I have chosen a slide of the results from the open label extension rituximab study for my PACE presentation to my old academic unit on Wednesday. The more I look at it the more I realise that if you want a placebo effect (which Knoop and White said is how CBT works) then rituximab is a darn sight better than CBT. And the phase 3 study shows that plain water is pretty good. What is remarkable is that for a period of three years without let up a good proportion of patients go to zero score on fatigue (the score is actually maximum on the scale but presumably means 'no fatigue').
This is actually pretty surprising and thought provoking. It seems that if you sell your treatment right you can get a substantial proportion of PWME to get well and stay well for three years with no active ingredient.
The problem we have at the moment is that the definition of CCI seems to be very subjective. From what I can gather from the consensus statement the imaging thresholds are not considered diagnositic. They are suggestive in the presence of appropriate clinical signs. So far we have not heard of any PWME having any physical signs. So I am not very reassured by the idea that they only operate where there is CCI.
I absolutely agree that PWME are not impaired in terms of decision making. They seem very on the ball to me. But children are not in a position to decide and children are being sent for this imaging. With potentially sixty or more years to develop secondary complications from cervical fusion a child does not want ill advised cervical surgery. And if Jen is right to say that the surgeons don't really know anything about ME symptoms and it's just another busy day at the office for them I think I have reason to worry.
This may be a little on the side, but since Rituximab and placebo are touched in the discussion here, I might bring it up as well.
Have not read the rituxme study in detail,
later when considerably improved. Maybe complicating things unnecessary, but what I would kindly ask, is if someone who know the facts and details of the study, could say something of how to interpret the results, especially interested in figuring out what the placebo group, if anything, might tell us? We know of the null-result, that rituximab had no significant effect. That’s fine.
But can anyone who actually have knowledge in detail elaborate a little in regard of the placebo results?
This is my concern: the dynamics of the disease is the same. At the same time there will be quite a considerable difference between a “new” patient able to influence PEM and the “old” patients living in or close to constant PEM. So one has to take into consideration that patients are affected differently, depending on how long they been ill, how quick they managed to stabilize and minimize harm and so on. That’s why it is important to be aware of both short and long duration.
But the important thing I would bring up here, is the dynamics of the disease, then thinking of the multi-system nature, the heavy symptom-burden, such. To simplify: it is an harsh disease. It is not “fatigue/tiredness”, not unspecific and unclear.
When the above - if that is a valid argument -
I just don’t understand how ME-patients in general can have significant lasting placebo-responses? Is that the case? Do we know anything about that? I guess I can imagine short spans of placebo but lasting over a longer period of time? I just don’t get it. Just as an opposite theoretical example, I could more easily understand that you could have better possibility of placebo if you had a patient population with only one symptom. That said, I guess one could argue that if you have many symptoms and you experience improvement in one - you could actually call that a placebo effect. On the other hand when it comes to the latter, the important thing is the multi system dynamics. So if you really experience improvement you should theoretically experience improvement overall on all symptoms.
Based on this, my simple assumption is that if you have a large number of placebo in a patient population and/or very significant improvement, you probably don’t have ME-patients at all or maybe only “new” patients. Is that a valid argument? We know of the chaos, all inclusion problems, things like these that influence every study on ME, probably also the multicenter Rituxme-study, but probably less than other studies. But as long as no biomarker there will be bias even in the most well selected patient population.
But that ME-patients, correctly diagnosed CCC should have long lasting placebo-effect with considerable improvement just seems wrong.
What I really would like, if possible, is that someone shortly summarize the data, - what does the data of placebo group actually tell us.
