ArchiveFebruary 2022

Treat Early and Effectively

Some people make the case that there was a difference between T and B cell depleting agents and B cell depleting agents in stopping brain volume loss. This was based on the normalization (~0.2% per year) of brain volume loss in the alemtuzumab trials compared to two to three times more loss in people treated with ocrelizumab (OPERA) and Cladribine based on the phase III (CLARITY) cladribine...

Why do pharma stay clear of infection control ?Lessons and a warning from #MSCOVID19

You want a treatment against EBV and we desperately need new anti-biotics, but as soon as we can make one, the bacteria or virus can mutate to get resistance so that the drug becomes useless. This is true for SARS-CoV-2 and COVID-19. and is happening now We are feeling better because we have vaccines and anti-virals. These antivirals offer some comfort for vulnerable people should they catch SARS...

Progressive MS. How do we measure it? If you can’t measure it, how you know you’ve stopped it.

Alemtuzumab was tested in progressive MS and peple got worse and in relapsing MS people got better . This supported the view of a two stage disease process whereby relapsing MS was driven by the immune sysytem entering te CNS and progressive MS was driven by something else, that was not responsive to drugs that treated relapsing MS. So there was no hope for these drugs in, or options for...

Mass Cytometry finds B memory cells in MS spinal fluid

Flow cytometry occurs when cells are put through a “machine that goes ping” in fact it is a machine that makes cells pass through a laser and the scatter of the laser light is detected and converted into an image. The cells can be labeled with antibodies. It is one colour per antibody. Historically you would do one or two colours but the latest machines can pick up about 15-20 colours...

Predicting Low lymphocytes on dimethyl fumarate

The week NDG reported on dimethyl fumarate-induced lymphopenia Low lymphocyte counts on Tecfidera in MS So it is rather apt that we report another paper that has just surfaced Diebold M, Galli E, Kopf A, Sanderson N, Callegari I, Ingelfinger F, Núñez NG, Benkert P, Kappos L, Kuhle J, Becher B, Claassen M, Derfuss T. Immunological predictors of dimethyl fumarate-induced lymphopenia. Ann Neurol...

HSCT verses cyclophophamide for progression is no better.

Cyclophophamide is an anti-cancer drug that is not approved for MS but is used sometimes off-label. This inhibits relapses, as shown in this paper, but not quite as good as abalative HSCT stem cell therapy (This is where you get rid of the immune cells and replace the immune response using bone marrow stem cells). This inhibits relapses well, but with regard to progression they are as good or as...

Low lymphocyte counts on Tecfidera in MS

The degree of efficacy of MS drugs equates to the degree of immunosuppression. The latter is not the result of anything convoluted, but simply due to a depletion in lymphocyte counts (also called treatment related lymphopenia). Even drugs that proport not to be immunosuppressive (fingolimod and natalizumab) are immunosuppressive, but in a compartmentalized fashion. This explains the risk of...

Understanding cladribine

Recently it has been sugested that Paxlovid (COVID-19 anti-viral) and Cladribine shouldn’t mix. The question is why? This is because cladribine does not influence the cytochrome P450 degradation enzymes which are thought to increase the levels of some drugs if given with paxlovid. It seems the answer may be because it is a substrate for the Breast Cancer Resistance Protein also known as...

The case for extended interval dosing and over-dosing of CD20 depleting antibodies.

Someone said that my last long-post was not an “Easy read”. I suggested that in the Post-G era, I could’nt be bothered with ProfG-invented categories after all, what is “Thought-4-the-day” and “clinicspeak”? However, if you feel it helps ,I will continue to report the reading level from easy to super scientific Clinical trials are important human...

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