Rituximab study in norway. An application to The Research Council of Norway

[Sasha]

Yes, that is the simple reality of it. And it does not seem like a long term answer, I agree. But it is where we are in RA and so far it seems to be practical in the medium term. Both Oystein Fluge and I feel that rituximab alone as used now can only be an interim solution, but it has the great advantage that it tells us what we are trying to achieve. And we have patients with RA who have been very happy on rituximab for up to fifteen years - and we do not even get any permanent remissions in RA - they all need retreatments. I guess I would say that if ME is as bad as it looks to me it is for many people then a holding operation that is good for ten years is probably pretty encouraging!

Some people with ME do spontaneously improve and even go into remission. For example, I have CCC/ICC acute viral onset ME and after years bedbound, I went into some years of partial remission during which I was able to work full-time and have a pretty normal life, until I eventually relapsed back to being bedbound/housebound.

Given that, does the outlook for the use of Rituximab in PWME look more promising than for people with RA? Do people with RA every have spontaneous substantial improvement and/or years of substantial remission? I'm wondering if it's possible to "reset" at least some PWME by using Rituximab without the necessity for the treatment being long-term in all cases.

 

[greeneagledown]

@deleder2k -- Here's how I think the timing would play out. The mean response duration for major responders in the open-label study was 2 years. The placebo-controlled trial found that for responders, the response was in full swing around 6 months. So in the future -- assuming this all works out -- for the typical responders, they would get 6 infusions over 15 months, their response would start around 6 months, and their response would last about 2 years, ending about 2.5 years after their very first dose of Rituximab. So those 6 doses over 15 months really would keep the typical responder out of relapse until about 30 months after the very first Rituximab dose. The only question is whether you would immediately repeat the 6-dose cycle at or just before the 30-month mark, avoiding/minimizing a relapse, or whether you'd want to wait until after relapse so that useful antibodies can be replenished.

Maybe the 15 months after the 6th Rituximab dose is enough to let B cells temporarily reappear and replenish the body's useful antibodies. If that's true, it seems like it would be possible to avoid relapses without continuously depriving the person of B cells and antibodies for years. You'd just do 6 doses over 15 months, wait another 15 months, then repeat.

 

[DanME]

If Rituximab is confirmed to be effective in a significant portion of ME/CFS patients, it will be hard to continue labelling this illness as psychosomatic.

Yes, exactly. If the phase III study brings nearly the same success as the previous studies (around 67% and again with some patients, who achieve a full remission), it will be nearly impossible to dismiss the use of Rituximab in ME/CFS and also to dismiss a very real physical and underlying cause. Even if Rituximab is not the final answer, it will help a lot of people to gain a more active and healthier life for a couple of years. And hopefully more researchers will get interested in finding the pathophysiology. Also new trials can start with other promising drugs (e.g. other and stronger Biologicals). And if more research teams bring more light into the final cause of ME/CFS, it will be much easier to control symptoms.

 

[Jonathan Edwards]

Some people with ME do spontaneously improve and even go into remission. For example, I have CCC/ICC acute viral onset ME and after years bedbound, I went into some years of partial remission during which I was able to work full-time and have a pretty normal life, until I eventually relapsed back to being bedbound/housebound.

Given that, does the outlook for the use of Rituximab in PWME look more promising than for people with RA? Do people with RA every have spontaneous substantial improvement and/or years of substantial remission? I'm wondering if it's possible to "reset" at least some PWME by using Rituximab without the necessity for the treatment being long-term in all cases.

Spontaneous remission probably does occur in RA but it not common. I don't think we have waited long enough to see if longer term remissions are achieved in MEs but it is certainly possible. We need to see more cases treated an followed for five years after stopping treatment.

 

[Sasha]

Spontaneous remission probably does occur in RA but it not common. I don't think we have waited long enough to see if longer term remissions are achieved in MEs but it is certainly possible. We need to see more cases treated an followed for five years after stopping treatment.

Do we have any people approaching that from the Norwegian trials? I can't remember when they started or how long anyone will have been off treatment now.

 

[Jonathan Edwards]

Do we have any people approaching that from the Norwegian trials? I can't remember when they started or how long anyone will have been off treatment now.

Not sure. I doubt many that long.

 

[deleder2k]

If someone... say a "friend" were called yesterday and asked to join the study. Would anyone be interested in updates throughout the study?

 

[Sasha]

If someone... say a "friend" were called yesterday and asked to join the study. Would anyone be interested in updates throughout the study?

Congratulations to, erm, your "friend", deleder2k! I wish you - I mean, your "friend" - every success!

 

[deleder2k]

What do you mean @deleder2k ? Of course we would love all updates throughout the study! Are you talking about a specific "friend"?

Read what @Sasha wrote

 

[deleder2k]

Congratulations to, erm, your "friend", deleder2k! I wish you - I mean, your "friend" - every success!

Not 100% yet.. some tests and talks first, but looks pretty good. 2 years of salt water lol

 

[Sasha]

Not 100% yet.. some tests and talks first, but looks pretty good. 2 years of salt water lol

I've got my fingers crossed for you!

 

[deleder2k]

I've got my fingers crossed for you!

Thank you Sasha

 

[NK17]

I've got my fingers and toes crossed for you @deleder2k

 

[Anne]

I compose an informal ME/CFS newsletter in Swedish most months, and in the August issue I published this info about the Norwegian multi-center study (I was in touch with Prof Mella who graciously helped me with the facts):

The Norwegian multicenter Rituximab study begins

The long-awaited Norwegian phase III study of Rituximab as a treatment for ME/CFS is now getting off the ground. The study is led by the oncologists Prof Olav Mella and Dr Øystein Fluge at Haukeland University Hospital in Bergen, Norway. In their previous studies (e g PlosOne 2011) Rituximab has had a positive effect in around 2/3 of the ME/CFS patients receiving the active substance.

This randomized, double-blind, placebo-controlled phase III study will include 152 patients at five units around Norway. The patients need to fulfill the Canadian Consensus Criteria (CCC) and will be filling in The DePaul Symptom Questionnaire (DSQ) with an added question about whether they are more prone to infection after the ME/CFS onset, or less. Extensive testing will be done before the first infusion.Rituximab will be given week 0 and 2, plus after 3, 6, 9 and 12 months. The patients will then be monitored for another 12 months, so 24 months in total.

A very important part of treatment studies of ME/CFS is objective outcome measures. In this study activity will be registered by Sensewear for 7 consecutive days before and after treatment. At two of the participating units the Stevens Protocol, the 2-day exercise test which has been shown to demonstrate metabolic abnormalities in ME/CFS patients, will be performed. Endothelial function/Flow-Mediated Vasodilatation will be measured at two units, and a sub-study on bowel dysfunction will be performed at the Haukeland unit.

No exact date can be predicted for the completion of the study; it will be completed 24 months after the date when patient no 152 has done the initial testing and been given the first infusion. It will be three years or more before any treatment results can be published.

Prof Olav Mella and Dr Øystein Fluge are also conducting other, small studies of potential medical treatments for ME/CFS.

Read more (Norwegian): B-lymfocyttdeplesjon ved bruk av det monoklonale anti-CD20 antistoffet rituximab (Mabthera®) ved myalgisk encefalopati

Studies regarding Rituximab, B cells and autoimmunity in ME/CFS have also been initiated in the UK, thanks to the charity Invest in ME Research. These are being led by Dr Jo Cambridge at University College London, and advisor for these studies is Em Prof Jonathan Edwards. Read more: http://www.ukrituximabtrial.org/IIMEUKRT Summary.htm

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In case you are Scandinavian, here are my newsletters (in Swedish), published on the Swedish ME Association's (RME) web site: http://rme.nu/nyhetsbrev

 

[deleder2k]

Thank you, @Anne. I think the substudy on Flow-Mediated Dilatation is very interesting. They are trying to find out if the severity of the disease correlates with the decrease in blood flow.
After the measurement, they will give the patients sublingual nitroglycerin to open the vessels. After a few minutes they will do a test again, to see if FMD changes or not.

Not sure if I've mentioned it before, but the experience so far is that the most severe sufferers, i.e those who are bedridden respond in a less favourable way to Rituximab. Why this is is unknown at this stage.

 

[Sasha]

Thanks @deleder2k - I really appreciate your keeping us up to date with what's going on at Haukeland!

 

[MeSci]

I took another beta blocker once, Nebivolol 5mg, it lowered my heart rate and stopped the nightmarish palpitations, but over all my OI got worse. So I stopped taking them.

Hi, @DanielBR - I am thinking of trying Nebivolol for hypertension. What is your blood pressure? And did you try a lower dose of Nebivolol as well? You can get 2.5mg tablets. BTW, there is a poll on blood pressure here.

 

[DanME]

Hi, @DanielBR - I am thinking of trying Nebivolol for hypertension. What is your blood pressure? And did you try a lower dose of Nebivolol as well? You can get 2.5mg tablets. BTW, there is a poll on blood pressure here.

Hi, my blood pressure is usually a bit over the normal range. Like 130/90 or if do a lot 140/100. I don't have low blood pressure. I started Nebivolol 2,5 mg again and it works well. My OI is the same, but my tachycardia and my palpitations are completely gone. And my blood pressure decreased to 120/80 or 110/70. 5 mg was definitely too much!

 

[MeSci]

Hi, my blood pressure is usually a bit over the normal range. Like 130/90 or if do a lot 140/100. I don't have low blood pressure. I started Nebivolol 2,5 mg again and it works well. My OI is the same, but my tachycardia and my palpitations are completely gone. And my blood pressure decreased to 120/80 or 110/70. 5 mg was definitely too much!

Thanks very much! It sounds really promising. My bp is very high without meds, but I will still ask my doc to start me on the lowest dosage. Hope he will agree to let me try it.

 

[Anne]

Not sure if I've mentioned it before, but the experience so far is that the most severe sufferers, i.e those who are bedridden respond in a less favourable way to Rituximab. Why this is is unknown at this stage.

@deleder2k : Could you tell us more about this? I heard that Fluge and Mella were planning/conducting a study on the most severely ill. Did they carry that out but the results were not good? Did the severely ill patients not respond or did they get major side effects? Grateful for any info.