Can’t Neuros just flipping Read!

C

This is one of those posts where I bring our profession into disrepute. The neuros are gods when they do something that works and yes I am not worthy when it comes to licking the bosses boots, but eventually you have to crack. I have been reporting year after year as a stocking filler for when ProfG or some other neuros posts something of interest. Therefore I have read a lot and you see this trial come and that trial go and sadly you see this trial fail and that trial fail and I scratch my head when the neuro does another one. The idea of putting anti-CD20 into the brain has been tried and tried and if fails and fails. Now to be fair this study started in 2015 and many of the negative trials surfaced in 2016. But trials are registered but that does not stop others following in the footsteps….How many vitamin D trials have been done and how many underpowered microbiome trials are being done. I guess if you have a birght idea, someone somewhere else is having the same bright idea. This is seen in the COVID era where everyone is doing the same thing….search N95 mask and COVID-19 and you have hundreds of papers. Intrathecal (into the spinal space) has been done intraventricular anti-CD20 has been done. Bergman J et al. Fluids Barriers CNS. 2020;17(1):49. When will we see the results of cladribine…a B cell killer that can get in the brain.

No Early Effect of Intrathecal Rituximab in Progressive Multiple Sclerosis (EFFRITE Clinical Trial).Bonnan M, Ferrari S, Courtade H, Money P, Desblache P, Barroso B, Debeugny S.Mult Scler Int. 2021 Mar 8;2021:8813498. doi: 10.1155/2021/8813498. eCollection 2021

Background: The progressive phase of multiple sclerosis (MS) is characterized by an intrathecal (IT) compartmentalization of inflammation, involving B-cells within meningeal follicles, and resisting all the available immunosuppressive treatments. A new therapeutic paradigm may be to target this inflammation by injecting immunosuppressive drugs inside the central nervous system compartment.

Methods: We designed a single-center, open-label, randomized, controlled, phase II study designed to evaluate the safety and efficacy of IT rituximab in progressive MS (EFFRITE trial; ClinicalTrial Registration NCT02545959). Patients were randomized into three arms (1 : 1 : 1): control group, IT rituximab (20 mg, IT) group, and intravenous+IT (IV+IT) group. The main outcome was a change in levels of CSF biomarkers of inflammation (osteopontin). Secondary outcomes were changes in levels of CSF biomarkers of axonal loss (neurofilament light chain) and clinical and MRI changes.

Results: Ten patients were included (2 : 4 : 4). No adverse event occurred. OPN level remained stable in CSF at each time point, whereas NFL had slightly decreased (-8.7%) at day 21 (p = 0.02). Clinical parameters remained stable and leptomeningeal enhancements remained unchanged.

Conclusion: Clinical outcome and biomarkers of inflammation were not dramatically modified after IT injection of rituximab, probably due to its limited efficiency in CSF. Drug issues for future studies are discussed.

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MouseDoctor

8 comments

  • As a Multiple Sclerosis Patient in my Sixties on Glatopa every day, I am Thankful I’m not on the pipeline drugs that try to outdo my poor body in fighting the MonSter in me. I know it’s not popular to study boring, uncomplicated, generic treatments. But feel free to study Me. Not just because I think Glatopa is keeping me stable and young doctors think, well, she’s too old to switch.
    No, for all the Other things I do. Sleep 😴 Using Apollo and now simple Physical Therapy Routine, KTTAPE to a few problem joints. Mostly Low carb diet. It’s a Whole picture, holistic approach.

  • Would be nice to tell those patients that in the past all other trials doing the same aproach, failed

    Sir ….Do you stil want to go ahead with this?

  • Yeah I remember 5 years ago when the NIH reported insufficient absorption of rituximab in CNS tissue after intrathecal injection in progressive MS. The clinical trial was stopped. Maybe they didn’t believe the investigators.

    • Yes indeed but entry to the brain from the blood in every blood vessel is not the same as sticking a big needle in through the skull. I personanlly think DoDo will have incremental impact

  • Yes indeed but entry to the brain from the blood in every blood vessel is not the same as sticking a big needle in through the skull. I personanlly think DoDo will have incremental impact

  • I thought surgeons were the man-gods of medicine. But I agree with your point esp with N95 and VitD. Its similar to debating, everyone wants to speak but no one wants to listen. Honestly, a high-level MS research strategy is needed so we can better allocate research. Has the team considered creating a strategy/plan for research? Seems like a good idea assuming you can get the wide range support needed for it.

    Also, for the sake of god stop making VitD trials. Its like the mask thing, it won’t kill you if you wore a mask.

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