cladribine / leustatin / mavenclad

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cladribine / leustatin / mavenclad

Postby jimmylegs » Thu Oct 18, 2018 8:48 am

ok so i have this new-to-me neuro i've just seen for the second time. she's making the best attempt to date, of convincing me to consider a dmd.
for the first time since rejecting rebif at dx in 06, i am actually paying attention to the literature on a couple of pharma treatment options.
this is not to say i will go ahead, but my reading has been taking a somewhat unusual direction.

so far, i've been looking at ocrevus / ocrelizumab, its mechanism of action, and whether anything else more 'me' has the potential to have the same effect. and me being me, i've landed on papers like this:

Illuminating vitamin D effects on B cells – the multiple sclerosis perspective (2016)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754614/

but still have more reading to do.

i have not yet read up on cladribine / mavenclad but it sounds like another b-cell targeter. the early appeal for that one is the sound of the regimen:

year 1 week 1: pill a day for 5 days, year 1 week 5: pill a day for 5 days. done for year 1.
it's a chemo drug mind you - not as keen on the idea of losing hair but it sounds like a thinning thing, not full on.

i asked about cost to me, costs to the health care system, and the doc said a. don't worry about the health care system and b. for now the company *may* still be offering compassionate rates/freebies to get people on it, and if so then eventually that option will dry up.

i hate the commerce of disease management, and i still lean strongly away from pharma, but think i will at least continue with the lit review.
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Re: cladribine / leustatin / mavenclad

Postby Scott1 » Thu Oct 18, 2018 2:26 pm

Hi,

If you want some heavy duty reading but you will have to buy it as a book try "The Neurobiology of multiple sclerosis" edited by Alireza Minagar. It's volume 79 of the international review of Neurobiology. It takes you up to 2007 but it captures most of the DMD mechanisms. B cells get a good coverage and it will take you through the thinking behind the drugs. It still takes years to commercialize them after that.

What is her argument that sways you the most?

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Re: cladribine / leustatin / mavenclad

Postby Anonymoose » Fri Oct 19, 2018 6:12 pm

Hey jimmy,

I was considering going with Cladribine but wimped out and stuck with Rituxan. It’s still next on my list for now. I suppose it goes w/o saying that I would be psyched to read of someone else trying it before I try it. You go first and I’ll follow in a few years? :D

Good luck w your research and decision making. I know it must be hard to be considering pharma options.

Be well
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Re: cladribine / leustatin / mavenclad

Postby jimmylegs » Sun Oct 21, 2018 8:49 am

@scott thanks for the tip but i don't think i am in the market for heavy duty dmd reading at present! i wouldn't say my neuro has swayed me to trying anything for sure, but she has convinced me to at least look into this cladribine idea. only having to take anything at all, for 2 weeks out of each entire year, sounds decent. i still need to be convinced

@anon what made you shy away from it? if i find anything interesting in the lit i will share.

once i read up on pros and cons, we'll see if i'm still interested :) an early con:

Cladribine Tablets for the First-Line Treatment of Relapsing-Remitting Multiple Sclerosis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal (2018)
https://link.springer.com/article/10.10 ... 018-0718-2
"The Evidence Review Group was concerned that there was insufficient evidence to conclude that cladribine was superior to placebo in delaying disability progression."
take control of your own health
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ask for referrals to preventive health care specialists eg dietitians
don't let suboptimal self care muddy any underlying diagnostic picture!
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Re: cladribine / leustatin / mavenclad

Postby jimmylegs » Sun Oct 21, 2018 9:16 am

Long-term effects of cladribine tablets on MRI activity outcomes in patients with relapsing–remitting multiple sclerosis: the CLARITY Extension study (2018)
http://journals.sagepub.com/doi/abs/10. ... 5617753365

Abstract
Background
The CLARITY and CLARITY Extension studies demonstrated that treatment of relapsing–remitting multiple sclerosis (RRMS) with cladribine tablets (CT) results in significant clinical improvements, compared with placebo. This paper presents the key magnetic resonance imaging (MRI) findings from the CLARITY Extension study.

Methods
Patients who received a cumulative dose of either CT 3.5 or 5.25 mg/kg in CLARITY were rerandomized to either placebo or CT 3.5 mg/kg in CLARITY Extension. Patients from the arm that received placebo in CLARITY were assigned to CT 3.5 mg/kg. MRI assessments were carried out when patients entered CLARITY Extension and after Weeks 24, 48, 72 and 96, and in a supplemental follow-up period.

Results
At CLARITY Extension baseline, patients who received placebo during CLARITY had more T1 gadolinium-enhanced (Gd+) lesions than patients who received CT during CLARITY. These patients, who were then exposed to cladribine 3.5 mg/kg during the extension, experienced a 90.4% relative reduction (median difference −0.33, 97.5% confidence interval −0.33–0.00; p < 0.001) in T1 Gd+ lesions at the end of the extension compared with the end of CLARITY. Overall, the majority of patients in each treatment group remained free from T1 Gd+ lesions throughout CLARITY Extension. However, a small proportion of patients who were treated with cladribine in CLARITY and received placebo in CLARITY Extension showed evidence of increased MRI activity, and this was associated with a prolonged treatment gap between CLARITY and CLARITY Extension.

Conclusion
A 2-year treatment with CT 3.5 mg/kg has a durable effect on MRI outcomes in the majority of patients, an effect that was sustained in patients who were not retreated in the subsequent 2 years after initial treatment.

personally, MRI activity seems to be improved since getting my act together on vit d3 status. the most recent cranial report said one lesion was smaller. the spinal report said they wanted another look, so the neuro is sending me for a follow-up spinal with gadolinium. we shall we what we see.

in the meantime i am halfway through round two of vit d3 50K x 10d. last round only got me from 50 to 90 nmol/l, but should have gotten me up to 100 nmol/l. i didn't want to do any more on round 1 because in the past my levels went up by 150 when i was only expecting 50. with this 90 result, it's possible i didn't allow enough lag time between end of megadose and the bloodwork. also though, my high test d3 liquid is 8 yrs old so who knows. at least it still works! :)
take control of your own health
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ask for referrals to preventive health care specialists eg dietitians
don't let suboptimal self care muddy any underlying diagnostic picture!
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Re: cladribine / leustatin / mavenclad

Postby Anonymoose » Sun Oct 21, 2018 2:04 pm

Cladribine would be significantly riskier than heavy duty iv/it Rituxan every 4-5 years. It’s impact on the immune system is stronger and lasts significantly longer. That said, I’m not sure my rituxan regimen is working...mri was okay but my increase in OCBs not pleasing in the least.

Cladribine treatment carries infection risks that sometimes aren’t very manageable due to long term lymphopenia. I don’t know how this fits w MS and EBV, but Cladribine treatment is associated w subsequent ebv related cancer similar to post transplant lymphoproliferative disorder. EBV gone wild. Based on the 10 year study Bart’s just posted, I guess that wasn’t a problem for participants. But still ?????

BartsMS posted OCBs are disappearing w Cladribine though...so that’s interesting. Tysabri is the only other dmd that might cause OCB ghosting. Makes me wonder if OCBs really are indicative of impending doom as “they” proclaim. (Like they proclaimed BBB kept the immune system out of the CNS lol) Maybe they’re just red herrings or like those ugly rings you get on your furniture when you forget to use a coaster...an annoying but harmless record of what may even be superficial damage. Tysabri rebound bugs me. My gut tells me tysabri just keeps part of the MS process from happening but allows at least step 1 of the neurodegeneration to happen. So when the immune system is let loose again, it just has a big mess to attack and clean up...rebound.

I’m still considering Cladribine as there isn’t anything else I’d try instead of rituxan now. Hopefully I can hold out for some new miracle treatment to come out or maybe I’ll be abducted and cured by friendly aliens. Either could happen. :P
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Re: cladribine / leustatin / mavenclad

Postby Scott1 » Sun Oct 21, 2018 10:31 pm

Hi Anonymoose,

If its EBV you're trying to control, have you tried valacyclovir recently? It seems to work for me. The drugs your talking about target the inflammatory process rather than the EBV. The valacyclovir is the other way around as it puts a stop in the codon of the RNA ribbon of the EBV so it doesn't make fresh copies. It doesn't touch the immune system itself.

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Re: cladribine / leustatin / mavenclad

Postby jimmylegs » Mon Oct 22, 2018 4:29 am

aside: i trounced a close family friend's chronic eb viral load with nutritional boot camp. this particular close friend also has covert spina bifida, which was diagnosed years later.. family doesn't have the best track record nutritionally.

will get back on track next post :)
take control of your own health
pursue optimal self care at least as actively as a diagnosis
ask for referrals to preventive health care specialists eg dietitians
don't let suboptimal self care muddy any underlying diagnostic picture!
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Re: cladribine / leustatin / mavenclad

Postby Anonymoose » Mon Oct 22, 2018 6:11 am

Hi Scott,

I can’t do the valtrex this time. It makes me too sick and I need my wits about me atm. On the bright side, no valtrex means I can take 2000iu d3/day which should help the Rituxan do its work and seems to be needed as it was the only thing that cleared the long lingering cloud out of my head yesterday.

@jimmy

Yeah, I remember your wisdom worked to kick some ebv butt. I can’t really hard core mess w supplements now either. Don’t tell anyone but I’m losing faith in this ebv-ms thing too. The “thing” that now tickles the back of my mind is that the initial neurodegeneration is driven by some sort of deficiency in components required to maintain your brain (vitamin, mineral, amino acid, enzyme, etc). I’ve not explored the thought further because I know the answer isn’t out there anyway...unless I want to drown in the mind your mitochondria religion and gross diet. Lol.

Anywho...get this back to you. Aside from stubborness (which I too passionately embrace) what’s keeping you from trying a little help from pharma?
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Re: cladribine / leustatin / mavenclad

Postby Scott1 » Mon Oct 22, 2018 2:40 pm

Hi 'Moose,

You took Rituxumab to try to ablate the B cells and EBV needs B cells to persist. Do you think you did that or just gave them a hammering and gain a respite in that time?
I remember a few people tried Valtrex when I suggested it helped me and also didn't like the reaction. It always made me wonder what the differences were. The only common thread I could pick up was most were using D3 at the same time. I never have used D3 because I get plenty of sun on my skin and try to let nature do its thing.
What do you take/use on a daily basis now? We were both targeting a similar thing at the same time but doing it different ways. There may be a lesson in the variations.

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Re: cladribine / leustatin / mavenclad

Postby Anonymoose » Tue Oct 23, 2018 1:49 pm

@Scott1

I guess my original intent was to reduce ebv load and I probably did that. But...ebv can hang out in non-b-cells so I doubt I totally killed it off. Part of the reason I did the beuhner protocol and worked w an out-there integrated medicine doctor was to maximize my immune system’s potential to fight off remaining ebv. All that said, I’ve got no labs to measure ebv load, no way to test if my cd8+ tcell response to ebv improves, no way to prove or reason anything about my treatment with any degree of certainty. Post-Rituxan, I did relatively well for a few years but that might have happened anyway.

I don’t feel like ebv is at the heart of the problem anymore...just like the immune system isn’t at the heart. Answers probably are in variations. Variations in people’s lives and labs. We probably need a whole bunch of us w early RRMS (not me anymore) to live in an institution, with multiple subgroups eating and doing everything alike in the same environments so we can study why people relapse when they do...and why do some relapse more...and why do some recover while others don’t. The answers are likely staring us all in the face but there is no way to see it without observing in a totally controlled environment with single changing variables and loads and loads of labs and tests.

I don’t have anything special going on w regimen now. I take a multi, b complex, b-1, 200 mag glycinate 2x/day, 2000iu d3. I also drink coconut water for potassium. I think the Rituxan is doing it’s thing because I’m extra fatigued (but not basically bedridden and sick like last time). I’m eating a lot of red meat to keep my iron levels up. That’s about it.

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Re: cladribine / leustatin / mavenclad

Postby jimmylegs » Tue Oct 23, 2018 2:34 pm

Aside from stubborness (which I too passionately embrace) what’s keeping you from trying a little help from pharma?


to date, mostly that in spite of some permanent damage and limitations, during 12 years i have had zero relapses or worsening of symptoms related to anything other than nutrient deficiencies and learning curve while figuring out how to correct and balance.

this year's decline is associated with the experience of and aftermath from a severe infection which rounded out three years of neglecting self care in favour of work. every nutrient i finally got around to having tested, was in the dumper. only vitamin d3 was red flagged by the lab, but i know what sized grain of salt goes with any result from a neighbourhood facility.

mri done after this year's infection was bad, and since getting my act together it's better. nothing new, nothing larger, one smaller. one question mark in the spine still pending another look w gadolinium.

other than getting my act together, the other piece holding me back is that i need to understand and have confidence in the evidence base before i agree to support the disease management industry.

also, once again some of my experience this year has been less than impressive where the docs are concerned. when my vision went squirrelly, nobody had anything to offer. the answer was *nowhere* in the ms literature. it's pretty much the luck of the draw re my university's journal subscriptions, that i had access to the physio paper that sorted me out. i have no idea if my vision would be back by now on its own, but i know for sure that the physio didnt work for three days, that it started to work immediately after a individual modification, *and* that it has since helped at least one tims member who was also given no solutions for double vision, by their own eye care professional.

if there was a product that could replace my dead nerve roots and restore proper sensory in my hands, that would be cool. but i am not desperate over it or anything. end rant lol
take control of your own health
pursue optimal self care at least as actively as a diagnosis
ask for referrals to preventive health care specialists eg dietitians
don't let suboptimal self care muddy any underlying diagnostic picture!
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Re: cladribine / leustatin / mavenclad

Postby Anonymoose » Tue Oct 23, 2018 7:01 pm

@jimmy

Fair enough and yeah, I feel that. Good thing we’ve got ourselves. ;)

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Re: cladribine / leustatin / mavenclad

Postby Scott1 » Wed Oct 24, 2018 2:31 pm

Hi,

It looks like we are following quite different protocols.

My day looks like this

Morning
1 large magnesium tablet
2x 500mg Valacyclovir (anti EBV)
2x 500 mg aceytl-l-carnitine (transport fatty acids into the mitochondria)
1x 30mg curcumin (shifts the immune response from Th1 to Th2 mediated - like some of the drugs are supposed to do)
1x900mg N-aceytl-cysteine (precursor to glutathione and all round good guy)
1x 25mg Dantrium (very potent anti spasticity drug. Without it I'm very stiff)

In the evening I repeat and add 5x150mg CoQ10. The aceytl-l-carnitine is synergistic with this and together they promote a healthy electron transport chain and consequently improve mitochondrial health. I have absolutely no problem making energy using these two together whereas I used to be very fatigued and suffered a lot of brain fog. I think the Valacyclovir also helps by blocking EBV replication.

My view, for a long time now, is superoxide generated by EBV infected B cells combines with excessive Nitric Oxide create by too much iNOS generated by inflammation to make peroxynitrite which a major oxidant. Prof Martin Hall developed a theory called the NO/ONOO cycle that makes perfect sense to me. Apart from the Dantrium, everything I take is targeting that cycle.

I make breakfast the major "feast" of the day.

1 probiotic tablet with many strains
1 small glass of apple juice
1 banana (for potassium)
2 boiled eggs (no toast) (for just about everything )
1 avocado (fatty acids, potassium, fibre)

I fill the hole in the avocado with fresh pomegranate seeds (https://www.bbcgoodfood.com/howto/guide ... omegranate )

At lunch, I eat very modestly and in the evening I eat meat and vegetables.

I go out of my way to avoid added sugar and gluten .

Pilates is 3x 1 hour a week, massage is 1 hour per week and dry needling (to break up tight fascia) is about once a month these days.

I actually don't touch D3. Whilst I understand the arguments I don't understand the full cycle well enough and prefer to walk in the sun to start the process.

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Re: cladribine / leustatin / mavenclad

Postby jimmylegs » Thu Oct 25, 2018 4:37 am

lately this is me atm:

just before breakfast, water, 200mg magnesium glycinate, 1 out of a 3 a day active women's multi.

with breakfast , high test vitamin d3 - am on final days of a 50K x 10 day boost. based on the previous boost only getting levels to 90 nmol/l

through the rest of the day
daily:
-one more of the 3 a day multi
-1 super fish oil

every other day:
-zinc 30ng and vit a 10K iu
-vit c 1g and vit e8 complex 400 IU
-another mag glycinate 200 IU

food tends to be oats and berries at breakfast
trail mix for morning snack
sandwich, soup or salad for lunch
appetizer soup or salad for late pm snack
protein and mixed veg for dinner
not into dessert

had dinner last eve w my friend, her son, and her mom. we made tabbouli salad (parsley, mint, quinoa, onion, tomato, cucumber, olive oil, lemon juice, garlic, salt and pep) and burgers (75% grass fed beef, 25% venison, spinach, garlic, feta) on a thin multi grain bun, with onion tomato and kale for toppings.

we made 16 quarter pounders and she put a bunch in the freezer for easy meals later. her docs have advised beef to help her recover from impending radical mastectomy. we're assuming zinc is driving that to some extent, hence the added venison fraction.

we had visited a naturopathic doc specializing in oncology earlier in the day. i'm still trying to vet his qualifications and his supp recommendations. re diet, he had prescribed 10 servings of greens per day, so the tabbouli sets her up for some of that - for the next day or two anyway! plus i dug her greens powder out of the cupboard and we had a serving each in herbal tea. i left the jar on the counter so it doesn't get ignored :)
take control of your own health
pursue optimal self care at least as actively as a diagnosis
ask for referrals to preventive health care specialists eg dietitians
don't let suboptimal self care muddy any underlying diagnostic picture!
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