Barts-MS rose-tinted-odometer: ★★★★★ (rose-red; a climbing rose with thorns)
I have moved my treatment goal beyond NEIDA (no evident inflammatory disease activity) for my patients with MS. The new focus is on preventing end-organ damage. To achieve this we need to take off the blinkers that the Pharma industry has blinded us with. Our treatment target has to be smouldering MS, i.e. stopping disability progression, normalising brain volume loss, flattening neurofilament levels, stop slowly expanding lesions from getting bigger, clearing the CSF of oligoclonal bands and if possible promoting repair and recovery of the nervous system.
What good is to be free of relapses and focal MRI activity if you are getting worse? This is why the concept of using low dose anti-CD20 therapy is so flawed. It is clear that study subjects exposed to lower doses of ocrelizumab in the phase 3 trials did as well as those exposed to higher doses in relation to relapses and MRI activity, but not in relation to worsening disability (see slideshow below).
From this post-hoc analysis, it is clear that you need higher, and not lower, doses of anti-CD20 therapy at least initially as an induction strategy to purge the various B-cell compartments. We hypothesise these compartments house memory B-cells, which may be an important sanctuary for latent EBV and/or the highly autoreactive population of B-cells that drive and maintain the MS-state. This population of cells may reside in the deep tissues and/or the central nervous system. This is why we and others are testing CNS penetrant anti-B-cell strategies (ixazomib, cladribine, BTK inhibitors, etc.), i.e. we are going beyond the peripheral B-cell target.
However, I have hypothesized that once you have purged these compartments, say after 2 years of treatment you may not need to maintain such high doses of anti-CD20 therapy that will then suppress normal B-cell biology and immune responses, which result in long term complications. This is why I have proposed using ocrelizumab as an immune reconstitution therapy, i.e. high-dose upfront followed by no treatment and wait to see if MS remains in remission or disease-activity returns requiring additional courses. The latter is what we are proposing to do in the ADIOS study.
Even better would be two years of induction therapy with high-dose ocrelizumab followed by a maintenance therapy such as teriflunomide, leflunomide, IMU-838 (vidofludimus) or ASLAN003 (selective second-generation DHODH inhibitors), HAART (highly active antiretrovirals), famciclovir or another anti-EBV viral agent.
The hypothesis is to allow B-cell reconstitution after anti-CD20 therapy in the presence of an antiviral agent to prevent EBV reactivation and reinfection of new memory B cells. By doing this you will also be derisking the long-term immunosuppression associated with anti-CD20 therapies and prevent the development of hypogammaglobulinemia. This strategy will also allow patients to respond to vaccines.
However, if you want lower dose anti-CD20 therapy you will be able to start Ofatumumab very soon. Please remember ofatumumab was vastly superior to teriflunomide in suppressing relapses and MRI activity (Pharma’s blinkers) but was not superior to teriflunomide at slowing down brain volume loss in year two of the ASCLEPIOS I and II clinical trials (NCT02792218 and NCT02792231). Why?
The following is the fundamental question you should ask yourself.
So what would you choose your MS to be treated with; (1) low-dose anti-CD20, (2) high-dose anti-CD20, (3) high-dose anti-CD20 therapy followed by a maintenance treatment or (4) an immune-reconstitution therapy (cladribine, alemtuzumab or AHSCT)?
Sadly we can’t offer all of these choices to all of our patients with MS in the current NHS treatment landscape.
Hauser et al. Ofatumumab versus Teriflunomide in Multiple Sclerosis. N Engl J Med. 2020 Aug 6;383(6):546-557.
Background: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known.
Methods: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume.
Results: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P<0.001) and 0.10 and 0.25 in trial 2 (difference, -0.15; 95% CI, -0.20 to -0.09; P<0.001). In the pooled trials, the percentage of patients with disability worsening confirmed at 3 months was 10.9% with ofatumumab and 15.0% with teriflunomide (hazard ratio, 0.66; P = 0.002); the percentage with disability worsening confirmed at 6 months was 8.1% and 12.0%, respectively (hazard ratio, 0.68; P = 0.01); and the percentage with disability improvement confirmed at 6 months was 11.0% and 8.1% (hazard ratio, 1.35; P = 0.09). The number of gadolinium-enhancing lesions per T1-weighted MRI scan, the annualized rate of lesions on T2-weighted MRI, and serum neurofilament light chain levels, but not the change in brain volume, were in the same direction as the primary end point. Injection-related reactions occurred in 20.2% in the ofatumumab group and in 15.0% in the teriflunomide group (placebo injections). Serious infections occurred in 2.5% and 1.8% of the patients in the respective groups.
Conclusions: Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide. (Funded by Novartis; ASCLEPIOS I and II ClinicalTrials.gov numbers, NCT02792218 and NCT02792231.).
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.
As a current ocrelizumab patient, who has continued to have sensory relapses during the first 12 months of treatment, i would be tempted to give option 3 a go if it was on the table as i have not had any issues with tolerating the drug. However, as it is not on the table i am currently pursuing option 4. I was all set for HSCT abroad but suddenly alemtuzumab is being offered now so my head has been turned. All things being equal, my preference would still be HSCT as a treatment option but cost, the need to travel, leave the family, timing of the treatment are all factors that weight against it at present
May I ask what is sensory relapses – do you get new symptoms?
Hi Karage, i dont know whether this is a definitive term but i have seen it used previously so adopted it. Yes, new or recurrent symptoms – pins n needles, numbness, muscle twitching etc. Nothing that stops me doing anything but a clear cut exacerbation of symptoms. I would class them as mild in so far as they are not disabling relapses
Hi ANNONYMOUS, Thank you for your reply – I have similar “sensory relapses” so find your comment very interesting and couldn’t help to comment, thinking with my layman’s knowledge that these might not be relapses – if sensory pathway is damaged, transmission/interpretation of signals can be off, if you are exposed to unusual signals (say going into winter when onset was in summer) during a stressful day, this could give you “new interpretation” of the cold, which you never experienced before. Assuming you don’t have MRI activities, this may not be deteriorating.
Anyway good luck with Alem or HSCT! Please let me know if they work on these sensory relapses!!
“who has continued to have sensory relapses during the first 12 months of treatment,”
If it’s not connected to a specific relapse w/mri lesion…then it would seem more likely
just to be labelled as progression. PIRA…progression independent of relapse…What’s the story about the boiled frog..it started out as just little heat..it started out as just sensory relapse but it can lead to weakness/spasticity.
I’m seeing recovery on many aspect however weird/different sensory still visits. This is not denying progression exist but these sensory issues may not be evidence of it. Would be great if a doctor could comment on this….
“Would be great if a doctor could comment on this….”
They tend to not comment on requests.
It depends if they have time and also if it is considered as specific advice
“I have moved my treatment goal beyond NEIDA (no evident inflammatory disease activity) for my patients with MS.”
Yeah! The “real / smouldering” Prof G is back. That bang on the head six months ago caused hallucinations about moving to MS Prevention or Medical Philosophy (urgh, boring). I’m glad you’ve seen sense.
You have caused a quandary. I was just about to contact Dr Wafa about participating in the Sizomus study. Then you say that “This is why we and others are testing CNS penetrant anti-B-cell strategies (ixazomib, cladribine, BTK inhibitors, etc.)”. Like London buses you wait for ages and three (or more) come along at the same time. Too much choice for my MS brain, but hopefully some of these will deliver and deliver what MSers have always wanted – to tackle progression / increasing disability. Your BAFTA winning performance (best video for an MS trial) about Sizomus has steered me in this direction. Thank you for all the hard work.
Ah, just want to point out if you are not a patient of Prof G, his changing of treatment target would have nothing to do with you at all 🙂
Sid, a personal question so please feel free to ignore. I think that you were treated with alemtuzumab fairly early doors and have reported previously that you are ‘doing well’. Your clearly concerned about the smouldering element of the disease (rightly so) but are you actually experiencing this or do you consider yourself to be one of the lucky ones potentially ‘cured’ by Alemtuzumab? I’m not just being nosy, just i seem to be in a very similar position to the one you were in 15 years ago and i am still hopeful that Alemtuzumab will take care of the smouldering element
Alemtuzumab has been really good for me. I was DX with ‘“quite aggressive MS” and had a run of quite disabling relapses which left damage. 9 months on an interferon didn’t control the relapses well. I got on an Alemtuzumab trial after a lot of badgering by me. No relapses since the first infusion 15 years ago. No new lesions and no signs of active disease. Annual EDSS have been stable. My big regret was not getting Alemtuzumab a year or so earlier. Over the last 18 months I’ve noticed a bit more stiffness in knees / ankles. Bear in mind that my prognosis wasn’t great as I’m male, diagnosed at 40, quite a lot of lesions and not complete recovery from relapses. As my MRIs shows no activity and I’ve had no relapses, I won’t get any more Alemtuzumab (I haven’t asked, but suspect this). I’ve always taken a belt and braces approach, so will be pursuing participation in trials which target smouldering MS. I’m mid 50s and I suspect treatments to address smouldering MS won’t come to market (if the trials are successful) until 5,7,10 years time. The Alemtuzumab trial got me the drug c.5 years before it was licensed. I’m hoping I’ll be lucky with regard to a drug which targets smouldering MS. As Prof G has indicated, really early treatment with Alemtuzumab could potentially shut down the various process underlying MS. Good luck.
Thanks Sid and glad to hear you’re doing well. I am in a similar boat, male, diagnosed at 38, no disabling relapses so far but spinal cord involvement so obviously not great and original incident was 2015 so I have had the disease for a while, even though at the time I was only classes as CIS. My regret is not pursuing a diagnosis of MS back then when Alemtuzumab for first line and I did make a full recovery from that initial incident. However, maybe I wouldn’t have had a second kid if I’d known so that’s how I don’t get too hung up on that one. I saw your post the other day about walking your girls down the aisle….going to Disneyland. I have the exact same thoughts. Here’s hoping Alemtuzumab does the trick n I’m stable too in 15 years time. Plenty of time for combi therapies to emerge but then patients probably said that 15 years ago. Hope you stike lucky with sizomus 👍
Anonymous,
I think you’re in a much better position going forward. When I was DX 17 years ago, MS (RRMS) was regarded as an inflammatory autoimmune disease. The major breakthroughs since my DX are a recognition that MS is one disease (not 4 distinct diseases), that damage is still accruing in the ‘remitting’ phase of so called RRMS, that there are different types of inflammation caused by different immune cells, and that neurodegeneration caused by smouldering MS needs a different approach to tackle it. I suspect that within 10 years we may see patients given a cocktail of therapies to tackle the various elements of the disease and really reduce the risk of permanent damage.
“Over the last 18 months I’ve noticed a bit more stiffness in knees / ankles. ”
Your right to be on guard but big difference between stiffness and spasticity. Spasticity is big problem in spms…you literally
are so stiff you can’t move..be sure to ask your Dr.s if they notice any spasticity in your walk/movements…if not then
you aren’t progressing.
Can i ask another question?
Have you had sars cov 2 vaccine?
Luis,
Received 2nd jab (AZ) last week. I felt a tiny bit groggy the morning after the first jab, but nothing after the second jab.
Thanks for reply
Sizomus is a ixazomib study
I’m just about to start “High Dose” (2) in the UK. Frustrating that I will then be stuck on this “kitchen sink” therapy, with no prospect of modulating dosing or treatment with this and other drugs (3) /(4), despite my appetite.
Hypothetical question, but if one was to have the initial treatment for say, 2 years, could they then stop treatment, wait for disease breakthrough, and then restart? Would the NHS allow that?
Also, is there any data from other countries (Sweden?) that have offered more flexibility in dosing schedules?
Finally , any progress or timescale with the ADIOS study?
Thanks 😁
Sounds like you are on the alternative ADIOS trial…The High Dose trial and then nothing.
Chances of Pfizer sponsoring a study looking at extended dosing window = %0.
Hi Prof G,
I know different hospitals use different dosing strategies when it comes to rituximab. In Norway they use 1000mg initially followed by 500mg every 6 months after this.
I’m not asking for personal advice, but I’m really curious whether this would be considered low-dosing.
Rituximab is about 6x less potent than ocrelizumab gram for gram. So 600mg of ocrelizumab is equivalent to about 3600mg of rituximab. In the high dose ocrelizumab studies, we are testing 600mg vs. 1200mg vs. 1800mg. In rituximab dosing terms this would be 3.6g vs. 7.2g vs. 10.8g.
In summary, 500mg of rituximab may be good enough to stop relapses and MRI activity but probably does little to tackle smouldering MS. This is why Professor Stephen Hauser dropped a bombshell at ECTRIMS in 2015 when he said the majority of his patients who had been on rituximab for 10 years or longer were now secondary progressive. Unfortunately, in MS time is brain and when you lose brain it is irreversible.
This is interesting, i always thought that the failure to prevent transition to SPMS related to CD20 therapies in general. However, this suggests that even with the current dosing schedule of ocrelizumab, the transition could still be delayed / avoided. We do not know this yet of course but the swedish experience seems to be less damning if based on a much lower dose of rituxumab? maybe i am not reading this correctly
Re: “the Swedish experience”
It refers to breakthrough disease activity, which is mainly driven by relapses and new T2 lesions on MRI. It is not driven by disease progression. You need to remember they only started using rituximab nationally from about 2015 when about 50% of their patients were on rituximab; they don’t have much data on EDSS and SPMS yet. Let’s hope they will show that data at some stage.
And their brain volume data.
“You need to remember they only started using rituximab nationally from about 2015 when about 50% of their patients were on rituximab; they don’t have much data on EDSS and SPMS yet. Let’s hope they will show that data at some stage.”
“And their brain volume data.”
Why do you need the data..?
Time is brain and seems painfully obvious it
shows brain atrophy…higher edss..and spms
>Rituximab is about 6x less potent than ocrelizumab gram for gram. So 600mg of ocrelizumab is equivalent to about 3600mg of rituximab.
I wish this was more widely known. There seem to be a lot of people going on rituximab for cost reasons and believing it’s basically the same thing as ocrelizumab.
Maybe better for making covid-19 vaccine response?:-)
Thanks for doing this post. If you can’t can’t convince MD about smouldering MS then good luck with the wider MS community.
How does the dosing of ofatumumab compare to rituximab?
I’m well aware of smouldering MS….and do not think depleting peripheral CD20 B cells is enough, especially once smouldering MS has become clinically apparent.
What would be your theory why Alemtuzumab is showing higher efficacy than CD20 if it doesn’t get into CNS too? Or in your opinion, the data is not comparable for one to draw the conclusion it is more efficacious?
Great post Prof. G! I’d like to ask you: I’ve been on Natalizumab for 5 years and everything is fine at Neda’s level. Would you suggest me switch to Ocrelizumab for steaming multiple sclerosis? Thanks a lot for the answer. (I am 39 years old and for 5 years I have been diagnosed with ms and Natalizumab the only and first drug taken immediately).
FYI, natalizumab is more effective than ocrelizumab (according to brain atrophy data).
Yes, I also read the study.
DO YOU WANT TO BE TREATED WITH LOW-DOSE ANTI-CD20 THERAPY?
First I would try to “clean up” the genitourinary flora.
????????????????????
There is an author who defends the thesis that multiple sclerosis would be caused by a sexually transmitted infection, one that the treatment of more common sexually transmitted urethritis can be done in a monodose system…what would I have to lose?
And who might that author be? I remember a colleague (who shall remain nameless) of ours getting into extremely hot water for penning just such a speculative hypothesis without any thought as to the implications of what was being written.
What are they, please?
Chronic bacterial infections increase herpes viral load, increasing signaling, in addition to increasing Th17 concentration. Th17 produces the demyelinating lesion. Please don’t trust me, look in articles and your own sources.
Chronic bacterial infections, by attacking the epithelia, favor the differentiation of CD4 Th17 lymphocytes in the lamina propria. Mesangial cells in the epithelium produce IL-17a, which exhibits a bactericidal phenotype. Furthermore, chronic bacterial infections, via TLR4/RNA non coding, favors herpes 4 viral replication. In other words, chronic bacterial infection favors the increase in viral load and, consequently, in signaling via HLA. The systemic elevation of Th17, by itself, already reduces the BBB and, when invading the CNS, it produces inflammatory degeneration via IL-17a/specific receptor. Microglia, astrocytes and oligodendrocytes produce an inflammatory environment when stimulated by Th17 via IL-17a.
The vast majority of sexually transmissible urethritis are subclinical and difficult to confirm in the laboratory.
1) IL-17A is associated with the breakdown of the blood-brain barrier in
relapsing-remitting multiple sclerosis
2) The role of TH17 cells in multiple sclerosis: Therapeutic implications
3) Is multiple sclerosis a sexually transmitted infection?
4) Long Non-Coding RNAs: Novel Players in Regulation of Immune Response Upon Herpesvirus Infection
5)Noncoding RNA MaIL1 is an integral component of the TLR4–TRIF pathway
6) The Th17/Treg Cell Balance: A Gut Microbiota-Modulated Story
7) Th1-Th17 Cells Contribute to the Development of Uropathogenic Escherichia coli-Induced Chronic Pelvic Pain
One of the “questions” you pose below:
“3) Is multiple sclerosis a sexually transmitted infection?”
The existence of paediatric MS suggests not…
An excellent argument, however, urethritis can be caused by bacterial infections already in childhood in a non-sexually transmitted way. In children, enterobacteria (E coli) can cause inflammatory urinary infections and therefore urethritis, especially in girls. Multiple sclerosis in childhood is more frequent in girls, as are urethritis, as both have almost the same biological signature, that is, the same interleukins. IL-8 is the interleukin that best characterizes infectious urethritis. But you can argue: where would the rise in Th17/Th1 that produce inflammation, the demyelinating infiltration of the CNS, come from? Answer: from the intestine through contaminated water drink as if it were suitable for consumption. Brother: Don’t rely on filtering, there’s a lot at stake specifically for you. Never drink water from springs, mines, taps, however much the water has been treated it can and certainly get contaminated on the way to your cup. I believe that with the use of dewormers, with the cessation of ingestion of contaminated water, and the use of antibiotics [Edited by MD to remove drug details] for 10 days the disease would stop its progression.
Dont know where to start on this one…..deworming…Emmmmm
Perhaps I missed it but for someone currently taking Ocrevus what dose would be considered high enough for induction therapy. Could you potentially switch to this if you had been on ocrevus for over 2 years?
Depends who you read
The differential dosing effect, based on body size, was found from a post-hoc analysis of the ocrelizumab phase 3 trials. For, example someone who weighs 60kg is getting 10mg/kg of ocrelizumab every 6 months compared to 5mg/kg in someone who weighs 120kg. Both of these patients are likely to be NEIDA (relapse and focal MRI activity free), but the smaller or lighter 60kg patient is less likely to progress. As this was a post-hoc analysis it now needs to be tested and looked for in a larger study. So it is too early to know what the optimal dose is.
Out of interest does this apply to other drugs as they are not given according to your weight but a standard dose.
Big difference between..”less likely to progress”…and will never progress on this treatment. None of the drugs you suggest work as monotherapy..
So a leap to think together they will act as a cure. Do you really think
this could stop progression in ppms…cause you should test it if you do.
In 6 months you’d have an answer…time is brain…stop wasteing it on trials
that don’t give black and white results.
You have to alter the immune system to be able to control EBV/ms unless
there are breakthroughs in drug therapy…You need to go back and read Pender as he shows women have less cd8+ t cells to control EBV….
“The CD8+ T cell deficiency and increased CD4/CD8 ratio in autoimmune diseases are also present in the healthy blood relatives of patients with these diseases [36, 45, 46, 64, 65], indicating that the abnormalities are genetically determined and not secondary to the disease process. Interestingly, females generally have lower proportions and numbers of CD8+ T cells, higher proportions and numbers of CD4+ T cells, and higher CD4/CD8 ratios than males [62, 66–70]. These gender differences appear to be hormonally mediated because oestrogen deficiency substantially increases the proportion and number of CD8+ T cells and decreases the CD4/CD8 ratio, with the ratio directly correlating with the serum oestradiol level [71]. Lower numbers of CD8+ T cells in females might contribute to the higher frequency of autoimmune diseases in females than males. Because the number of CD8+ T cells normally declines with increasing age, particularly through childhood [72], but also through adulthood [62, 70, 73], the primary CD8+ T cell deficiency will be aggravated as each person ages, as occurs in patients with MS “…..hence why ms progresses w/increasing age..those diagnosed at older age have worse prognosis.
Similarly the 6 out of 23 who progressed in hsct HALT ms trial…were all the ones with lower memory cd4/8 t cells …”While none of the treatment effects studied correlated with clinical outcome, patients who remained healthy throughout the 5‐year study had significantly higher absolute numbers of memory CD4 and CD8 T cells in the periphery prior to stem cell transplantation.”…In other words it worked in 100 % of those with higher memory cd4/8 t cells and 0% in those with the least.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543487/
interesting comment on the CD8+ T deficiency.
Makes me wonder about dimethyl fumarate, which severely reduces CD8+ T cells.
How would you look at patients with DMF-induced long-term (i.e. several years) CD8+ T cell suppression?
It does not have to be higher dose ocrelizumab that affects disease progression in this unpublished post hoc analysis. It can simply be that obesity affects disease progression. So losing weight or increasing ocrelizumab dosing?
https://www.ms-uk.org/obesity-worsens-disability-multiple-sclerosis
Is it high dose ocrelizumab or obesity alone that explains the post-hoc data?
Good point
Could be…that higher estrogen levels from extra weight…results in fewer cd8+ t cells
that control EBV…and more progression in ms.
“nterestingly, females generally have lower proportions and numbers of CD8+ T cells, higher proportions and numbers of CD4+ T cells, and higher CD4/CD8 ratios than males [62, 66–70]. These gender differences appear to be hormonally mediated because oestrogen deficiency substantially increases the proportion and number of CD8+ T cells and decreases the CD4/CD8 ratio, with the ratio directly correlating with the serum oestradiol level [71]. Lower numbers of CD8+ T cells in females might contribute to the higher frequency of autoimmune diseases in females than males.”
https://www.hindawi.com/journals/ad/2012/189096/
“Doctors don’t completely understand why extra weight is associated with higher hormone-receptor-positive breast cancer risk. It’s likely that extra body fat increases levels of estrogen and other hormones. Higher hormone levels can increase breast cancer risk.”
https://www.breastcancer.org/research-news/20120530#:~:text=It's%20likely%20that%20extra%20body,weight%20and%20higher%20hormone%20levels.
This terrifies me slightly!
I don’t think you will find may pwMS who want to simply treat relapses knowing that they are probably progressing in the background.
My friend with MS has only ever been on tecfidera. She said her cons told her ocrelizumab is a ‘sledgehammer’ treatment. This made me wonder if I was on too strong a treatment (especially now we know of the high COVID risks). Now that I read this, I wonder if it is not strong enough!
I would absolutely want an extra treatment after induction therapy with anti CD20. To me this sounds ideal as it avoids the infection risks that I struggle to accept on ocrelizumab.
Do other DMTs eg tecfidera also have the background progression of smouldering MS risk?
“Do other DMTs eg tecfidera also have the background progression of smouldering MS risk?”
Yes…they all do.
The only ones that don’t are Alemtuz and hsct…and even then some still progress.
“My friend with MS has only ever been on tecfidera. She said her cons told her ocrelizumab is a ‘sledgehammer’ treatment.”
If the right tool for the job is a sledgehammer…then you use a sledgehammer.
So ProfG wants go after the EBV Sanctuaries and autoreactive B-Cell populations in the CNS by double dosing Ocrevus in the hope that more of these huge Antibodies will somehow get past the Blood Brain Barrier?
What about simply injecting the usual 600mg per LP directly to the spine?
It does work….It is straight back to the blood in 5 minutes
Not sure I understand the question? Do I want to only treat relapses? As a reader of this blog I’m firmly in the camp of getting as close to cure as you can and that means preventing end organ damage, not just treating relapses. Relapses are just a symptom of a malignancy that is shredding hour brain slowly.,