Dosing question: Rituximab for MS

[Doopies]

This has been offered to me as an MS treatment. I have a few questions I was hoping someone could answer:

Is it always given 1000mg day 1, then repeated 2 weeks later at each time you need it?
How do you know when you need a subsequent dose?
Do you feel "more susceptible" to the common cold while on this therapy?
How long have people been treated- months? Years?
Any downsides? Upsides?

Thanks for answering these questions, I'm trying to make a decision on this therapy. Any info is much appreciated.

[Doopies]

Thank you for your story.

Something you said about "pain in certain areas" caught my attention.

I did notice one unusual thing with the infusion- my left side (leg and some in my arm) felt restless & ached during the first hour dog the Ritux. I thought this was strange. My presenting MS symptom was worse in this leg but bilateral lower leg problems.

Do you think this was the Ritux? Phase anyone else experienced this?

I wanted to rub that leg or move it to decrease the discomfort. After an hour it passed with no intervention.

Sometimes when things like this happen (not during infusion) I use heat or pressure or both to distract the aberrant nerve symptoms. My mom made me some rice pack "blankets" to heat and place over spasming muscles. These have been very useful over the years, you just heat and reheat in the microwave.

Maybe I will have them ready next time.

I was just curious if this happened to anyone else (re activation or LLeg symptoms) during infusion.

Thanks!

Ps- I went ahead & paid for this dose myself while waiting on ins co approval...

[karryon55]

I have been on Rituximab 6 years & 8 months. I was originaly prescribed this for my RA but thankfully it helps my MS as well. I would not like to be without my Rituximab because from the first few months of treatment all those years ago I felt different for the first time. I knew it was working & after trying every other DMD available to me at that time it was certainly a blessing. It took time for me though because I was in a wheelchair & slowly learning to use my body again took a lot of persistence.

There have been times where I've had my next round brought closer than 26 weeks because I wasn't doing so well. I'm in Australia & my Rheumatologist prescribes the Rituximab so I'm not having any special blood tests. If I say my RA is not good I can have it sooner occasionally otherwise it is prescribed as per protocol in Oz at 26 weeks & 2 doses of 1000mg on day 1 & day 15.

I am given IVSM / Methylprednisolone, Zyrtec & paracetamol prior to reduce any reactions. In Aust you have to have the IVSM with Rituximab if you have RA anyway but other countries don't administer this. As it's off label for MS this all depends on the doc prescribing it. It's definitely a win win situation for me. My fear is that one day it will stop working for my MS but I will still need it for my RA. The criteria for RA also requires that I have Methotrexate injections.

In regards to side effects I do get some facial flushing, pain in certain areas, shivering (first few hours), headache for first day, insomnia (steroids), metallic taste (steroids) & some asthma. I am not a good example to use because things were handled badly when I first took it under a research unit (it was new back then) & I had anaphylaxis. They forgot the premed & didn't follow the protocol which would have told them to slow down the IV or stop it for a while. I have had anaphylaxis with other drugs as well & with some I had Respiritory arrest. So please don't use me as an example.

A few days to a week after my Rituximab I am feeling terrific. As I said before I'd be lost without my Rituximab. I do have yearly flu vax & 3 yearly pneumonia vax. I also suffer from another autoimmune condition which affects my white blood cells or bone marrow so I am at more risk of catching things. This is not typical & Rituximab is an immunomodulator versus immunosuppressant so in theory it should not lower your immune response.

I personally can't see any down sides to Rituximab. It's convenient with it's dosing & really doesn't impact on my life. I hope this is helpful to you & not confusing as I have the RA as well. :-)

Take Care,

Karry.

[immisceo]

Aw, thanks!

Yes, I'm pleased to say my eyesight returned to my original baseline—as in pretty darn near-sighted! But it's been that way since elementary school. It took longer for it to come back than it did to lose it (which took about a week), but by about three months later it was quite close to where it was, and by a year later it was testing about the same as before the episode.

You hit on something that was definitely going through my mind when I was weighing up whether or not to participate. Among the reasons was I felt the comparative luxury of being overwhelmed with choices when I was diagnosed versus being overwhelmed with nothing but powerlessness against an unpredictable future. And I realised the only reason I or any of us have all of those medication choices is because thousands of unsung patients participated in trials back when there really were no guarantees it was doing anything or that it was at all safe. And I am so grateful that they did.

This isn't to say it's not a MASSIVE headache and disappointment when those medications aren't working for you. I really admire you for jumping through all these hoops to find the best treatment for yourself. I really wish it was an easier process, because we all deserve the resources we need to be proactive in this. So, virtual hugs and support to you. I hope you get good news soon!

[Doopies]

Wow! Thanks for sharing your story.

Did your eyesight fully recover? Losing sight used to be something I worried about, I have some sight issues but can still see well in good light.

I learned recently my neuro participated in CARE MSI for Alemtuzumab/Campath/Lemtrada. He did not put me up for it, maybe because my presentation was bad but more mild than yours. Also maybe bc he always stressed I should have kids (never did).

He works at a large center so I'm sure there were many worthy candidates that didn't get into the trial. I had also failed Rebif (LFTs) and I think that was the comparator arm. Avonex was my therapy.

I think you are right, it is luck & timing. I fell fortunate with most things in my life so if not this, then I was blessed in other ways :). MS did convert me from a type A to type B person, life is better as a B but I don't think I could have switched such a basic human penchant without the harsh teacher MS can be!

I am glad to hear you got it so early. The hope for MS futures is newly diagnosed people getting strong tmt early. I am sure you were in the active arm all along. I was on Avonex at first and had relapses despite 100% compliance and the addition of older oral immune suppressants.

Most of us will be too far along for tmts such as these or remyelination  therapy to help much but you are probably riding that first wave of disease interruption, possible reversal (or time to wait for such an agent) and repair therapies.

No one is ever lucky to have MS but you are in a strong position against the disease. It is inspiring to hear of someone beating this thing, truly history breaking stuff.

Thanks again for sharing your story. I can't tell you how much hope it brings to know someone is blazing a trail to beat this thing. Many future patients who will never know you, will thank you silently for being a guinea pig for them. :)

[immisceo]

The EXTEND study I participate is an extension of the three year Phase 3 study I was on (named DECIDE), so participation is only open to those who completed that study. This is essentially Phase IV - as in, they're getting the last of their data together before they make an official approach to the FDA for approval. http://clinicaltrials.gov/show/NCT01797965

This is all still likely two or more years off. This is why (well, one of the reasons) these drugs are so expensive. From the first pilot studies to arriving in the pharmacy it's easily a ten to fifteen year odyssey for these companies.

The National Institutes of Health has also run some independent (non pharma) research. A participant blagged about it. Her site is no longer active, but it is archived here. http://web.archive.org/web/20130823000112/http://www.mslabrat.com/

I began on DECIDE in early 2011. http://clinicaltrials.gov/ct2/show/NCT01064401
By the time a drug gets to phase three, there is already years of data available to the company, some of which will have been published. I read up on all I could find before deciding it was right for me.

It also means it was a comparison study. I injected myself once a week with something that may or may not have been Avonex, and I visited the trial site (in my case, a local university hospital) once a month to be injected with what may or may not have be DAC HYP (daclizumab high yield process - the specific formulation of the drug). In other words, at all times I was getting *something*, I just didn't know which one.

As I opted for the extension, I will not know which one I was on from 2011-winter 2014 until that is completed as well, neither can I see the many MRIs I've done. Though, if I'd had objective evidence of ongoing, active disease, they are required to tell me so I can make an informed decision whether or not to continue.

But the extension itself is 'unblinded', meaning both I and my medical team know that since this past winter I have been on DAC HYP with 100% certainty. We all think I was on it all along. I never got flu-like symptoms associated with Avonex, and the DACHYP I inject myself with now still has the same little sting it (or the placebo!) always had.

With DAC HYP, I am tested every month for liver function. So far so good! In fact, now that I only pick up my injections quarterly, every month a nurse comes to my home and draws/centrifuges my blood in the living room. It's great!

Participating in this trial represents the whole of my experience with MS medication. I had only just been diagnosed, so I was a pharmacological clean slate. My timeline/symptomatology was quite out of the blue. In late November 2010 I had a multifocal episode consisting on right foot-drop and right internuclear opthalmoplegia. I wound up in the hospital for nine days where they did every test known to man.

When I left, all the i's were dotted and t's crossed for an MS diagnosis bar a second episode. I was still technically CIS. My body duly obliged the first week of January 2011 with left optic neuritis with full vision loss in that eye for a few weeks. From that point, it was all systems go to be screened for trial participation. I had to wait a month because they need your system to be clear of the methylprednisolone infisions I'd had for the optic neuritis.

I've been incredibly stable since then. The odd day of fatigue, the odd day of being a bit less graceful, but no relapses. I do make sure and look after my mental health as well (a pre-existing issue that I'm aware can be exacerbating directly or indirectly by MS), so I'm on venlafaxine and doing CBT for that.

I'm so sorry you're having a difficult time finding a therapy that fits. Who knows where I'll be when I've been diagnosed as long as you have. It's all so unpredictable! I certainly hope your insurance company approves rituximab. It's truly just dumb luck that I stumbled into the study I'm on, and I'm exceedingly grateful to have had the opportunity. So many of us have to get 'creative' to receive the treatment that is our best fit, whether it's participating in studies, going off label, etc.

[Doopies]

Does your treatment, Daclizumab, cause the same result- low CD19 or 20 levels? Maybe they don't enlighten you in the clinical trial.

So you have been on this for 3.5 years? On the active drug (not placebo)?

Can I ask how you were prior to this therapy (symptoms, length of diagnosis, etc) and where you are now?

I was diagnosed in 2003 & have been on therapy since. Most recently I was on Tysabri but cannot take it any longer due to risks. I really began going downhill in the past 3 years & didn't do well on Gilenya- disease break through.

I appreciate your comments. I was not aware of Daclizumab but will see if it is an option I should consider. It was not offered to me.

I am waiting to see if my insurance will cover Rituzimab. I know it will be a battle because they don't like to say yes to anything off label (Aetna).

Thanks!

[kwarendorf]

The issue with Rituxan being used 'off label' is that it can be very hard to get insurance companies to pay for it. And at about $30,000/year it's not cheap :-) I'm luck. My insuance covers it.

The reason MS is not an on label use is likely fiancial. The costs associated with getting approval from the FDA are substantial. The manufacturer does not hink the MS market is big enough to recoup the costs.

Kyle

[immisceo]

I'm on a somewhat related treatment in that it's also a monoclonal antibody, though I give myself a monthly injection instead of get infusions. I'm a card-carrying lab-rat (it's a drug trial, so I literally have a wallet card from the company in case of medical emergency).

So far, so good for me, and I've been on it (daclizumab) 3.5 years now. Regarding being more susceptible to colds, etc. I've not noticed this personally (anecdote alert!), but I do take sensible precautions such as getting the flu vaccine each year.

I think monoclonal antibodies are the 'next generation' (possibly the third if you count orals) of MS treatment and may well become the default treatment in future. Interferons paved the way for us to all have a better prognosis than the 'diagnose and adios' days. But scientific advancement is a moving train, and those of us with a condition at the forefront of medical advancement have the luxury (or headache!) of getting to / having to periodically reassess our satisfaction with our current treatment.

This is the reality until there's a cure, but that's a much better reality than the decades of tumbleweed that faced folks with MS a few decades ago! Rituximab in particular likely gets less discussion simply because it's technically still used off-label.

If it was specifically licensed for MS, it would likely have the same uptake or discussion as Tysabri (another monoclonal antibody). But it seems to inhabit an odd space wherein doctors in the know will prescribe it, knowing it to be effective, but many people will not have heard of it or have the option to choose it. Hopefully, with people such as yourself and Kyle adding to the weight of evidence in support of its use, it will be added to the official roster someday.

[Doopies]

Thanks for your comments. I think I have decide to start Rituximab :)

I guess we all are guinea pigs in this therapy :)

I am surprised this is not discussed more, as it seems like an almost ideal treatment.

[kwarendorf]

Hi -  I have had 2 rounds of Rituxan for MS. The rounds were about 10 months apart. Each round consisted of 2 infusions spaced 2 weeks apart. I have no idea what the dosage was, for each individual infusion or for the whole round. For me it doesn't much matter, as it seems to be doing its job. I had my latest round od CD19 blood work a week ago and gthe numbers are good :-)

Kyle