MS Treatment De-Escalation

[@garyrooksby]

Hi Dr. Beaber. This is a fascinating video. I'm Male, 58, RRMS since 1996, EDSS 4. I've been on Ocrelizumab since April 2021. My MS team is trialling a deescalation programme and I'm part of it. After 6 months I'm having monthly bloods looking for B-cell count. When I get to 1.0 I have my vaccines and then leave it for another month before my next infusion. Currently, I'm lasting about 9 months between infusions and I've still had no relapse since 2022 (work stress-related. I've since retired). It's working great on our trial and they're pushing for a formal trial nationally here in the UK. I've sent a link to this video to my MS Specialist Nurse and I'm sure she'll discuss with the consultant. Thanks so much, sir!

[@DrBrandonBeaber]

Doing frequent blood tests is one option, but the observational data essentially show that b-cell counts are not very strongly linked to disease activity. Also, doing monthly blood tests is very inconvenient.

[@ellie698]

That's interesting to hear that this is being trialled in the UK. Thanks for sharing that. I've just had my first round of Ocrevus. It would be great to have it as infrequently as possible but still retain the effectiveness.

[@MS-pw6ur]

One factor for some of us to consider aside from risk/benefit is dependence on the medical system. There's always a little bit of anxiety that comes from knowing my disease progression (or lack thereof) is reliant on my health insurance status and the medical supply chain running as it currently does. For me, that means going on a strong DMT *now* while I'm young so my chances are better if for any reason it's not an option to me in the future. De-escalation makes 10x more sense than escalation.

[@DrBrandonBeaber]

You make fair points.

[@andrewreisinger6860]

So difficult to decide what to do with age and de-escalation. I personally think that MS is ALWAYS active, whether or not someone has new lesions or not. If a person is not experiencing increased infections/side effects and can financially withstand the cost barrier for high efficacy DMTs, then I see no reason to de-escalate. I've had MS for over 30 years and haven't had an attack for 15 years (at least), but am also in SPMS with the slow insidious worsening of disability (6.5 EDSS). On Ocrevus now, might switch to Kisempta.

[@saharanights3518]

Kesimpta didnt do nothing for me, they advised me to take Ocroves.. but right now am fedup with all medication, i will try good food and vitamin thats it

[@uptoeleven]

Ocrevus and kesimpta are both B cell depleters. What about trying something like Mavenclad or lemtrada / campath?

[@annmariemoreno3904]

I finished second year of mavacald 10 mg going for MRI today praying for best been 24 years with MS now have secondary MS.

[@Ms.Pronounced_Name]

I finished my 2nd year of Mavenclad almost 4 years ago and I haven't had a new lesion since I started the drug, RRMS not secondary. Hope it's as effective for you as it was for me.

[@annmariemoreno3904]

@@Ms.Pronounced_Name yes praying hard !!!!

[@josephvered3991]

Hi from Israel very interesting video thanks dear doctor

[@EvenSoItIsWell]

Thanks Dr. Beaber! I really appreciate you diving into this topic. Could you do a video on increasing disability as we age even with NEDA? Is it brain shrinkage? Is it comorbid conditions? Is it smoldering MS? Or is it not really a concern? Thanks!

[@ahmedfowad6882]

Thanks for the information. Nice video! A bit strange was a short video "MS drugs are overrated"

[@DrBrandonBeaber]

I don't have a definitive answer to this Vickie, but in this video, I explain 6 theories on the cause of progressive MS: kzbin.info/www/bejne/goKvg3ytgZKUaMU

[@EvenSoItIsWell]

@@DrBrandonBeaber thanks!

[@timothycarter9208]

Those pesky microglia

[@stonz42]

I’ve been on ocrevus for 2 years and I’m glad you addressed this topic. I’m unsure of how long I can continue on ocrevus, but I’ve been neda3 for a year and a half and haven’t had any serious side effects. I’m hoping to eventually transition to something less suppressive in the long term, but I’m feeling great at the moment and my bloodwork has remained stable for over a year. However, I would consider a lower efficacy treatment if my immunoglobulins declined to below normal ranges.

[@__Wanderer]

Very interesting! I wish Netherlands would use the principle sweden does. Neurologists prevented me from taking Ocrevus... When I asked about taking it (i was diagnosed 2 yrs ago) they stated "no too risky someone died of it".... What horrible bedside manner and utterly ridiculous response. I am now on DMF /vumerity but do wonder if I am shooting myself in the foot. I appreciate the frank discussions and want to base my decisions on data like the articles you presented. The rebound factor is why I avoided going for gilenya / siponimod (mayzent) - instead opting for vumerity with similar ARR. I don't want to have a massive life altering relapse because of meds following a swap to another medication at some point.

[@DrBrandonBeaber]

Unfortunately I have seen numerous rebound relapses in my career for various reasons (change in insurance, pregnancy, moving to a new location, etc)

[@__Wanderer]

@@DrBrandonBeaber That is unfortunate to hear. I was personally surprised it wasn't initially mentioned during my conversations with the MS nurse. I think knowing about the risks of rebound activity resulting from medication is crucial :) Thanks again for everything you do!

[@HurricaneHeather]

I went straight to Cladribine for DMT when I was finally Dx'ed last year (after being untreated for likely 30 years). With my cruddy veins, infusions weren't a good option. Have had my second year and the crash from the B-cell depletion has been less than fun. Looking forward to getting a somewhat new immune system. Oh, and I am no longer anemic. The funky stuff with my red blood cells has improved. Only MS related drugs I'm taking now is Baclofen. I am grateful it's not more. I always find your videos very informative. Thank you for your help!

[@briandaniel6354]

My doctor is already starting to lengthen the time between doses for retuximab. I just started retuximab a little over a year ago, but it seems like she is looking at my activity on MRI's and mobility improvements to make a determintation on when I recieve my next dose. After the initial 2 doses 2 weeks apart the other ones have been spread apart more so. 7 months on the next dose etc. The only relapse I had was before I was diagnosed with MS so it does seem to be working and it is always lovely to see "before" and "after" MRI's were disease activity goes from very aggresive to non existant.

[@RahatAsghar726]

Is Rituximab effective??

[@briandaniel6354]

@@RahatAsghar726 ​ It has been for me, I would encourage you though to talk to your own doctor to make a more informed decision. My situation is some what unique. I had a very minor symptoms in MS for 15 years before enough damage had be done to make it more visible .None of my symptoms were interfering with my life in a meaningful way, until 2021 were the dam esentially broke. Because my diagnosis came late in to having MS my doctor decided to put me on Tysabri, then switch to Lemtrada, which had to be changed to retuximab because of the insurance companies denial of Lemtrada. I am happy though, the recovery for me has been great, and as I mentioned the medicine intervals have been extended as well as MRI's. The only relapse I have ever had was prior to diagnosis and the only reason I can say that is because of talking with my doctor. She said 15 years ago I had an inital attack, then went into remision until 2018 were the disease was continualy doing damage until 2021 when I got a diagnosis and was fast tracked into getting treatment. The aggresive treatment plan was because in 2021 I was borderline paraplegic so something needed to be done fast. I can not really work at the moment, but I am getting closer.

[@mccorn75]

Nice topic Dr. Beaber! I feel that high efficacy meds at the beginning improved my outcome and my neurologist has already talked about stopping treatment after 50 because I was stable for over 15 years. However, I wondered if you had information on the impact of menopause and MS. The last two years have brought more symptoms and lesions as I move from peri menopause to menopause. How do hormones impact MS? Thank you!

[@DrBrandonBeaber]

You may appreciate this video on estriol: kzbin.info/www/bejne/ZnPUaqOKdpyimNE

[@barbm1231]

Thank you for the video and information. I'm meeting with my neurologist next week and we already agreed to discuss extended dosing of kesimpta.

[@DrBrandonBeaber]

I think using kesimpta less often is done less often, but we may be seeing more and more of this.

[@barbm1231]

@DrBrandonBeaber I'm 66yrs old, stable for 3 yrs, and following a strict diet and life style. Ready to be the guinea pig 😀

[@ellie698]

​@@barbm1231 What diet do you follow please. 🙏🏻

[@barbm1231]

@ellie698 I follow Wahls protocol but most diets agree no gluten, no dairy, no added sugar, minimal processed foods. Wahls is very specific and strict.

[@DrBrandonBeaber]

@@barbm1231 The Swank and OMS diets are not gluten free.

[@14sgs]

I appreciate all the comments. Esp the ones that tell their story. For me: 57 YOM. Diagnosed at 55 w/ Heavy Burden of lesions in Brain and Spine. =>RRMS At 56 changed to => PPMS Taking Rituximab (3 sessions to date) 1000mg, 500mg, 500mg. 1) Nortriptyline - 30mg (2x day) and 2) Gabapentin-900mg (2x day) I feel like a battery and every day is a little bit different. Mornings I'm at 3/4 charge. Late evenings difficult 20% charge left. Sometimes using a cane at night. Good sleep is essential. I've lost 30lbs in 7 months. I'll take it. (250-30)=220lbs

[@AlexAlwaysWins]

I am male 32 years old diagnosed 16 years. I am just at one year on ocrevus. My first year went well I did not get sick or have any new attacks. I still think about when or how I will de-escalate because compromising my immune system for so long makes me scared of infections. The funny thing is I researched and talked about de escalation with my doctor before I even took my first dose.

[@ernietollar407]

This has made me lean more strongly to avoid DMT in future - I'm almost 60, diagnosed with PPMS in 2022, ocrevus jn 2023, mexican hsct 2023. EDSS maybe 4 (re standing walking). my first MRI this spring/post hsct had no new lesions etc, so If my disability stays about the same I won't go to dmt's unless next year's mri shows new activity. I may have worsened slightly since hsct (but I am just 9 months post hsct so possibly things could go favorably).nIf it's just smoldering damage I'm not thinking there's likely not any way to deal with that other than being active ,well rested and happy as I grow older

[@lauracarlson9260]

Last year I considered changing from Ocrevus to another option for many reasons. One is that I watched a video by Dr Boster from several years ago - Deescalation during a global pandemic- moving from Ocrevus to Aubagio or Mavenclad. As there is a strong history of cancer in my family he said Aubagio would be a better option. I have been MRI stable for 7 years but still experience progression. My last MRI did start showing some brain atrophy beyond normal for a 59 yr old. The interview on your channel with Dr Hauser clinched my decision- how those on B cell depleters don't have attacks or MRI changes but still have progression. Doesn't seem necessary to stay on a DMT known to stop attacks if I'm no longer having them. I haven't had major infections or illnesses but look forward to my B cells returning. I have more lab work so we'll see if 18 months since my last infusion I start seeing them come back. Nothing in my last set pf panels- I haven't noticed more progression or any issues with switching to Aubagio 7 months in. I stopped working last year due to issues with my manager. He was being increasingly challenging on my performance in a complicated role in systems accounting. I took a full neuro psych eval that showed new deficits and a statement I should not return to work in that environment. I applied for SSDI and it was approved in 8 months. Until I have medicare I will have issues finding insurance to pay for options like Ocrevus. I am paying OOP for an Aubagio generic for less than $30/month.

[@lenamafalda]

Since I was diagnosed just last year with MS and followed this aggresive approach with Tysabri, I haven't witnessed de-escalation yet. I feel it will largely depend on the results of my next JCV test. Since this Year's MRIs are very good I hope I will stay JCV negative for longer time and de-escalate later.

[@elizabethrash7370]

Do you think B cell depleters, such as Ocrevus are worth the risk of infection in people with PPMS? Thank you

[@DrBrandonBeaber]

In many people, yes. Some people, due to their comorbidities have a much greater risk of serious infections. The average age in the oratorio trial (ocrevus vs placebo in ppms) was around 43, so it's hard to weigh risks and benefits in a much older individual.

[@elizabethrash7370]

@@DrBrandonBeaber thank you :)

[@WA46-ev3yy]

I deescalated from ocrevus (had infusions for 3 years) to mavenclad due to Covid. Have not had new lesions but have had progression of cognitive symptoms. The new data on people on Ocrevus for 10 years looked strong for disability progression and limited side effects, would be interested to see your perspective on that data.

[@jimsperlakis5634]

Dr, I started on Avonex, @ 56, when a severe neck fusion(c2-t3) put my rrms into gear But reactions caused me go to Copaxone. 4yrs of progression and I was switched to Solumedrol/Techfidera and Aubagio. Then Tysabri was tried for 17 months. @63, I had (2) x Lemtrada. At 69, Rituxamab, 1gm/3month x 2yrs is reduced to 1gm/6mo. After listening to your talk, I'm going to ask Dr about changing to yearly. I'm going to request 750mg thou.

[@existentialdetective2010]

Have been on Kesimpta for a year. Have had MS for 21 years. I did not go to allopathic doctors untill last year. Had random relapses which i treated myself with corticosteroids orally. My disability is 2.65. Now I plan to get off Kesimpta because i started having chronic serious bladder and urinary tract infections. Its counterintuitive to me to further weaken my immune system. I started HRT with estradiol and that helped condition worsening whichbi used to get one week before my period..RR MS is a hormonal issue - something deep down in my core tells me that...

[@Elem70]

I’m just thankful for science so we don’t have to rely on random people’s “feelings” to treat or cure our diseases

[@harrisonfnord5871]

I started Kesimpta in May this year (living in Germany, so no problem with insurance), it went in pretty smooth, no side effects, but i guess the only thing i can do right now is wait and see what happens. I have dozens of asymptomatic brain lesions and 5 pretty symptomatic spinal lesions, and if the yearly mri shows no additional lesions, i plan on taking K for max. 2 years, switch to a lower yield drug and see what happens.

[@NicsGamertag]

Hey Dr Beaber. As someone with MS who consumes everything MS. I am actually self delaying my Kesimpta dosing for a very similar reason that the Opinion Article brought up. All research points to using biomarkers of B cell repopulation or total CD20 count versus a standard 4 week cycle. I'm currently taking the drug every 6 weeks and soon going to every 8 weeks. I actually go to the Rocky Mountain MS Center as well. I wonder what they'd think about it.

[@cnt2495]

Very interesting... I'm a 28 year-old male with RRMS. My neurologist hasn't given me a number on the EDSS yet but I have weakness in my left knee. I'm currently going to PT per my neurologist's request. I've been on Ocrevus since 2021 I believe. I haven't thought about taking Ocrevus longer than once every 6 months. I haven't had a relapse since I was diagnosed back in 2016. I started off with Copaxone and then moved to Ocrevus. I don't want go back to Copaxone because every other day injections suck a lot.

[@DrBrandonBeaber]

You are not the only one who doesn't want to do a self-injection every other day.

[@luciece]

Speaking about 1000 vs 500mg Rituximab, do u think weight adjusting of doses with B cell depletors would be reasonable, considering 50kg person basically gets doble the dose compared to 100kg person? Thanks for good video as always!

[@DrBrandonBeaber]

This is an interesting point. Data from the ocrevus trials suggest people with a higher BMI may experience a lower benefit and could potentially receive a higher dose. One retort I have is, "What is the evidence that 1000mg of rituximab is more effective in a 100kg person?"

[@luciece]

@DrBrandonBeaber there's a double/triple dose Ocrelizumab (weight adjusted) trial going on, curious how this one ends up

[@DrBrandonBeaber]

@@luciece I am as curious as you.

[@jimsperlakis5634]

I didn't receive the start-up doses of Rituxamab, just 1gm/6month with extensive blood tests every month because of the Lemtrada. I'm now 1gm/6mo but thinking about stretching it out to 1gm/yr.

[@jennifermontgomery7470]

I took Mavenclad 6 and 5 years ago for RRMS and have had no DMTs since. I’m now 63 and have also had no relapses. I would consider that process as going from a full on , high efficacy drug to none, a major de escalation. I’m now interested in which DMT has the most efficacy for preventing brain volume loss as that is now my main concern!

[@__Wanderer]

Should check out the studies on alpha lipoic acid for brain volume loss. Most drugs focus on stopping relapses from what I am aware. Perhaps there is some upshot to these drugs but I am unaware. I agree that this should be a bigger priority with the MS community - brain volume is most definitely tied to long term health. Halting this is HALF the issue not just stopping lesions and relapses.

[@nonameavailablerlb]

Don't relapses slow down or stop as a person ages because they have had MS longer? I'm wondering about outcomes for progression when using a de-escalation model.

[@DrBrandonBeaber]

Yes relapses decrease with age. This video is based on observational studies. Ideally we would do more randomized trials.

[@donnabolt5847]

How do you deesculate from tysabri with rebound relapses? Thats a huge fear tbh. My ms is so aggresive i cant even imagine how horrific rebound would be.....

[@jimsperlakis5634]

I didn't listen when they wanted to put me on Tysabri. Instead I did nothing but my ms didn't. I've been paying for that for 14yrs and Now it's ppms and i can't walk! Please don't stop your meds. We need them.

[@donnabolt5847]

@@jimsperlakis5634 😥 I am so sorry. I truly hate this disease.

[@timothycarter9208]

Thank you so much for the video! My humble observations: my wife has had 5 UTIs in the last six months (while being on Ocrevus). The increased symptoms (mainly increased spasticity and urinary frequency, and also cognitive symptoms associated with UTI) in my opinion negate any possible benefit from Ocrevus. She is 43, and has had MS over 25 yrs. When I mentioned frequent UTIs to her neurologist, she said “yeah, that’s one thing about this medicine, is the increased infections “ No other comment. Further points to mention: our immune systems weaken as we age, also without anyway to keep microglia from attacking the brain and nervous system we are just taking shots in the dark. Is there a way to tell what type of lesions (from your previous video) the patient has? They all are effected by different immune cells. Thanks!!!

[@yukas66]

Any data on de-escalation for Kesimpta? Also, any data for those who don't de-escalate gradually, but stop completely at once? Thanks!

[@ellenbrown2348]

64 year old female on Avonex for 20+ years. Is Avonex considered high effacacy? I have been seemingly very stable on it with no lesion activity for a very long time. Would increasing the length between injections be an option?

[@monicapascualalmagro1238]

Hello, I am 34 years old, I have been diagnosed with RRMS for two years. My treatment has been kesimpta for a year and a half. but I don't see myself with this type of treatment long term. Do you think BTK will be more effective and safer for RRMS? Do you think neuroprotective or remyelinating treatments will emerge in about 5-10 years?

[@ernietollar407]

Would you consider a vid/on theraplate for MS..... it has an equine use!

[@DrBrandonBeaber]

I would have to look into it.

[@drlangstoc]

Maybe I missed it, but no discussion of discoms?

[@olgsi]

Do you think that the future, i.e. the next few years, is optimistic in stopping the progression of the PPMS?

[@DrBrandonBeaber]

Unfortunately, I think it is unlikely a new agent available in the next few years would completely stop progression in everyone with PPMS. However, it is possible that drugs such as the bruton's tyrosine kinase inhibitors will be more successful than any existing treatment. We will just have to see how the clinical trials pan out.

[@olgsi]

@@DrBrandonBeaberCan someone who is 21 years old diagnosed with PPMS expect not to end up in a wheelchair in ten years, due to current and future therapies. Are there any cases of people with PPMS whose condition is stable? My mother also has PPMS diagnosed at 27. Thank you for your videos and dedication!

[@theledolee8485]

I was diagnosed with RR MS about five or six years ago and started Rituximab therapy 3 years ago. I stopped therapy a year ago after having symptoms that didn’t match up with MS. Is there a correlation between MS and Long Covid?

[@Nasty3232]

Hello! Is there any research on people with MS and HIV both? Do they do worse than an average person with ms because of it or maybe better on the contrary? Ms is an autoimmune disease, hiv weakens your immune system. And how does hiv medicine affect ms? Couldn’t find any information about it on the internet

[@Ryanwinter84]

What is your opinion on Interleukin 10 helping autoimmune diseases like multiple sclerosis? I have read some studies that talk about Interleukin 10 being a powerful anti-inflammatory that can help regulate autoimmune diseases. Would it be safe for me to take?

[@DrBrandonBeaber]

IL-10 is linked to a TH2 lymphocyte response, similar to what is induced by beta interferons. I am not aware of any direct evidence on using IL-10 as a treatment of MS.

[@Ryanwinter84]

@@DrBrandonBeaber Thank you!

[@brianguppy7693]

On the topic of de-escalation / maintenance therapies, any thoughts on vidofludimus calcium?

[@DrBrandonBeaber]

This is a dihydroorotate dehydrogenase inhibitor similar to aubagio/arava and could potentially be used as a deescalation agent.

[@bmiller949]

Both of these countries have better national healthcare systems and better diets.

[@PrincessPeachh]

Does Aubagio have rebound effects?

[@kevineeverhart7869]

Way off topic here, but i for 1woiuld like to hear what your police force father has to say about last weeks kerfuffle in PA at the former presidents rally on Saturday....which acually kind of fits within any discussion of escalation v de-escalation, wheter it relates to rogue & criminl lymphocytes in our own bodies or rogue & criminal behavior in places like a political rally. Keep up the good please . Say hey to Daddy Beiber, even if he declines not to step into this arena Regards, k

[@dy-no-mitedragon7759]

Hi Dr. Being a neurologist can you tell if someone like the President has dementia or normal aging. I think this would make a good video due to everyone being a neurologist and ready to diagnose the president. What your opinion Without seeing the individual?

[@timothycarter9208]

What current MS medications increase the rate of dimentia/Alzheimer’s? Does the MS population have a higher rate of dimentia/Alzheimer’s? And, is it ethical to prescribe medications such as antichologenics (suspected to increase dimentia onset) to someone with established brain lesions?