Can ProfK join the Dots?

C

When we were children we used to get Dot to Dot books where you would join the dots to make a picture. If you just have dots you don’t really have a clue what it is you are drawing

Add a few lines to give a context and a more complete picture and it is alot easier to see what is going on, when you join the dots.

So ProfK will be getting a book for Christmas so that he learns to tell his friends on the benefits of getting the whole story at once. Because if you have a few lines at the same time you have the dots, it is a lot easier to see what is going on and if you dont get them at the same time you have forgotten all about what went before.

Today we get a book of dots

de Stefano N, Barkhof F, Montalban X, Achiron A, Derfuss T, Chan A, Hodgkinson S, Prat A, Leocani L, Schmierer K, Sellebjerg F, Vermersch P, Wiendl H, Keller B, Roy S; MAGNIFY-MS Study Group. Early Reduction of MRI Activity During 6 Months of Treatment With Cladribine Tablets for Highly Active Relapsing Multiple Sclerosis: MAGNIFY-MS. Neurol Neuroimmunol Neuroinflamm. 2022 Jun 14;9(4):e1187

Background and objectives:  This study (MAGNIFY-MS) evaluates the onset of action of cladribine tablets by observing changes in combined unique active (CUA) MRI lesion counts during the first 6 months of treatment in patients with highly active relapsing MS.

Methods: MRI was performed at screening, baseline, and at months 1, 2, 3, and 6 after initiating treatment with cladribine tablets 3.5 mg/kg.

Results: After treatment initiation, significant reductions in mean….lesion counts were observed from month 1 onward compared with the baseline period….all p < 0.0001). Mean T1 Gd+ lesion counts were decreased from month 2 onward compared with baseline

Discussion: Findings suggest an early onset of action for cladribine tablets, with an increasing reduction in active MRI lesions over time.

So join the dots and I think you get: cladribine works within one month of treatment

I suspect we will get another book of dots, which has no lines, but lots of dots. This has already been presented and this is the effect on cladribine on immune cell subsets.

Characterization of Peripheral Immune Cell Dynamics and Repopulation Patterns in the First 12 Months of Cladribine Tablets Treatment: MAGNIFY-MS Study H. Wiendl, K. Schmierer, S. Hodgkinson, T. Derfuss, A. Chan, F. Sellebjerg, A. Achiron, X. Montalban, A. Prat, N. De Stefano, F. Barkhof, L. Leocani, P. Vermersch, A. Chudecka, S. Roy, U. Boschert. ECTRIMS 2021

In that study we will have the effect of cladribine on T cells, CD4 T cells, CD8 T cells, natural killer cells, naive and memory B cells, antibody producing B cells

T cells are down but not much at 1 month and takes 3 months for nadir
B cells are all over the place some up others down(red is lowest point)

So this dot-to-dot book will be be a confusing and the story line is everything is in a network, it is all lovely and we have no idea what is going on, so we can do more work on NK cells, Th17, T regs, rather than focus our attention on something important etc.

However, if you join the the dots and you are told where to look and they are all in one place, you may get a story

Im sure ProfK can join the dots but it is not the pharma way to speculate and make suggestions….in case you are wrong or put thoughts in peoples heads:-(

COI Multiple

Disclaimer: This is the view of the author and no one else

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MouseDoctor

3 comments

  • Why is it theorized that Mavenclad does not affect monocytes? Since that wasn’t my experience – mine were slashed by 90% by end week 5, and I felt amazing temporarily.

    Since those with MS have well established gut microbiome issues, I’m beginning to wonder at the wisdom of oral dosing at all. It seems to me that meds could have a whole range of effectiveness dependent on how they are metabolized, which may not depend on weight but more on how healthy the patient’s gut and metabolic capacity is.

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