Kesimpta (Ofatumumab) for Multiple Sclerosis [ASCLEPIOS I/II trial results]
Вставка
- Опубліковано 13 сер 2020
- Ofatumumab is a b-cell depleting agent which had two successful clinical trials for multiple sclerosis (ASCLEPIOS I and ASCLEPIOS II) where it was compared against the pill Aubagio (teriflunomide). In this video, I review the clinical trial results looking at relapses, MRI lesions, serum neurofilament, and brain atrophy. We also look at side effects of the drug in the trial.
Comment or ask questions below! I would be happy to answer!
Subscribe on UA-cam for more videos every Wednesday!
Make video requests in the comments section!
My book "Resilience in the Face of Multiple Sclerosis" on Amazon: www.amazon.com/dp/B07WP7H5LK
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.
Follow me on twitter: / brandon_beaber
Music: INNER GRACE - Copyright 2018 Wilton Vought
Source: Really Really Free Music
Link: • Video
The 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. - Наука та технологія
Thks for your videos, it helps a lot to understand differences between drugs and more...
I was actually part of this trial. Very happy I did it as the other meds were not working for me. Haven't had a relapse in 4 years. They recently changed from a regular need to a pen style, which I prefer.
nice
What is a pen style?
@@martinschultz2631like an epipen
This is a great video! I’ve been on Aubagio for a year. Just had an MRI that showed a new brain lesion, so I’m being switched to kesimpta. These numbers are encouraging
I was waiting for this one...thank you Dr. Beaber for taking time out to make this video for us....
When can we expect to see this drug on the market?
Regards.
My guess would be very soon. The drug is already approved for leukemia, and there really aren't any "red-flags" that would concern the FDA/EMA as far as I know. According to this article, the FDA extended its review of ofatumumab until 9/2020 and it is not expected to enter the US market until 2021: www.clinicaltrialsarena.com/comment/novartis-ofatumumab-approval-delay/
@@DrBrandonBeaber thank you for the response Dr.
@@aditya50499 It has in fact been FDA approved: news.bloomberglaw.com/pharma-and-life-sciences/novartis-fda-approves-kesimpta-for-multiple-sclerosis
@@DrBrandonBeaber wow!!! Thank you so very much for this amazing news... I was planning on getting admitted for my second round of Rituximab infusion...I was really praying for it to get FDA approval real soon as it would be a lot safer for one to get the treatment at home (in this pandemic)... Kindly let me know if it can be imported to India...
Thanks in advance.
@@aditya50499 There will probably be some delay until this medication is commercially available. It is actually recommended to be observed for the first few treatments of ofatumumab as it can cause injection reactions. I have no idea if/when it would be available in India.
Thanks!
Hi Doctor... thanks for the amazing video.. you are God sent... I do not miss any of your videos..
Doctor why usually doctors do not start any medication on first attack? even when they are sure of the diagnosis? why they wait for the second attack?
Is it to check if the disease is aggressive or not?
and it would be really great if you can make a video on do's and don'ts for newly diagnosed people about lifestyle which may help them to delay the progression. I will be waiting for this video.
Historically, MS was rarely diagnosed after a single attack, but the recent diagnostic criteria allow for faster diagnosis with a single attack in many cases (depending on MRI and spinal tap results). The historical reason for delaying treatment was to avoid over-diagnosing people and exposing them to unnecessary treatments. For lifestyle advice, I would suggest this video summarizing the advice in the book "overcoming multiple sclerosis" which I recommend: ua-cam.com/video/yExeGBRxIfc/v-deo.html Much of this advice is unproven by in my opinion is reasonable based on best-available-evidence.
@@DrBrandonBeaber Thanks a lot for the reply. Your channel is my first recommendation for anybody fighting with MS.
For any information I resort to this channel....the videos are much helpful and most accurate and appropriate one. Apart from this, you spread a very positive vibes doctor. Thanks.
@@baldipkaur7475 :) Thanks for the compliment!
Hello Dr. Been currently taking Rituxan for 6 yrs with very good results. Due to a health insurance change the Rituxan is going to be very costly. Have an option to switch to Kesimpta. Wondering your opinion of pros and cons between the two. Worth the switch? Thank you.
Which one would be a best pick in terms of side effects and efficiency Ofatumumab or Glatopa?
Thank you for this video. I just saw my Neuro yesterday and spoke to him about this therapy. My first therapy was Rebif so I'm fully aware of the pro's and con's of self injection and once a month vs. a 6 hour infusion every 6 months is an easy choice for me. I'm just waiting for the formal introduction and then to check on costs/insurance. Do you have any opinions about efficacy vs Ocrevus? Sounds like home infusions and "fast" infusions of Ocrevus are becoming more available and I think Ocrevus stands to lose much market share potentially.
I would speculate that Ocrevus and ofatumumab would be similar in efficacy. For the phase II studies, they did a very nice dose-finding study for ofatumumab, so in theory, it may be more optimally dosed than Ocrevus. Ocrevus may be somewhat overdosed, but it is unclear if this makes any clinical difference. You think a once-every-four weeks self injection would be more convenient than a once every 6 months infusion? You do have to do the first few doses with observation just in case you have an injection reaction. I'm not sure how long this observation would be for.
Disability progression is different than disease progression?
How does this compare to Tysabri... so, I lost 100% arm and hand function last year. Got my diagnosis, then got Plasmaparesis and got some function back. Got put on Tysabri but it isn't helping me as much as my doctor has raved about it. Plus going in monthly for the infusion sucks, wondering if Kesimpta could be an option for me. I am not sure why he wants Tysabri so bad for me, wasn't very clear on that. I spoke with Aaron Boster at a Conference in Columbus, OH who said potentially Kesimpta, Ocrevus, or Mavenclad could be an option on top of taking it with Ampyra. Says there's no specific hand function research for Ampyra but theoretically it could work on upper arms in the same manner as it does legs/walking. I already failed Vumerity so Tysabri is my 2nd drug... hate the cognitive side effects as I have Autism and Intermittent Explosive Disorder and Tysabri isnt helping any of my anger/depression episodes. I'm a programmer losing hand function and I'm pretty scared! Any input is appreciated! Thanks
Thx Dr. Beaber! Could you do a video comparing B cell killer drugs? I am considering switching but am having a hard time finding information comparing apples to apples.
I actually already made a video comparing ocrevus and Kesimpta: ua-cam.com/video/BVhN4_sEi1s/v-deo.html
@@DrBrandonBeaber thanks!
Dear Dr. Beaber,
thanks for this great video. One question: How do those studies actually deal with patient dropouts? Are the "success rates" (e.g., disability rates at 7:00 of your video) somehow corrected for the number and the reason of patient discontinuation? If not, then these numbers might suffer a lot from a "survivorship bias". In the worst case scenario, if the study has started with about 944 patients and has ended with only 50 patients and half of those who left due to disease/disability progression, then the resulting fraction of patients with disease progression under Ofatumumab would be around 50 - 60 % rather than 8.1%. Of course this is highly pessimistic but this is an important question when you compare the costs and the benefits of such a treatment. Do you know how the Ocrelizumab studies dealt with patient dropouts and their impact on success rates etc.?
I wish you good health from Germany and thank you for your great service to the MS community :-)
Best regards.
These studies had relatively good retention. For instance, "In
ASCLEPIOS I, the trial was completed by 89.5%
of the patients in the ofatumumab group and by
81.4% of those in the teriflunomide group. In
ASCLEPIOS II, the corresponding percentages
were 82.5% and 82.1%." They do perform secondary analysis accounting for potential biases with selective dropout.
Dr. Beaber: Is there any correlation with making BPPV worse on Kesimpta? I've been having more BPPV attacks since I began a few months ago.
I wouldn't expect Kesimpta to worsen BPPV. I can't give you medical advice, but for many people the foster maneuver is effective for BPPV: ua-cam.com/video/mQR6b7CAiqk/v-deo.html
Dr B, thank you. Can you help me understand the connection between brain volume loss and lesion development? Is the expectation that the reduction in brain volume loss is due to lesion prevention or is there another inflammatory mechanism in the brain?
Sometimes, local volume loss is directly related to a lesion, but there appears to be a low-level "smouldering" inflammation in the brain, even in relapsing non-progressive MS. It is common to have brain volume loss even without new lesions. I have a separate video on this concept of "progression independent of relapse activity" [PIRA] from the JAMA neurology study if you would like to take a look: ua-cam.com/video/duwSGmbHa0E/v-deo.html Professor Gavin Giovannoni has a nice video on "smouldering" MS which he call "real MS": ua-cam.com/video/U38RqkSUYvI/v-deo.html
@@DrBrandonBeaber thank you very much.
Excellent explanation ty have a great weekend. 👌🏼
Thanks. You too.
My wife gets an MRI every year but brain volume loss has never been mentioned. Should that be measured together? Or is that an extra measurement, that needs to be done?
Brain volume is commonly monitored in clinical trials, but to get this data from conventional MRI, special software is required. It is unclear if monitoring brain-volume is helpful for an individual person with MS.
Thank you for the information, my neurologist seems to like this drug and its effectiveness. I'm concerned about long term use and of course infections, cancer. Is there any information on long term effects?
Not really as far as I know. Arzerra (intravenous ofatumumab) is used for chronic lymphocytic leukemia and generally isn't given on a long term basis. My suspicion is that Kesimpta would have the same problem as rituximab and Ocrevus, that you can get low immunoglobins with continuous long term use, increasing the risk of infections. In terms of cancer, there is a possible increased risk, but this isn't fully known.
@@DrBrandonBeaber Thanks! I appreciate the answer :)
How would you compare this medication to tysabri as far as effectiveness?
They've never been studied head-to-head but are likely similar in efficacy. ofatumumab is better at suppressing enhancing lesions. Some indirect comparisons from real-world-data suggest that other b-cell depleters (ocrevus, rituximab) are similar in efficacy to tysabri.
Why did they exclude people with canes from the study? I thought this thing was supposed to be good for secondary progressive MS.
They may do a separate study on this. Often it's difficult to show differences in EDSS at EDSS 6 or more, so from a research perspective, it causes a problem. I'm going to do a video later on why we should stop using the EDSS and switch to the MS functional composite.
Why is it compared to Aubagio? why not compare it with Ocrevus for example
They want to may their drug look good by comparing it to a lower-efficacy agent.
Dr. Beaver, I'm doing well on Ocrevus. In your opinion would there be any reason to consider changing?
I am responding well to Ocrevus and 2 days a year for infusions has not been an issue for me. For those reasons, I plan to stay on Ocrevus for now. I like the idea of knocking down the B cells more often. Hope this drug does well. Looks like it is a bit less expensive than Ocrevus as well
@@DumbDadDuties One advantage of Kesimpta is they did a very nice phase II dose-finding trial, so it may be more optimally dosed than Ocrevus. It is unclear if this makes it safe in the long run. I'm not sure about the cost (maybe this hasn't been fully determined yet).
How would this drug fare in a case of SPMS with relapses? I keep trying to talk my medical team in to secukinumab, as I have both SPMS and Psoriatic Arthritis. I was told the data for Secukinumab is not promising for MS.
I would imagine ofatumumab would perform similarly to rituximab or ocrevus. Technically, the trial for rituximab (OLYMPUS) and for ocrevus (ORATORIO) are PPMS trials, but in my opinion, SPMS and PPMS are the same disease. Secukinumab is an anti-IL-17 agent. This class of drugs is thought to be not highly effective in multiple sclerosis, but this is not 100% known.
@@DrBrandonBeaber thank you so much for your reply.
I changed from tecfidera to kesimpta and i’m taking my third injection today
Good luck to you.
Another question...if a person injecting Ofatumumab does so without any adverse side effects, how likely is that person to remain mostly free of said side effects...and vice versa?
In terms of injection reactions, my guess is that reactions would be most severe with the first few injections because this is true with the first few infusions with rituximab and ocrevus. In terms of risk of infections, my guess is this would actually increase over several years with continuous use. The reason for this is that some b cells turn into plasma cells which do not have the CD20 receptor and are immune to all of these drugs. Hence, people taking these drugs often have normal immunoglobin levels at first . In the long run, if you don't regenerate plasma cells, immunoglobin levels can drop which is a known risk factor for infections. With rituximab, neurologists often recommend giving it less often later on or if immunoglobin G levels are low. There is not specifically defined guideline though.
@@DrBrandonBeaber so, does it mean that after using Rituximab or ocrevus for several years, there are chances that the drug becomes less effective due to b cells turning into plasma cells and IgG levels getting low?
Or does it mean that it works even better and we can cut back the schedule to a less frequent schedule when it gets to that point?
I just started Kesimpta yesterday. I'm a 56-year-old female and I have Active SPMS. I'm also on IVIg every 8 weeks. I had COVID-19 in December and I do plan on getting the when I can. My QUESTION is this: My MS doctor told me it was okay to start Kesimpta now and I can still get the vaccine when I can (I have immunity for at least 3-5 months according to Health Department). I know the vaccine is a non-live vaccine but the literature does say that even non-live vaccines should be given two weeks prior to starting Kesimpta. What is your opinion on this? Thank you!
There is evidence that b-cell depleting medications such as kesimpta could reduce the effectiveness of vaccines. I do have a video on this topic: ua-cam.com/video/oAjqCmudqxM/v-deo.html Generally speaking, I am advising my patients to go forward with the vaccine because the surge is happening now, and a partially effective vaccine now may be more valuable than a fully effective vaccine later. Talk to your own provider.
@@DrBrandonBeaber Thank you!!
Hallo, may this new drug have an positive effect for patiens with ppms without active lesions?
PPMS wasn't entered in the study, but I also like to know if Ofatumumab theoretically would be usefull for PPMS like ocrevus for example.
I'm waiting for the ppms treatment that will make a difference for the quality of life
@@EarSlade23rd I hear you Dana.
@@TheSokwe You are absolutely right. I would speculate that any b-cell depleter would be equally effective in PPMS, though ofatumumab has not been explicitly studied in PPMS. The ORATORIO study (Ocrevus in PPMS) and the OLYMPUS study (rituximab in PPMS) have remarkably similar results. As I said all of these drugs eliminate virtually all b-cells very quickly.
Quero que Traduz em português....por favor....
aubagio shot my blood pressure up to 245/101 definitely understand how he died
Will a coronavirus vaccine be safe for those with Multiple Sclerosis??????
I can't say that this is specifically known. Studies generally suggest that vaccines are safe in MS and do not trigger relapses except for the yellow fever vaccine which is known to trigger relapses. Source: jamanetwork.com/journals/jamaneurology/fullarticle/1108041 There are a lot of different potential covid-19 vaccines, but generally speaking, they are killed-vaccines which should be safe despite the use of disease modifying therapy. Certain disease modifying therapies like rituximab or ocrevus could decrease antibody response, limiting the effectiveness of the vaccine.
@@DrBrandonBeaber Sep 9 info shows astra zeneca covid vaccine is not as safe as we expected: www.statnews.com/2020/09/09/astrazeneca-covid19-vaccine-trial-hold-patient-report/
Hi is it possible myelin sheet repair plz guide me
Thanks
I may do some more videos on potential experimental remyelinating agents. I do have one video on clemastine: ua-cam.com/video/T6p5e2TcR9Q/v-deo.html
@@DrBrandonBeaber that would be great... We have been waiting for you to talk about such trials
@@aditya50499 If there is a certain potential remyelinating agent you are interested in, let me know. I would probably do anti-LINGO (opicinumab) since it has the highest probability of being an approved drug.
@@DrBrandonBeaber elezanumab by AbbVie, Mesenchymal stem cell therapy trials by Tisch MS research centre and brainstorm cell therapeutics (NurOwn) investigating bone marrow derived neural progenitor stem cells. Also, it would be great if you could speak on T cell vaccine (Tcelna/ Tovaxin or Neurovax or some other B cell vaccine) for MS.
I know sir, the list is long but so are my MS symptoms and the hope that I will be able to get better and eventually normal again.
Thanks in advance. I really wish we could have Neurologists like you here in India.
Regards.
@@aditya50499 thanks for the suggestions. I'll make a note of them.
What is everyone’s out of pocket cost for kesimpta? Reply to this here. Thanks
I would be interested to see the responses
I’ve asked the same, still waiting
Lets have some fun 😁
Isn't reviewing data from clinical trials fun!
This drug can heal MS
why would you say that?
fix your title, ofatumumab
Whoops. Thanks.
They say it's better than garbagio. So that's good. pretty sure anything is better than garbage tho.
believe it or not aubagio was the only drug that worked for me until it started to destroy my liver