As a bit a fatty myself, it evident that not every thing fits and this may be the same for drugs, because they are typically not prescribed based on size and is just a fixed does so if you weigh 50Kg you are going to get twice as much drug as someone who is 100kg and therefore it may not work as well. This may be the case for ocrelizumab which is given at a dose of 600mg every 6 months and there is some suggestion that if you are of a high body mass index you may not deplete B cells as well as people of a low body mass index (and has been repeated e.g. Ellwardt et al. 2018) and whilst it does ..read more

CAR-T initially developed as treatment option in cancer, but is now set to enter the MS domain to target autoreactive immune cells. This type of therapy is a world apart from our usual immunotherapies available in MS and require experienced neuroimmunologists to manage their unique side effects. Time and again I have seen comments on when will there be a cure for MS, researchers are not doing enough, it’s the same old drugs etc. If you’re willing to seek it, you will find it. But, it doesn’t come without risks. In the round up of ‘Year(s) in Review’ at the AAN including gene replacement therap ..read more

Yesterday we must have been on a fishing trip and no quicker than I posted on extended interval dosing https://multiple-sclerosis-research.org/2024/04/overdosing-anti-cd20-the-other-guy-says-i-told-you-so/ we had hooked a comment. So there you have it Faster that a speeding bullet Prof Avasarala will say that they were the first to say that we are overdosing with anti-CD20….The National Institute of Health Research must have listened….as they have put out a call (ssee below). Comment JAGANNADHA AVASARALAvApril 21, 2024 at 10:57 am “That other guy is me. I am the Director of the MS Clinic at th ..read more

The last time I talked about standard 6 monthly dosing of anti-CD20 infusions being more than the biology suggested based on our 2017 paper….someone wrote within about 5 minutes to say “I said this before you”…So I won’t say I told you so. But the biology that we highlighted is further supported, so disease remains low in people with an extended interval dose. Can the biology explain it works for so long…if the memory B cell idea has legs it can. In some cases in our cladribine studies we can that memory B cells are still depleted over 8-10 years…so it they don’t repopulate then disease isn’t ..read more

This poster is about a new anti-CD20 depleter and compares itself with teriflunomide. Yep its another anti-CD20 depleting antibody and yep it works to inhibit relapse. Here they look at progression an it says of you start less than 3 years after diagnosis your disability status score (0-10) improves by about 0.2 but after 3 years by only 0.1 but stays about the same with teriflunomide over about 2 years. But as these are treatment naive people why is it taking over 3 years to get treated. Robertson E et al. Earlier Initiation of Ublituximab Treatment Is Associated with Improved Disability Outc ..read more

This work is presented at AAN2024 and is part of a BartsMS and chumbs trilogy. A few years ago we made the case that highly-effective disease modifying drugs targeted memory B cells and suggested that rather than being a T (and B) cell depleting agent, it was going to be a B (and T cell) depleting agent. We showed (click to see) this in our cohort of people who had been taking subcutaneous cladribine and this was replicated and extended in a company funded study with oral cladribine who took bloods every 1, 2, 3, 6, and 12 months (click here to see) and 15, 18, 24 (on the way, but Click here t ..read more

This week we have the American Academy of Neurology. In terms of what’s round the corner…there is quite a number of presentations on ozanimod which is a sphingosine-1-phosphate receptor modulator that inhibits lymphocyte migration due to activity on the S1P1 receptor and hopefully supports remyelination due to activity at S1P5 receptor. This is available already in the USA, but at present it is not generally available within the whole of the United Kingdom. Notably it has not been NICEd and I do not think the company was bothered with it being NICEd as the returns were not considered to be wor ..read more

Ocrelizumab 10 years on 10 years of anti-CD20 and it looks good for 75% of people in not developing progression over 48 weeks and this was about 20% better if you started treatment earlier rather than later Hauser et al. 10 Years of Ocrelizumab Treatment in Multiple Sclerosis: Long-term Efficacy and Safety Clinical Trial Data S31.005   Objective:To assess the long-term efficacy and safety of ocrelizumab (OCR) in patients with relapsing and primary progressive multiple sclerosis (pwRMS/pwPPMS). Background:OCR is a highly effective therapy approved for treatment of RMS and PPMS. Unders ..read more

CD27 delivers a survival factor for cells and is a marker of memory B cells but it is also found on T cells and notably activated T cells. This molecule can be shed and measured in biological fluids and here it is examined in the spina fluid of people with MS and it correlates with inflammation, The more T cells the more CD27 is released. Here they link this to the amount of T cell activity within the CNS. Maybe a new marker that can be monitored. However, it won’t be any use to measure in the blood as the CD27 can be coming from anywhere Objective: Soluble CD27 is a promising cerebrospin ..read more

As you may know the United Kingdom voted to leave the European Union and as we have noticed, there have not been a lot of benefits that have emerged yet……Whilst I don’t want to get into arguments on the Pros and Cons of this however, perhaps a positive effect that has resulted from our European Divorce is that  the ability of the UK Medicines Agency to React. This is because the regulators are now, not the European Medicines Agency (making decisions across the many countries in Europe), but the MHRA (Medicines and Healthcare products Regulatory Agency) responsible for UK medicines. Howev ..read more