Optimal Dose of Ocrevus for Multiple sclerosis
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- เผยแพร่เมื่อ 2 ต.ค. 2024
- Some evidence suggests that the standard dose of Ocrevus may be too low. Prior research found that those with a higher body mass index (BMI) have slightly more disability progression despite Ocrevus, perhaps because they are effectively receiving a lower dose of the drug. In this video, I review a study which looks at Ocrevus drug levels and its correlation with relapses, new MRI lesions, and disability progression in the OPERA I, OPERA II, and ORATORIO trials. I also give my personal opinion.
Selected sources:
Association of Higher Ocrelizumab Exposure With Reduced Disability Progression in Multiple Sclerosis: nn.neurology.o...
Higher blood levels of Ocrevus lower confirmed disability progression risk: multiplesclero...
Ocrevus product label: www.accessdata...
A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of a Higher Dose of Ocrelizumab in Adults With Relapsing Multiple Sclerosis (RMS): clinicaltrials...
A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of a Higher Dose of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis (PPMS): clinicaltrials...
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Dr. Brandon Beaber is a board-certified neurologist with subspecialty training in multiple sclerosis and other immunological diseases of the nervous system. He is a partner in the Southern California Permanente Medical Group and practices in Downey, California (South Los Angeles). He has several publications on MS epidemiology and has participated in clinical trials for MS therapeutics. You can follow him on twitter @Brandon_Beaber where he regularly posts about MS news and research.
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he video material by Dr. Brandon Beaber is general educational material on health conditions and is not intended to be used by viewers to diagnose or treat any individual's medical condition. Specifically, this material is not a substitute for individualized diagnostic and treatment advice by a qualified medical/health practitioner, licensed in your jurisdiction, who has access to the relevant information available from diagnostic testing, medical interviews, and a physical examination. To the extent that Dr. Beaber endorses any lifestyle change, behavioral intervention, or supplements, the viewer should consult with a qualified healthcare professional to determine the safety and efficacy of the intervention in light of their individualized information.
I am a big believer in the theory that "smouldering MS" is the REAL MS promoted by professor Giovannoni simply because I have never been told I have new or active lesions ("no interval change"), yet it is super obvious that I have very significant brain atrophy and disability progression.
There is no question that "smouldering MS" is real. But what is the best treatment for it? That remains to be seen.
@@DrBrandonBeaber I would love you to do a video on antivirals against EBV as a complementary treatment to anti CD20. The case reports of patient improving on HIV medications are very encouraging to me! Now if someone would just fund the study!
I personally have chose to do 300mg q 6 months. I was experiencing more utis and pneumonia on higher doses. Igg levels low end of normal. When I stopped the 600 mg q 6 months. Igg rose a bit and haven’t had any infections since.
Lowering the dose would certainly be another way to reduce risk. Do you know if your b-cells replete by 6 months?
Dx 2019, female, age 37, just barely in the overweight BMI. Began rituximab 5 months later. Am now doing 500mg Truxima every 10 months. My b cells seem to start coming back around month 9 but are still very low. Have had no disease progression or symptoms since the Optic Neuritis in 2019. Have been wanting to push the infusions to annually. Have had no increase in infections.
Ocrevus lasted around 4 months for me. My Dr. and I validated this through blood work; however, I now take Kesimpta and have had much better results. Kesimpta is holding my cd19 at 0 and has done some for over two years. My walking is much better and no cane is needed anymore for me. This drug has calmed my ms for now. I’m happy!
If Natalizumab is not enough to stop activity then what would be the next step?
I’ve been on Ocrevus since early 2018 except when I skipped a dose during Covid Delta. MRI have been stable since, even though I have worsened. I’m in the smouldering MS camp too. My BMI is healthy under 25. I believe not being overweight has helped me stay on my feet. I’m considering asking if I can do once a year dosing. I’m 68 and my overall health is good but concerned about complications and illness that comes with aging.
Thanks so much for the helpful information you share with us. The more info we have the better decisions we can make.
I get Ocrevus every 5 months because I have a slightly higher BMI and the "crap gap" is a real thing, at least in my case. What percent of your patients opt for infusions every 5 months? The label states it can be given this way (5-6 months) safely.
I don't think the interval is a concern in the short run because many people have no detectable b cells 6 months (or much longer!) after receiving the drug. I am more concerned with people who have no detectable b-cells continuously for many years. There are some people who experience significant b-cell repletion by 6 months, so there is some individual variation.
In Belgium there is no differentiation on BMI or anything else, so everybody gets the same dose of Ocrevus every 6 months. I have been taking ocrevus for 3 years and have been stable since with no new lesions, would you recommend to a patient like that to only start taking in once a year?
I agree about how people are often monitored for CD20 counts and if those are 0 and the goal of Ocrevus is to keep them at 0, taking a higher dose doesn't make sense when you're already at 0. Maybe it's going to end up being another "We don't really know how this works but it's been shown to work in trials" drug 😀 I have had new lesions on Ocrevus, so maybe I should have been on a higher dose, but who knows. Thanks for the videos, always interesting stuff.
Hi, statistician with MS here: I'm annoyed that this is yet another study on this matter, where the researchers discretize a continuous variable for no reason. If the researchers are confident they want to use exactly 3 degrees of freedom on this potentially non-linear effect (3 dummy quantiles and the fourth one as baseline), they can do so by fitting a generalized linear model with a polynomial or spline basis. Personally, I'd use a Generalized Additive Model to obtain the resulting effects. Once you model the data appropriately, the effects can be much stronger. Causal interpretation would still be a problem though.
Wouldn't the infusion issues (like what I experience, a severe throat pinch) be a limiting factor for a high dose? It takes all day to get 600mg in me. Ive been on Ocrevus going on two years now. I am a high BMI 64 yr old male.
Yes this could be a problem for people with significant infusion reactions, though they can often be limited with pre-treatments such as solumedrol/benadryl/tylenol/famotidine.
Dr. Beaber, do you use contrast with MRIs? Do you get a better picture using contrast?
I personally don't use gadolinium for every single screening MRI for MS due to potential risk of gadolinium accumulation unless I think it would help me make a treatment decision.
One of the best of your videos, thank you. What about idea that with higher dose Ocrveus, the more antibodies get into the brain, where B cells also reside. Could it make sense?
Good point made! Imo, besides being in a high enough dose, the MAB should be small enough to be able to cross the blood brain barrier.
About to take my 4th dose soon live in Canada 🇨🇦 and find I have what I would call (Crap gap) so I start feeling really bad about the 5th month- So now they don’t wait until the 6month mark for my infusion, usually get in about 5.5months so I wonder if I need a higher dosage? Hummmm? Not sure if they are doing trials in Canada though- I only weigh 54kgs also so not sure why the drug doesn’t last the whole 6months for me 😢 but I do feel amazing once it does it’s magic!🎉
Dear Dr. Beaber,
thanks again for the video. Actually I was hoping that this was already a video on the results of the MUSETTE study. I agree with you completely on your point regarding the confounding effect of BMI. Actually you could read the results as: What is the impact of different BMI groups under Ocrevus? and learn that people who are lighter (and who overall may pay more attention to what they eat, potentially being part of different countries (I am not sure about the sample etc of the OPERA and ORATORIO studies)) have a better prognosis, duh ... :) However, Hauser and Gavin Giovanoni have claimed that a higher dosis of Ocrelizumab may pass the blood brain barrier and this is what we see in the data. What is your view on this statement?
Another question: Suppose you have started a patient on Ocrevus and you give it to them every 6 months. At what point of stability (suppose no new lesions and no new relapses, no or minimal functional progression) would you choose to extend the interval? How do you treat people who go off Ocrevus or any other CD 20 depleter?
Thanks and best regards!
There is evidence that a small amount of rituximab crosses the blood brain barrier: pubmed.ncbi.nlm.nih.gov/10811510/ I am not sure about ocrevus. I personally think deescalation to a less immunosuppressive agent or extended interval dosing of b-cell depleters is reasonable in many people with MS.
I am newly diagnosed with multiple sclerosis at the age of 43 I'm going on 44 next month and I will be receiving my 1st dose July 22nd
Interesting results...I just received my first 600mg dose of Ocrevus about a month ago. Anecdotally, I noticed my symptoms of fatigue and brain fog stopped within 3 months of my first split dose. It felt as though my MS symptoms went silent, even though I had no active lesions at diagnosis. I did have fatigue for the few weeks leading up to my last infusion, which seems to be commonly reported (so called "crap gap"). I'm hoping to switch to a BTK blocker in the future and regain my b cells. Hopefully, they'll have similar efficacy to Ocrevus.
Exactly my plan too
OK, so after 5 months, I am already on all fours and dying for my next infusion. The MRIs seem stable enough, though there's obviously disease progression. My new neurologist demanded on her authority that the Ocravus infusions be moved up, but the insurance says it's no go. 👎 She wants to try plasmapherasis to cover the 'crap gap', to me it sounds a bit extreme. What's your experience with this treatment? PS, I'm not overweight, BMI 21.
I'm currently receiving Ocrevus every 5 months. I was sliding into the crap gap and my quality of life was terrible. I tend to feel better a few days after the infusion. It has been my last hope and has been wonderful.
Thanks as always for sharing this type of info! I don't take O but am personally most comfortable taking the least amount of medicine to do the job, in this case to keep ms at bay. I've been taking the low dose of Tecfidera for 3 years & have zero new lesions, progression or physical changes (I'm 60). I'd love to see a video on the different dosing options for DMT's, and if there are any studies to support lower than recommended dosing still being effective (i.e., can low dose of Tecfidera still be effective if lymphocytes are low; can extended dosing for Tysabri still be effective etc. Thank you!
What constitutes low dose tecfidera? I do have a video on tysabri extended interval dosing and PML risk: th-cam.com/video/fu0tuD4E6as/w-d-xo.html
Dr Bieber, would you agree that BTK results we have so far have shown they are not as big of game chamger as we hope they would be? (Same relapse rate as ocrevus). Sure, we dont have numbers for BVL but still
see "Biogen bails on btk after 125 million bet"
Thanks for this review dr Beaber! Appreciate you expressed personal opinion (opposed to most being rather hesitant). I'm really interest in double/triple Ocrelizumab dose trials. Problem with these trials is that the only group that can inform on the benefit is the lower weight group, if the higher weight group does better you can say they were underdosed.
We will have to wait for the results of the randomized trials I mentioned at the end of the videos.
A video about the psychedelic therapy for brain damage will be cool. 😊
Do Ocrevus and Kesimpta increase risk of skin cancer?
Only Ocrevus
Dr. Beaber thanks so much for constantly keeping us updated about new scientific studies! Could you make a video about BTK-inhibitors?
I have a video on masitinib but not the other agents: th-cam.com/video/AG0gYGdk_gU/w-d-xo.html
Suggestion for future video. Machine learning (AI) and multiple sclerosis research, are we closer to find that CAUSE?
Fascinating. Thank you! I had my first infusion of Ocrevus last September of 2022. Previously on Tecfidera for 1.5 years. Due to prolonged hypersensitivity after the first dose I chose not to take the second. In December we checked my CD20+19 because I was developing a problem with my speech. It was reported as a definitive B-cell population not identified,
Interesting information-
Ty for breaking this information down for us.
Be skeptical
#Sharingiscaring
#MavencladMilf
Great video, I don't think it is fare to compare the dosage of these agent as they have different epitope binging loci (except RTX/OCR), but the affinity by which they bind to their target is quite different based on they why they do the killing too (CDC vs ADPC vs ADCC).
I am in the tailored approach camp for sure. I don't like the design of these study because it is an experimentation with no theoretical framework that could explain mechanisms.
If we talk about b-cell depletion, then giving more of the dose wouldn't make any sense for 2 reasons:
I'm not sure that we have robus evidence that till us more of the drug would make it last longer, except for potentially ADAs.
Also I'm not sure if we have evidence that higher dose will result in deeper tissue penetration
Finally our tool that guage progression is quite blunt.
The small absolute risk reduction doesn't convince me.
Thank you
Good morning Dr Brandon, I understand that your topic was B cell depleting medications but I was wondering about tysabri and if there could be a different protocol for that besides the 4 to 6 weeks infusions. Thank you again for a very informative video sir
I have a specific video on Tysabri PML Risk & Extended Interval Dosing: th-cam.com/video/fu0tuD4E6as/w-d-xo.html
@@DrBrandonBeaber thank you sir
How does one know if one has antibodies to the drug? ADA's I believe they are called?
Hi Dr. Beaber,
I have a quick question regarding a recent MRI I had. I have spoken with my doctor and she stated that the lesions have not progressed since the last MRI.
She also stated that stable pattern of chronic demyelination means that the lesions have stayed the same since the last MRI.
The findings of the MRI are as follows:
Mild thoracic dextroscoliosis is redemonstrated. There is no spondylolisthesis or loss of vertebral body heights. A small
benign osseous hemangioma involving the T9 vertebral body is redemonstrated.
There is no disc herniation, central canal stenosis, or foraminal narrowing.
Again demonstrated are multiple patchy foci of intramedullary T2 hyperintensity throughout the thoracic spinal cord,
compatible with foci of chronic demyelination. These foci are stable in size and configuration when compared to
9/24/2021. No associated spinal cord expansion or atrophy is detected.
I would like a second opinion of another neurologist just to compare.
Thank you,
There would be no way for me to comment on whether the radiologists interpretation is accurate.
No difference with this infusion
4support =)
Not safe
“For you”.
Didn't work for me