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

[BurnA]

For RA physicians prescribe rituximab because it has a license. Just like people buy Mercedes cars because they are for sale. In general they do not get involved in weighing up the risks and benefits - they rely on drug company based papers in the literature - which is probably unwise. Having gathered the data myself and talked to other people involved in development I think I probably do have an idea how to weigh risks and benefits in RA but it is not straightforward. I am pretty sure that it is very worthwhile, having seen the details of the data. The situation in ME is quite different. We do not yet have a trial that showed significant difference on a primary outcome measure and even when we do the outcome measures are much more difficult to interpret in ME than in RA.

How critical is identifying potential responders? if this does get a positive result by 2018 then in terms of weighing up risks and benefits for an individual patient whether the overall response is 20% or 50% or whatever, all a patient can do is decide if the risks are worth it because actually the benefits are purely speculative for them unless they know they might respond.
Its hard to see it ever being a straightforward decision without a known response indicator.

 

[Marky90]

The phase II trial showed no significant effect in terms of its primary endpoint. It was only a post-hoc analysis at six months that showed an interesting difference (you cannot have a statistically significant difference post hoc). It all comes down to looking at the patterns in the data and trying to decide if they look like a real effect. My own impression is that they could well be a real effect but I am not certain and nor are the researchers involved.

I think this may be worth repeating: we do not yet know that rituximab is effective. Certainly Drs Fluge and Mella would not want us to assume that.

Sry professor but I`m not quite following you here, did Fluge/Mella not conclude that rtx works significantly for a subset? Looking at the individual data, a handful of patients are apparantly even in complete remission.

Edit: I dont imply that they concluded generally, just in relation to the particular phase 2 study

 

[Jonathan Edwards]

Sry professor but I`m not quite following you here, did Fluge/Mella not conclude that rtx works significantly for a subset? Looking at the individual data, a handful of patients are apparantly even in complete remission.

Edit: I dont imply that they concluded generally, just in relation to the particular phase 2 study

They concluded that it worked for a subset (meaning some of the patients) but they had no indication of what made this subset the responder subset. So for phase 3 they still have to treat at random because they have no way of knowing who will turn out to be in the responder subset. If the autoantibody studies pan out then maybe there will be a way to identify but so far I think we can only identify in retrospect.

 

[BurnA]

Sry professor but I`m not quite following you here, did Fluge/Mella not conclude that rtx works significantly for a subset? Looking at the individual data, a handful of patients are apparantly even in complete remission.

Edit: I dont imply that they concluded generally, just in relation to the particular phase 2 study

If I can add my cents here...
Strictly speaking professor Edwards is correct in everything he said. However, you and I and anyone else is free to interpret or deduce whether we think rtx is effective or not. I for one believe it is and I think the chances of it being coincidence or luck or other factors that resulted in the patient response is extremely unlikely but not 100% certain just yet.

I find it difficult to understand how a >50% response rate in a double blind placebo controlled trial does not indicate efficacy even if the primary endpoint wasn't met.

However nobody can say for certain just yet. Having said that, I would be interested to hear arguments to convince me it isn't effective .

 

[Marky90]

They concluded that it worked for a subset (meaning some of the patients) but they had no indication of what made this subset the responder subset. So for phase 3 they still have to treat at random because they have no way of knowing who will turn out to be in the responder subset. If the autoantibody studies pan out then maybe there will be a way to identify but so far I think we can only identify in retrospect.

Oh ok, I think i misunderstood what you were talking about

 

[Jonathan Edwards]

Oh ok, I think i misunderstood what you were talking about

Actually, my last answer was probably confusing. I thought you were asking about identifying the subset. But maybe you were asking if the Norwegians concluded ANY efficacy. I think one has to stress that they have not concluded anything definitely from this trial. It did look as if there was a higher response rate than placebo. However, this was only true if one looked at the six month endpoint. At the 3 month endpoint if I remember rightly there was no significant difference.

So in response to BurnA about how you can seem to get >50% response without efficacy the answer is very very easily if you cherry pick the time point you take as evidence, simply because people are going up and down in terms of symptoms over time. The reason why I do think this 6 month time point is very suggestive of efficacy is that I would have recommended that time point to Dr Fluge and Mella if they had asked me beforehand. Three months is a bit early to get full response. But that is arguing with hindsight. It is cheating and the Norwegians are very open about the fact that we do not yet have the sort of evidence we need. All one can say of this study is that it deserved a bigger trial to confirm it

 

[Marky90]

Actually, my last answer was probably confusing. I thought you were asking about identifying the subset. But maybe you were asking if the Norwegians concluded ANY efficacy. I think one has to stress that they have not concluded anything definitely from this trial. It did look as if there was a higher response rate than placebo. However, this was only true if one looked at the six month endpoint. At the 3 month endpoint if I remember rightly there was no significant difference.

So in response to BurnA about how you can seem to get >50% response without efficacy the answer is very very easily if you cherry pick the time point you take as evidence, simply because people are going up and down in terms of symptoms over time. The reason why I do think this 6 month time point is very suggestive of efficacy is that I would have recommended that time point to Dr Fluge and Mella if they had asked me beforehand. Three months is a bit early to get full response. But that is arguing with hindsight. It is cheating and the Norwegians are very open about the fact that we do not yet have the sort of evidence we need. All one can say of this study is that it deserved a bigger trial to confirm it

Ah, yes you`re correct, that was my question.

Right, I think I understand. Problem with ME seems to be that people respond differently time-wise, so that being strict with endpoints in the context of scientifc efficancy might not reflect the actual effect rituximab has? Isn*t it a bit harsh to call it cherry-picking with that in mind?

 

[Jonathan Edwards]

Ah, yes you`re correct, that was my question.

Right, I think I understand. Problem with ME seems to be that people respond differently time-wise, so that being strict with endpoints in the context of scientifc efficancy might not reflect the actual effect rituximab has? Isn*t it a bit harsh to call it cherry-picking with that in mind?

It is not that people respond differently time wise. It is that people's symptoms will go up and down for completely irrelevant reasons during a trial so at some point by chance it is quite likely that 60% of people will feel better. So it is very much cherry picking to look for the time point where 60% are better.

ACross the board, most people who get better during trials get better for reasons other than the treatment. That does not apply to trials of hip replacement or something clear cut like that but it applies to most medical trials.

 

[Marky90]

It is not that people respond differently time wise. It is that people's symptoms will go up and down for completely irrelevant reasons during a trial so at some point by chance it is quite likely that 60% of people will feel better. So it is very much cherry picking to look for the time point where 60% are better.

ACross the board, most people who get better during trials get better for reasons other than the treatment. That does not apply to trials of hip replacement or something clear cut like that but it applies to most medical trials.

True. Yeah i get your point, and I agree that is has to be strict. However a point could be made that with ME/CFS a bunch of studies show that very few percent undergo spontaneous recovery, or even much improvement over several years. Point being: remissions and improvements are arguably likely to be due to e.g. rituximab, not chance, in this particular disease.

I must emphasise that I`m all for endpoints, but it seems to me that too much focus on it might cloud genuinly big responses that might be due to treatment in ME.

Then again, this is all being spewed out with the awareness that I*m no expert on scientific method, statistics nor immunology.

 

[BurnA]

It is not that people respond differently time wise. It is that people's symptoms will go up and down for completely irrelevant reasons during a trial so at some point by chance it is quite likely that 60% of people will feel better. So it is very much cherry picking to look for the time point where 60% are better.

ACross the board, most people who get better during trials get better for reasons other than the treatment. That does not apply to trials of hip replacement or something clear cut like that but it applies to most medical trials.

I know this conversation is moot in that we all have to wait for the phase 3 results before we can say anything definite. But, across the board is across the board and therefore wouldn't you expect similar response in placebo group, if the reasons were for other than treatment?

 

[mango]

There are some rumours floating around about a private clinic in Norway (Sandnes or Stavanger?) offering Rituximab treatments for ME patients, using the same protocol as Fluge & Mella. The total price is said to be around 150 000 NOK (approx 16135 USD or 14426 EUR?).

It was mentioned in a Norwegian newspaper recently too:

Privat alternativ
For opplysningens skyld: Dagsavisen Fremtiden fant et privat legesenter i Sandnes som tilbyr Rituximab-behandling til ME-rammede etter Mella og Fluges framgangsmetode og dosering, inkludert overvåking i et døgn og oppfølging.

Fredag ettermiddag var ikke ansvarlig lege tilgjengelig, men ifølge diverse nettforum koster behandlingspakken rundt 150.000 kroner.

http://www.dagsavisenfremtiden.no/lokalt/vil-ha-noen-friske-år-1.401284

 

[Marky90]

There are some rumours floating around about a private clinic in Norway (Sandnes or Stavanger?) offering Rituximab treatments for ME patients, using the same protocol as Fluge & Mella. The total price is said to be around 150 000 NOK (approx 16135 USD or 14426 EUR?).

It was mentioned in a Norwegian newspaper recently too:

It`s correct, I`m travelling there in November

 

[deleder2k]

Looks like they charge roughly 1/3 of what dr. Kogelnik wants...

 

[Thomas]

It`s correct, I`m travelling there in November

That's great! Best of luck. Do you mind sharing what level of illness you are at and main symptoms? Also please let us know how it goes!

 

[Marky90]

That's great! Best of luck. Do you mind sharing what level of illness you are at and main symptoms? Also please let us know how it goes!

Thanks mate! Of course. I guess I fluctuate between mild and moderate.. Main symptom is the mental fatigue that gets worse upon exertion, and which then manifests physically (feeling shaky, weak, out of it etc). There is also the orthostathic intolerance (lightheadedness, strong feeling to sit down) that makes it hard to walk around. Also I*m mildly sensitive to visual stimuli, so e.g. playing a video game or going to the cinema is challenging. And then of course just the general strong fatigue.

I wil certainly keep you posted on how I fare

 

[ScottTriGuy]

Thanks mate! Of course. I guess I fluctuate between mild and moderate.. Main symptom is the mental fatigue that gets worse upon exertion, and which then manifests physically (feeling shaky, weak, out of it etc). There is also the orthostathic intolerance (lightheadedness, strong feeling to sit down) that makes it hard to walk around. Also I*m mildly sensitive to visual stimuli, so e.g. playing a video game or going to the cinema is challenging. And then of course just the general strong fatigue.

I wil certainly keep you posted on how I fare

@Marky90

How did you get 'accepted' into that program? What were the criteria? How long will you have to stay there and will you have to return at any point?

 

[Marky90]

@Marky90

How did you get 'accepted' into that program? What were the criteria? How long will you have to stay there and will you have to return at any point?

Dont know what the criteria is, but you have to be fully evaluated for other diseases, and there can be no contraindications to take the drug. I don*t have to stay there, one travels back and forth to get infusions.

 

[ScottTriGuy]

@Marky90

You must be fairly close to Norway. How many times will you have to visit their clinic? (Trying to figure if its doable from Canada)

 

[Marky90]

@Marky90

You must be fairly close to Norway. How many times will you have to visit their clinic? (Trying to figure if its doable from Canada)

I see!

Yeah I live in Oslo, Norway It will be 7 times. One for the first appointment, and then infusions at start up, 14 days, 3 months, six months, 10 months and 15 months. I guess you could rent a place for the first two infusions, since its only 14 days apart. Hopefully youll get better/cured some time after the third infusion so it wont be such a hassle..

 

[ScottTriGuy]

6 times in a year and a half, that's not too bad - though I am a delicate flower for flying / time change so that would be kind of hard on me - I'll have to do more research, I look forward to your reports.