Is there any way I can be treated with rituximab privately?

[Jonathan Edwards]

@Jonathan Edwards, does that mean that the dosing regime used in the studies in Haukeland should not be used as a template for rheumatologists and oncologists after the drug has been approved? How should clinicians tackle this? And what can go wrong if one is treated with the same dosing schedule as used in the studies if the hospital gives Rituximab and other drugs on a weekly basis and is monitored by doctors?

The Haukeland protocol is an extremely intelligent guess at what might be best at this stage. It is a good template in the sense that as long as the person using it has the expertise of Dr Fluge and Dr Mella to adjust according to what happens along the way it is as good as one can hope for. Fluge and Mella actually have the advantage over me in having both oncological and non-oncological experience now. But without their experience the template could easily be used without adequate attention to intercurrent events, like B cell levels, infections, lung problems etc etc.

 

[Jonathan Edwards]

An oncology hospital department should have experience with Rituximab. That's where one could go. I'm not sure what's an acceptable solution for bed bound patients.

Oncologists in general have no understanding of the mode of action of rituximab in autoimmunity. If they are also haematologists then they may have experience with usage in immune thrombocytopenia but even that is rather different from more chronic autoimmune problems. I can see a potential problem in going to an oncology unit that is used to the way rituximab is used in lymphoma. Drs Fluge and Mella had a steep learning curve in shifting to autoimmune usage. They made it quickly because they are intelligent and creative scientists but they are exceptional.

 

[Jonathan Edwards]

I just hope that somebody, somewhere is thinking ahead to 2018. If the Norwegian Phase III trial produces anything close to a 50% response rate and mostly major responders, the demand for treatment is going to go ballistic.

I think that is where the IimE meetings and the EMERG project are laying important ground. And if it becomes clear that rituximab is indicated for a subset of ME there are a large number of rheumatologists with experience with rituximab who are likely to be able to step in. it is just that at the moment they are not including ME in their clinical service because they do not think they have anything to offer.

 

[Jonathan Edwards]

Rituximab was approved for use in RA in about 2007. The rationale for its use in autoimmunity is indeed still not well understood by many physicians. But when there are hundreds of practitioners using a drug and regularly meeting and exchanging experience practical issues tend to get sorted out. The problem for ME is that physicians who might treat it may not have this experience.

 

[Hip]

The fact that nobody is using it in the UK yet, even in a trial, is largely a reflection of the fact that physicians are not confident that they know enough about what they would be doing to justify subjecting patients to the potential risks.

Are these potential risks primarily the adverse events that can occur during rituximab infusion, for which instant medical attention is required in a hospital setting, or is there also the concern of longer term risks (either known or unknown) that may appear months or years down the line?


Also, with subcutaneous formulations of rituximab now available, has anyone considered developing a daily subcutaneous rituximab microdose protocol, such that for example a 500 mg dose of rituximab might be split into 10 subcutaneous injections of 50 mg, to be given daily over a period of 10 days?

Could such a protocol minimize the dangers associated with rituximab adverse events? I am thinking of a setup where the first 50 mg might be given in a hospital setting, and if there were no adverse events, the subsequent injections could be given by a nurse at a GPs surgery, or even by the patient themselves at home.

 

[Jonathan Edwards]

Are these potential risks primarily the adverse events that can occur during rituximab infusion, for which instant medical attention is required in a hospital setting, or is there also the concern of longer term risks (either known or unknown) that may appear months or years down the line?


Also, with subcutaneous formulations of rituximab now available, has anyone considered developing a daily subcutaneous rituximab microdose protocol, such that for example a 500 mg dose of rituximab might be split into 10 subcutaneous injections of 50 mg, to be given daily over a period of 10 days?

Could such a protocol minimize the dangers associated with rituximab adverse events? I am thinking of a setup where the first 50 mg might be given in a hospital setting, and if there were no adverse events, the subsequent injections could be given by a nurse at a GPs surgery, or even by the patient themselves at home.

The adverse events can be immediate or occur later - days, weeks, or years later.

Giving subcutaneous rituximab is completely pointless if you understand what the point of giving rituximab is - the idea is to produce complete B cell depletion as rapidly as possible. At least if you give all the drug in an infusion centre you cover the single period of high risk adequately. If you gave it daily the patient would have to attend the centre every day or be an inpatient. Giving subcutaneously does not alter the range of reactions you can get as far as we know - it just makes it more difficult to know when they might manifest. Adverse reactions appear to have nothing much to do with the dose given - the acute reactions occur with the first few milligrams and the later reactions probably occur however you divide the doses.

I do not mean to be rude but ideas like this based on a misunderstanding of the pharmacodynamics of the treatment are exactly the sort of extra hazard I worry about if people go for private treatment!!! Even the drug companies do not understand how there drug is working so are developing inappropriate ideas like this. Inexperienced physicians are very likely to think they have a clever idea about a better way that is in fact more dangerous. Serious adverse events were much more frequent when the drug was first used because people did not understand what they were doing.

 

[Sasha]

I do not mean to be rude but ideas like this based on a misunderstanding of the pharmacodynamics of the treatment are exactly the sort of extra hazard I worry about if people go for private treatment!!! Even the drug companies do not understand how there drug is working so are developing inappropriate ideas like this. Inexperienced physicians are very likely to think they have a clever idea about a better way that is in fact more dangerous. Serious adverse events were much more frequent when the drug was first used because people did not understand what they were doing.

This is a very helpful discussion because, now that rtx is looking so promising but the horizon for roll-out is frustratingly still several years away - at least three but probably more - we have hundreds of thousands of severely ill, housebound and bedbound patients in pain and isolation and barely making it through the day, desperately in need of treatment. It's completely understandable that people want to jump the gun.

We need good information made public about the risks of rituximab in the hands of inexperienced practitioners - as patients, we're not in a position to understand what those risks are unless someone with Jonathan's level of expertise tells us.

And we need to know what we can do to make sure that there's the clinical capacity to deliver treatment in our own countries when the time comes.

If rituximab - not methotrexate or something - really is going to be the treatment of choice if the Norwegian and other work pans out then we need to be thinking and planning and, if necessary, doing advocacy work on this now, as @Scarecrow says.

The problem will be the same as it is for RA. In the UK rituximab is used reasonably intelligently in RA and things have gone well. In some other European countries it has been used less intelligently and there have been more problems. University hospitals where there are staff with experience in haematology as well as rheumatology are likely to manage well. Private clinics are an unknown.

I think that is where the IimE meetings and the EMERG project are laying important ground. And if it becomes clear that rituximab is indicated for a subset of ME there are a large number of rheumatologists with experience with rituximab who are likely to be able to step in. it is just that at the moment they are not including ME in their clinical service because they do not think they have anything to offer.

Rituximab was approved for use in RA in about 2007. The rationale for its use in autoimmunity is indeed still not well understood by many physicians. But when there are hundreds of practitioners using a drug and regularly meeting and exchanging experience practical issues tend to get sorted out. The problem for ME is that physicians who might treat it may not have this experience.

So you're saying that the sort of people that we see (if we're lucky) such as immunologists and infectious disease specialists won't have rtx experience but that if rtx is proven to be effective, we'll all end up with rheumatologists who know how to use it?

But is there the capacity? If 250,000 UK patients all try to pile in to rheumatology departments when the starting gun goes off, surely there's no chance of us being treated?

I see that the prevalence of RA in the UK is 400,000 - I don't know how many of them get rtx, but the numbers look pretty worrying in terms of clinical capacity.

What should we be doing about this?

 

[SaraEngland]

I jumped the gun. Couldn't wait any longer. I have no life. Waiting to 2021 or something was not an option.

Mabthera:

Day 0: 1000mg
Day 14: 1000mg
3 months: 500mg
6 months: 500mg
9 months: 500mg
12 months: 500mg

Pre medication:

20mg cetirizine and 120mg methylprednisolone (IV) before every infusion. Done at a private hospital. The oncologist has worked with RTX for many years, and has also read everything there is to read about Fluge and Mella's research.

Not sure if this is something for everyone. Perhaps someone would call me a gambler, but I know what I am getting in to. It could go both ways.

 

[Jonathan Edwards]

If rituximab - not methotrexate or something - really is going to be the treatment of choice if the Norwegian and other work pans out then we need to be thinking and planning and, if necessary, doing advocacy work on this now, as @Scarecrow says.

So you're saying that the sort of people that we see (if we're lucky) such as immunologists and infectious disease specialists won't have rtx experience but that if rtx is proven to be effective, we'll all end up with rheumatologists who know how to use it?

But is there the capacity? If 250,000 UK patients all try to pile in to rheumatology departments when the starting gun goes off, surely there's no chance of us being treated?

I see that the prevalence of RA in the UK is 400,000 - I don't know how many of them get rtx, but the numbers look pretty worrying in terms of clinical capacity.

What should we be doing about this?

I think the answer may be to lie low. If the Department of Health see another big cost coming they are more likely to find a way to block it. And we do not yet know that rituximab is effective. I think agitating for service provision for something like this at this stage may well backfire. If it becomes clear that some PWME should be treated with rituximab then the extra capacity needed will not be any different from the sudden jumps in capacity needed for infusion clinics in rheumatology over the last fifteen years.

 

[Scarecrow]

I think the answer may be to lie low. If the Department of Health see another big cost coming they are more likely to find a way to block it. And we do not yet know that rituximab is effective. I think agitating for service provision for something like this at this stage may well backfire. If it becomes clear that some PWME should be treated with rituximab then the extra capacity needed will not be any different from the sudden jumps in capacity needed for infusion clinics in rheumatology over the last fifteen years.

I share your view of the Department of Health but we aren't talking about a novel and very expensive drug that gives marginal improvement over existing treatments. There is no existing treatment for ME/CFS, so if rituximab should be proven effective, to deny all treatment when one is possible could be a human rights issue. The DoH may have the decision taken out of their hands if a legal case is taken to Europe but that would also incur delay. Meanwhile, those who can pay will be accessing treatment privately.

Also the DoH isn't the only administration in the UK that will be taking a decision on rituximab. We have three other chances at a yes. And if one of the four does, I think it will be impossible for the others to resist.

And we do not yet know that rituximab is effective.

Which is a reason not to act hastily and I agree that we should not agitate at this stage but, on the other hand, there is a 'failing to plan is planning to fail' argument. It makes sense to me to be thinking about this now.

 

[A.B.]

I jumped the gun. Couldn't wait any longer. I have no life. Waiting to 2021 or something was not an option.

I hope it works for you. Please keep us updated, with both the good and the bad.

 

[SaraEngland]

I hope it works for you. Please keep us updated, with both the good and the bad.

Will do. Done two infusions. No allergic reaction.

 

[Hip]

I do not mean to be rude but ideas like this based on a misunderstanding of the pharmacodynamics of the treatment are exactly the sort of extra hazard I worry about if people go for private treatment!!! Even the drug companies do not understand how there drug is working so are developing inappropriate ideas like this. Inexperienced physicians are very likely to think they have a clever idea about a better way that is in fact more dangerous. Serious adverse events were much more frequent when the drug was first used because people did not understand what they were doing.

I appreciate your concerns and worries for the safety and risk reduction issues.

It was not my personal idea, though, just something I read might be possible:

In principle, low RTX doses can be self-administered subcutaneously. If subcutaneous administration is safe and effective, it could be more convenient for patients than intravenous treatment and would make fractionated dosing over prolonged periods possible.

Source: Fractionated subcutaneous rituximab is well-tolerated and preserves CD20 expression on tumor cells in patients with chronic lymphocytic leukemia

I am very cautious when trying new drugs and supplements, and alway try a very small test dose first, just in case there are adverse effects. Thus to my naive mind, taking a small initial dose of rituximab first on paper seems like a safer approach, but I admit I know nothing about how rituximab works.

 

[Jonathan Edwards]

I appreciate your concerns and worries for the safety and risk reduction issues.

It was not my personal idea, though, just something I read might be possible:

The way rituximab is useful in chronic lymphatic leukaemia is quite different from in autoimmunity. There is a specific reason for gradual dosage in CLL because large doses cause cytokine storm and there is no particular need to kill all the bad cells at once. In autoimmunity there is no point in going softly softly.

 

[Rebecca2z]

As a person who has had RTX, I would like to say that my doctor who decided to try this on me is at Stanford in the division of immunology and allergy/program in immunology. I was completely bed bound and unable to make the long trips to Stanford for the RTX treatments.

I was allowed to have the RTX at my local hospital (thanks to my local doctor having the moral courage to take this on) My RTX was given at the cancer/infusion center and had to be done at 8 am and done by 4 pm as there had to be certain people on the floor.

There was an oncologist and a special team of nurses on the floor who can handle any bad reactions. The first round of RTX caused my lips and mouth to burn and my throat became tight, the very minute I mentioned these things to the nurse out came the crash cart, oxygen and extra steroids. The RTX was STOPPED IMMEDIATELY ! I am grateful that I had that team in place. ( the next 3 rounds of RTX went very smoothly and I had no issues)

I am still shocked at how well I have responded to the RTX, it has been life changing to say the least. I just can't believe how lucky I am to have had this.

But don't think this is something to go into without having the right team in place. The last thing you want is to be made even sicker. You think you are at a last resort and are desperate to feel better and you think things couldn't be any worse but they can be worse and you could end up with even more suffering.

I would not have done RTX privately, way too many things unknown. So I do caution others to seek out the right kind of medical teams or wait for the research to come in.

As far as being too sick to have RTX, I will say I truly was on deaths door and completely bedridden, so from my perspective a very very sick person can withstand the treatment. Now we still don't know if I am 'safe' as many things can happen even several months after the RTX was given.

I remain hopeful this treatment is found SAFE for others suffering from autoimmune / CFS.

 

[Sidereal]

The last thing you want is to be made even sicker. You think you are at a last resort and are desperate to feel better and you think things couldn't be any worse but they can be worse and you could end up with even more suffering.

Agreed. If there's one thing I've learned from this illness it's that things can always get worse. Sometimes horribly, unimaginably worse.

@Rebecca2z, I'm curious, as part of your illness before RTX, did you struggle with allergies or hypersensitivities to foods, supplements, meds, odours etc.? I ask because many of us here have mast cell activation issues and multiple chemical sensitivity which can make us react to even simple OTC meds so it's hard to imagine ever being able to tolerate RTX or other potential treatments of serious nature.

 

[Daffodil]

why not try antibiotics if you are so desperate? thats what i did and i was close to death, i think. it sure would be safer than rituxan!

 

[deleder2k]

why not try antibiotics if you are so desperate? thats what i did and i was close to death, i think. it sure would be safer than rituxan!

I think because there are no studies that show that antibiotics would help a PWME.

 

[Sallyagerharris]

Rebecca. It is heartening to hear your story and everything crossed that you continue to improve. One of the few silver linings of this journey is learning including how complicated the health field is giving me an appreciation of the work of medical professionals.

Can I ask what level of ability you are now at. I was "lucky" enough to have 40 years of not having ME, although I can now answer why I often felt so unwell. Anyway I then became ill and am now 50. As with others I am now having to learn patience whilst desperate at seeing a life changing medication sort of just beyond reach.

I think we all know how hard this is to live with and it seems cruel to have the carrot close but not yet reachable. It is weird but it seems harder to see change happening and trying to decide the best course of action which seems to be wait. I'm terrified of not being suitable for rituxamib when and if I get it.

I have just got to a not totally bed bound state having taken 8 months to recover from an operation. I'm currently feeling grateful to be on a better level and just frightened of deterioration. I feel I've been generally getting worse over recent years then the operation knocked me further back. Amazing how we can be grateful to be on a slightly better level of ability that would seem horrific to "normal" people.

I as would others will closely follow your progress via your updates. Really hope you continue to improve.

Sally

 

[ghosalb]

The way rituximab is useful in chronic lymphatic leukaemia is quite different from in autoimmunity. There is a specific reason for gradual dosage in CLL because large doses cause cytokine storm and there is no particular need to kill all the bad cells at once. In autoimmunity there is no point in going softly softly.

Prof. Edwards ; what is your opinion about getting this treatment at OMI in California ? Thank you