to think about. Is waist size the difference?
In the phase III studies having a BMI over 25 was associated with progression. Another question In the cladribine CLARITY trial a near double dose was used, did it make a difference in progression? or is it not relevant as cladribine gets in the brain? Are there other ways to target smouldering MS? Big questions….. but in terms of the question above, the double dose-study is being done and you will hopefully get an answer. I hope the double dose reduces progression.
Bodyweight Measures and Lifestyle Habits in Individuals with Multiple Sclerosis and Moderate to Severe Disability.Livne-Margolin M, Tokatly Latzer I, Pinhas-Hamiel O, Harari G, Achiron A.J Clin Med. 2021 May 12;10(10):2083.
Multiple sclerosis (MS) is a chronic disease marked by progressive disability and decreased mobility over time. We studied whether individuals with MS of higher disability levels will be more overweight/obese as a result of their immobility and/or recurrent steroid treatments. In a prospective study, 130 individuals with MS and significant disability were classified according to the Expanded Disability Status Scale (EDSS) score as belonging to four groups: EDSS 3.0-4.0 (n = 31, 24%), EDSS 4.5-5.5 (n = 24, 18%), EDSS = 6.0 (n = 44, 34%) and EDSS ≥ 6.5 (n = 31, 24%). Medical history, body mass index (BMI), waist circumference and the level of engagement in physical activity were obtained. The mean ± standard error age was 55.8 ± 0.5 years, disease duration 18.2 ± 1.0 years and EDSS score 5.5 ± 0.1. Disease duration, the number of steroid courses per disease duration, weight, BMI and physical activity did not differ according to the four disability groups. The mean waist circumference increased significantly with increased severity of EDSS, p = 0.03. Increased disability in individuals with MS was not correlated with disease duration, lifestyle habits or overweight/obesity. However, increased disability was associated with central obesity.
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