Rutuxin or Tysabri?

[Myoak]

This is a fascinating thread and I will address why in my next post but first I wanted to address the topic of PML using Rituxan with a couple of quotes...


"Supposedly, there are no cases of PML with rituxan in multiple sclerosis out of ~40,000 exposed patients. In one series, there were 4 total cases in rheumatoid arthritis treated with rituxan out of 129,000 exposed, suggesting risk of ~1/25,000; 1 of these 4 cases was with no biologic and minimal immunosuppressive therapy.

Source: “Rituximab-associated progressive multifocal leukoencephalopathy in rheumatoid arthritis JAMA Neurology, “09/14/2011 Clifford DB et al.

Reply

Dr. Gavin Giovannoni Tuesday, December 16, 2014 10:16:00 am
Thanks for this. I sat on an PML advisory board several years ago and we reviewed all the PML cases linked to rituximab; we didn't find a single case on monotherapy. The one case referred to here on minimal immunosuppressive therapy had been on steroids. The take home message is that the risk of PML on rituximab is very low; the caveat being carryover PML from natalizumab. I think rituximab, and by inference ocrelizumab and other anti-CD20 therapies, will be a relatively safe drugs to transition onto from natalizumab."

http://multiple-sclerosis-research.b...l#comment-form

[Myoak]

This is a very, very interesting thread, especially for pwMS in the USA.
If your neuro is considering Rituxan rather than Ocrevus he/she is absolutely brilliant, IMHO.

Why?

Because Ocrevus and Rituxan are very, very similar. Both are good meds for MS. Ocrevus was developed because the patent ran out on Rituxan. Ocrevus is tweaked Rituxan. Tweaked, primarily to get a new patent and charge at least 10x what Rituxan costs.

Since they are quite similar why do I think Rituxan is better?

Because the dose and the frequency of infusions can be individually tailored. The neuro does not have to give you a set dosage nor does he have to give it to you every six months as with Ocrevus. That fact might save your life if the spike in cancer rates seen during Ocrevus trials turns out to be an actual risk in real world use of Ocrevus. We don’t know, yet. However, we do know that Ocrevus keeps working at least 18 months after the last infusions during trials.
Here is a link proving that statement...

https://www.ebiomedicine.com/article...17)30045-2/pdf

Click the link and look at the chart on page 6. It shows that Ocrevus continued providing protection 18 months after no more infusions were received.

Clearly, Ocrevus every six months could be too much for some people. Especially if the cancer risk plays out. The cells being depleted by Ocrevus are needed to fight off cancer. So, if you over-deplete them, you may put yourself at an increased risk of cancer. Please understand Ocrevus is new so we have to wait to know for sure if there will be an increase of cancer seen using Ocrevus.

To me, it makes sense that it would, although it may take years to prove.

So, what would an excellent clinician do? I think he would give Rituxan only as often as his patient required. That means if there are no new or enhancing lesions or no new significant clinical signs of MS progression then you may not need an infusion every six months. And, if you get infusions you don’t need why put yourself at risk of cancer or any other health issue which may arise from getting more of an immune suppressing medicine than you need to control MS?

IMO, any doctor using Rituxan rather than Ocrevus is on top of all of this and far out in front of it. I envy anyone who has such a doctor.

Most neuros are going to infuse a person with MS with 600mg of Ocrevus every six months, period, end of discussion. That’s what the FDA approved and, by God (my sincere apologies, no offense is intended) 600mg every six months is what you are going to get even if it kills you; and for some it may… if an increased cancer risk is demonstrated infusing Ocrevus every six months.

Yes, I believe Rituxan is a better option than Ocrevus because I believe a neuro can more easily adjust the dosage and frequency with Rituxan. If you achieve NEDA (No Evidence of Disease Activity) with Rituxan your neuro is free NOT to infuse you until and unless you need it.

Its just as likely to achieve NEDA with Ocrevus but the difference is you are going to keep getting it every six months.

With Ocrevus a person with MS will get 600mg every six months no matter if you weigh 90 lbs. or 300 lbs. and regardless of the individual variance in B-cell depletion even though that depletion may be adversely affecting health issues outside of MS.
IMHO, it will be YEARS before this situation is recognized and adjustments made to accommodate it, if ever. Change happens slowly.

I pounded the table in heated discussion with my spouse’s neuro for an entire year before he finally agreed to extend time between doses of Tysabri to reduce PML risk. Based on that experience, I can predict it will be pure hell for any patient trying to alter the dose or frequency of Ocrevus. It is usually futile and can be extremely stressful arguing with a neurologist even when it is your life that is at stake.

IMHO, what makes Rituxan a FAR superior medicine to Ocrevus is that the dose and frequency of infusions can be adjusted individually as required.

If your neurologist is using Rituxan rather than Ocrevus you have an excellent neurologist, IMO.

BTW, one person said their insurance did not approve Rituxan. Wow, insurance ought to compare the cost of those two meds if they want to save a ton of money. Rituxan is far less expensive.

[Marco]

I do rituximab and prefer it to Tysabri and ocrelizumab.

I am jcv+ so I don't see Tysabri as a long term medication for me. I also want nothing to do with the possibility of Tysabri rebound.

Ocrelizumab is new to the market and I would like to see several years of results post-marketing experience before considering it.

For me, rituximab is an easy infusion every 6 months with no realized side effects. I have no intention of going off the medication in the foreseeable future.

[ru4cats]

Myoak,

There is a new topic over in general questions "21 and newly diagnosed" that could use your wisdom. I'm off to see my neuro today or would answer, but right now my "hair is on fire" with the responses so far. I believe your wisdom would go a long way. Wish MS Forum had a relatively easy way to private message someone. I might try later when I have a chance to calm down.

[Myoak]

Hello ru4cats!

I encourage you to add your perspective to that discussion. I wish that young woman could meet you, hear your story, and see the great condition you are in mentally and physically using Tysabri. You definitely should share your experience with her. It helps immensely to hear personal testimony.

Also, I will post my two cents over there later today or tomorrow. I did read through that thread and didn't notice anything that was inappropriate. Everyone speaks from their own experience and perspective; that is understandable.

I do agree with you that more should be said so I will add my voice and I encourage you to do the same. Keep in mind that this is her first post so MS and everything about it is new and kind of scary. I'm sure I have come on too strong with new people in the past and frightened them away by being too forceful in my opinions or presentations, sometimes anyway.

I will add my voice; it was thoughtful of you to ask. Thank You!

Best wishes on the appointment today!

[Myoak]

Marco,

I'm glad you are having wonderful success with rituximab! Most pwMS seem to do very well on it. There is great wisdom in waiting a few years to see how Ocrevus plays out when someone is already using a highly effective DMT.

You mentioned that you are JCV+ so you don't see Tysabri as a long term medication for you. Also, that MS rebound coming off Tysabri is concerning. Those are both solid statements which I fully understand. Today, I'm not going to address the rebound issue although I may in the future.

But I do have to say something about being JCV+ on Tysabri because it may save a life; it may save someone and their family from a needless and horrible tragedy.

I cannot stress often enough nor in enough threads that extending the weeks between doses of Tysabri beyond the standard 4 week infusion saves lives in those who are JCV+. Going 5, 6, 7, or 8 weeks between infusions has cut the number of PML cases to ZERO since late 2013 in those on dose extension.


In the fall of 2015, Ryerson reported no cases of PML in hundreds of Tysabri patients doing extended dosing. She reported zero cases of PML and since then have been no reports of a single case of PML in those who are JCV+ and going 5, 6, 7, or 8 weeks between infusions.

I am going to keep shouting that out until every person on Tysabri knows it. And, their doctors, too.

I simple cannot live in peace knowing that some MSers will get PML, 23% of them will die from PML, and some like the poor, poor dear man who posted here that his wife had not spoken and two years and may never again because she got PML on Tysabri.

There is no justification for anyone JCV+ to be on 4 week dosing!

Quote..."Our prior retrospective work found that extending the dose up to 8 weeks did not negatively affect the medication’s efficacy in a retrospective review of 2,000 patients in 6 MS Centers across the US."

Quote, "Our new study, carried out in collaboration with Biogen and academic partners presented at ACTRIMS in San Diego, CA... adds an important caveat to known PML risk in natalizumab users. According to the comprehensive analysis of TOUCH database, which includes all natalizumab users in the Unites States, the risk of PML is very significantly lower in JCV Antibody positive patients whose natalizumab infusions have been extended from 4 weeks to 5-12 weeks...

QUOTE "… there were no PML cases among 815 patients who met the inclusion criteria as compared to 96 cases noted in standard interval group (comprised of 23,168 patients)."

"The large risk reduction seen with extending natalizumab infusions by just 2 weeks is potentially practice-changing since it could give neurologists an opportunity to prescribe a highly efficacious medication in a safer way."

http://multiple-sclerosis-research.b...sing.html#more

Dear God in Heaven, please make this known to every person on Tysabri and every doctor prescribing it.

[sarabeach123]

Myoak - I've seen your posts in the past about extended dosing of Tysabri and as I am stable on Tysabri but still JCV negative, I am really really interested in doing more research about this. I am nervous to address this idea with my neurologist as he is pretty "old school" and considering I am JCV negative, I'm worried that he might not have any interest in this. Being more informed with legit sources of information will definitely help me with my confidence in speaking to him about it.

The decision for me to start taking any kind of medication was hard enough and I like the idea of limiting the amount of tysabri that is being infused into me! I'll suffer through a headache for days before resorting to taking Advil!

I too wish we had a private message system. I hate to hyjack a thread like this!

As for the original thread, the only input I have is that for me Tysabri has been completely side-effect free!

[Myoak]

I am stable on Tysabri but still JCV negative, I am really really interested in doing more research about this. I am nervous to address this idea with my neurologist as he is pretty "old school" and considering I am JCV negative, I'm worried that he might not have any interest in this.

As for the original thread, the only input I have is that for me Tysabri has been completely side-effect free![/QUOTE]

Hi Sara,

There are a number of people here at MS World who would echo for them, Tysabri has been side-effect free!

Your inclinations are sound... Why take more of a medicine than you need to maintain NEDA?

I know all too well what speaking to a neurologist is like on an issue such as dose extension! You have my deepest empathy.

What I would recommend is... doing what you are... gather info, get familiar with the issue, and then write out your thoughts and reasons on why you would like to extend time between infusions.

I will post some resource links for you in the Tysabri thread and just call it Resources for Dose Extension. It will take a couple of days before I can get to it but I look forward to doing so!

You are completely on the right track! A friend emailed me today ... "I am quite concerned about long-term B-cell depletion in general. It bothers me that they don't really understand the actual mechanism of MS and in some sense are hitting it with a sledgehammer... while I don't fault the doctors, the treatments we are taking have a profound but not always well understood effect on our immune system."

Well said!

Even though you are JCV- at this point, it would not be unusual for you to convert to positive. But even if you do, you can go on dose extension and greatly decrease your risk of developing PML, and if the trend of no cases holds... well, even better.

Lastly, people on Tysabri convert from negative to positive about 10 times faster than the general population according to one study. Therefore, it is logical to believe if you were less saturated with Tysabri, as you would be on dose extension, it is probable that people on Tysabri would convert from negative to positive less frequently. Yes, IMO, you would be less likely to convert to positive. That is only my opinion.

As time goes on data will be mined to find if that is the case, if you want to wait 10 years on it is another matter.

Go with what makes sense to you. You will feel better about yourself and you will live better, too! And likely be a lot healthier!

It's your life, Sara. Not your doctor's. He works for you; you may have to look for a different one. You are Canadian? If so, I don't know how you go about that.

What I can say is that you are on the right track in cutting back on Tysabri and those on Ocrevus and rituximab ought to be aware that cutting back on depleting B-cells is a great idea because under certain unfortunate circumstances (cancer being one) you will need those cells fighting for you.

The less we alter our immune systems with MS under control the better health we will enjoy. I don't believe even old school doctors can question that statement or the reasoning behind it.

Dear Moderators, please edit my previous post, won't you? Thank you! I meant to say

There is NO justification for anyone JCV+ to be on 4 week dosing!

[KoKo]

[I]Dear Moderators, please edit my previous post, won't you? Thank you! I meant to say

There is NO justification for anyone JCV+ to be on 4 week dosing!

Dear Rolly ~ edit done.

[ru4cats]

Thought I'd share my recent 6 month checkin with my neurologist PA.

At the last appointment I had to really work at getting her to approve a move to 6 weeks for my infusions. She was adamant that "6 would be the limit." Of course, I'd been doing so well, I wanted to go for a flexible 6 to 7 week infusion schedule (8 infusions a year; I like round numbers) and arrived loaded with current research. Surprise, surprise, when I mentioned this her response was, "Sure! How about 8 weeks?" Once I picked my face up off the floor, she said she'd heard a neurologist from Houston who thought extending infusions was the bee's knees. Her exact response was, "It's a no-brainer!" Go figure!

[Medina89]

Most neuros are going to infuse a person with MS with 600mg of Ocrevus every six months, period, end of discussion. That’s what the FDA approved and, by God (my sincere apologies, no offense is intended) 600mg every six months is what you are going to get even if it kills you; and for some it may… if an increased cancer risk is demonstrated infusing Ocrevus every six months.

My dr told me about the extended doses in rituxan,he says they start with 2 doses in a year,then 1 in a year ..and watch reactions.most people do really good on it.Since ocrevus is almost identitical to rituxan i really wonder why this is not possible for ocrevus?

[murrayms]

Yeah no...

Most neuros are going to infuse a person with MS with 600mg of Ocrevus every six months, period, end of discussion. That’s what the FDA approved and, by God (my sincere apologies, no offense is intended) 600mg every six months is what you are going to get even if it kills you; and for some it may… if an increased cancer risk is demonstrated infusing Ocrevus every six months.

My dr told me about the extended doses in rituxan,he says they start with 2 doses in a year,then 1 in a year ..and watch reactions.most people do really good on it. Since Ocrevus is almost identical to rituxan i really wonder why this is not possible for ocrevus?

I was on Rituxan, not sure about your doctor but due to the severity I did 4 rounds of 1000 mg separated by 2 weeks, first two then next in 6 months before CD19 was 0% and absolute zero prior to the 5th, then yes like you say I was switched to Ocrevus despite my first line working because it is FDA approved for MS but more than likely too because they get their vig that Rituxan didn't provide because it's old.

[Medina89]

I was on Rituxan, not sure about your doctor but due to the severity I did 4 rounds of 1000 mg separated by 2 weeks, first two then next in 6 months before CD19 was 0% and absolute zero prior to the 5th, then yes like you say I was switched to Ocrevus despite my first line working because it is FDA approved for MS but more than likely too because they get their vig that Rituxan didn't provide because it's old.

Thats the old way...they did research and found its the same result as with 500 mg per 6 months

[Myoak]

Hello,

Such an interesting appointment and post, ru4cats! Wow, neurologists can be so slow to grasp something but when they do its like switching on a light. Boom! Well, of course, infusing every 8 weeks on Tysabri is a “no-brainer”. Dear God, the argument and stress that would have saved me 5 years ago!

The reason it is now a "no brainer" is because PML is de-risked and coverage is still adequate to keep MS at bay. But please keep this in mind… if you go to 8 weeks and you get a new lesion or enhancing old lesion, you would want to go to 7 weeks between infusions. I have a friend who did just that and is now on a 7-week schedule.

Tysabri came back onto the market in early 2006. Some patients went on dose extension in 2013. Tragically, it took 5 years and Ryerson’s research data to finally get the life-saving practice of dose extension widely accepted; at least in those who are JCV+.

I hope Sarabeach and others who are JCV- will not have to play hell with hard-headed neuros to go to a 6-week schedule. A 6-week schedule in those who are JCV- will delay or prevent conversion, I firmly believe. It makes just as much sense to believe that as it does to believe dose extension de-risks for PML… the same principles apply.

Unfortunately, it could easily take 5 more years to collect and analyze data to prove it, just as it did with dose extension so good luck talking to your neuro. You will have to be firm, willing to argue, willing to make your doctor mad… all fun, right? Seriously, I am so, so sorry if that is the sad situation anyone has to face. But I’d rather prepare you for battle than pretend you won’t have one.

Biogen makes money from infusions so Biogen is not going to go along with extending dose in those JCV-. That is the reality… you are fighting Biogen’s push-back. Nothing else can explain why any thinking neuro would not immediately agree to 6-week infusions for even his JCV negative patients, IMO.

Sarabeach, good luck, girl! I know you can and will get this done. If he does not agree to 6-week infusions keep hammering every appointment. YOU ARE RIGHT! That gives you great strength. He would put you on 6-weeks in a heartbeat if you were JCV+ and at the rate of conversion you will get there someday, anyway. He will give in if you keep trying. Its your life. Your will is stronger than his; you will win if you don’t give up! What do they say? Fight like a girl! Women are absolutely tenacious!

Ru4cats! I am happy for the great appointment you had, Chris! And btw, your post to the 21-year-old girl was one of the best I’ve ever read. Well done!

Hello Medina69,

You live in Sweden? I should have said that if you are in the US you are going to get 600mg of Ocrevus every 6 months. Doctors here are extremely reluctant to do anything outside established protocols because they get sued so often. It may be altogether different there. My guess is that your doctors may have more wiggle room and they could adjust dose as needed. I bet so. Sweden was where the dose extension theory originated for Tysabri. Someone mining your national health data noticed lighter weight people got PML more than heavier people. And the theory that Tysabri concentration was less in heavier people to explain it. Turned out to be true… decrease the concentration and MS is still in check and PML is de-risked. Thank you, Sweden,!!!!!!!!

Hello murrayms,

Wow, they really loaded you with rituximab! They must have wanted to really get on top of the situation with MS and I bet it worked, too. If infected B-cells are driving MS and they wiped them out, I bet that largely halted your MS progression. You mentioned your CD19 was near zero. Likely, your CD20 was very low, also. Both of those are types of b-cells.

You were on Rituxan then they switched you to Ocrevus. You will do well on it, also. They both have almost the identical effect in depleting those types of cells.
Off label, and that is how rituximab is being used in MS, it seems as though neuros are more willing or more free to adjust dose and number of infusions.

Why your neuro switched can only be guessed but it could be a liability issue, I suppose, or money. Ocrevus is approved for MS; rituximab is not.

Back to your point about b-cell depletion… what need is there to get an infusion of a b-cell depleter, either Ocrevus or rituximab, if you are already at zero or very, very low? That is exactly what I mean by adjusting the dose and frequency of infusions. Why get more than you need and potentially put yourself at a safety risk? Some people may need a lot to zero out those b-cells but some surely do not. Why suppress your immune system more than necessary if MS is subdued? Remember Tysabri and how dangerous it was to do that.

The best doctors, IMO, will test for depleted b-cells and make adjustments in dose and frequency but I’m afraid most won’t. Too busy seeing patients, I suppose.

We see how many years it took with Tysabri for doctors to stubbornly, finally recognize that too much Tysabri was killing patients and make adjustments in dose and frequency.

One has to wonder if something similar may happen with Ocrevus if the cancer risk plays out. There may be no increased cancer risk with Ocrevus; we have to wait on data! Importantly, Ocrevus has little PML concern so the situation is not nearly the same as with Tysabri.

Ocrevus and rituximab is selective about the b-cells they deplete. We want b-cells for proper immune function... we want depletion to the point of controlling MS but not destroying decent immune function... that is wonderful balance we hope to achieve.

Tysabri seems to have gotten there in achieving that balance.
Of course, Tysabri does not wipe out b-cells; it only prevents them from crossing the blood-brain barrier.

Ocrevus is still too new to achieve such nuance in dose or frequency. That is why, IMO, rituximab is a good option… off-label, in the USA anyway, I think it is easier to adjust than it will be with Ocrevus, Sure, Ocrevus can be adjusted but will they? Likely not. I believe doctors will be as pig-headed with it as they were with Tysabri for years.

Hopefully, doctors are different in Sweden… or perhaps it would be better to say they have more freedom from lawsuits and can practice more freely to accommodate individual patient’s needs.

Best wishes!

[Medina89]

Yes i am from Sweden,i did not know that about Tysabri..great news

I know roche has been in conflict with the neurologists here,but the doctors "won" so to speak,so they keep using rituxan.i got my first dose in april.1000 mg. in october i will get 500 mg