What is the ME Association doing about Rituximab? Statement 8 July 2013

Yes, SF36v2. I think the questions are the same (or perhaps very small changes) but scoring method different. Population mean of 50, standard deviation (IIRC) of 10.

Isn't that 3 out of 15 treated? The other 15 were on placebo? 20% full remission is considered the best sort of outcome for drugs for rheumatoid arthritis. In practice that tends to pan out to about two thirds of patients being very satisfied with their response. To get this level of response without subgrouping is surprisingly good to my mind. We just need to be sure it is reproducible in other populations.

Yes, that's a good point. I'm just trying to determine what our expectations should be. And I think it's OK to point out that most of us shouldn't expect full remission after treatment with Rituximab. But what can we expect, based on the information available so far? I can't yet work it out, and that's what I'm trying to do.

It's confusing that there are so many threads about Rituximab now, and perhaps I should have posted my concerns and analysis on a thread that isn't related to fundraising? I'll have a look for the original thread re the Fluge and Mella study.

I don't have fixed views on Rituximab, except that I think the research is very important and has the potential to transform our lives. I think it's a reason for cautious optimism, and I absolutely want to see this trial go ahead.

Donations always welcome!

OK, thanks Dolphin. I can't see that information in the paper but I'll have another look.

It was clarified in this comment:

http://www.plosone.org/annotation/listThread.action?root=21433

Ah yes, thank you, I got confused. 15 were in the treatment group. I'll amend my earlier post.

I'm not certain that three patients experienced full remission: I'm basing this on media reports. Others, including yourself, might know more about it.

I'm glad that you think it's a very good outcome. It's helpful to have your professional input about it.

I'm feeling less cautious about it than I did earlier.

Thank for that, Dolphin. I don't think I'd seen those comments before now. (But with my memory, I might have read them in full. Who knows?!?) That does make it much more difficult for me to interpret the results, until I've fully understood the normalised scoring method.

Although to be clear a score of 47 normalised scoring is much, much better than 47 on the scoring used for the PACE Trial (although the 47 only represents a peak).

I need to reread the paper but I think they are quoting the physical health scores which is a summary measure over four subscales which includes the physical function score that PACE uses but also the Role-Physical, Bodily Health and General health subscales.

The mental health scores are also a combination of 4 subscales.

It does worry me that they quote mean differences since I'm not sure that the questionaire structures justify the mean rather than using the median. Depending on how normalisation is done though this may help.

If you are interested in individual patient scores and what happened to the different patients graph
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026358.g003/originalimage
Shows graphs of various responce measures over time for the 10 patients that responded.

All the scores, both the eight subscale scores and the two summary scores, are in Table 4: http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026358.t004/largerimage

I have not done any calculations for myself yet, but I think these are the gold nuggets:

Do keep in mind however that, as SMcGrath later points out, these are peak scores and not endpoints.

The more recent study (so far unpublished) is rumoured to have better results.

Sorry chaps but it's still all Greek to me

Worth bearing in mind that patients relapsed (as I think happens with other autoimmune diseases, where they need a maintenance dose) so a peak score rather than endpoint seems appropriate. Presumably this choice was planned and based on a knowledge of how Rituximab behaves.

Yes, the peak/maximum scores seem appropriate because long-term maintenance doses were not being administered.
I think that the next trial is investigating longer-term maintenance doses, if my memory serves me right.

It seems that I had completely misinterpreted the Norwegian Rituximab trial, because I hadn't studied it in enough detail, and hadn't realised that the SF-36 scores had been normalised. Thanks to Dolphin and biophile for pointing out the details that I needed.

It seems that S McGrath has already done the analysis that I was attempting to do earlier...

To summarise S McGrath's interpretation of average peak improvements for SF-36 PF scores in the treatment group:

Equivalent raw average SF-36 PF scores & improvements in treatment group:
Baseline score 44.9
peak increase as a result of placebo effects 9.2
Maximum score after placebo effects added 54.1
further peak increase after treatment 22.4 (total peak increase for treatment, including placebo effects = 31.6)
Maximum score 76.5

Yes, these seem like respectable average peak improvements. Much better than my original interpretation! Now I better understand the enthusiasm for the research.

And, as T Kindlon points out, the benefits would be more impressive for those who responded to treatment.

I hesitate to interpret the SF-36 physical function (PF) scores further, because I haven't read the study in enough detail, and I might be inappropriately taking them out of context...

But an improvement in (non-normalised) average SF-36 PF scores from 44.9 to a peak of 76.5 seems respectable.
These are average scores, so a number of participants would have better than average peak improvements, and a number of patients would also have peak scores above 76.5.

The SF-36 PF scale is between 0-100, and a score of 100 would be perfect health. Some research papers have used a score of 80 to indicate a 'recovery', but it's not perfect health. Scores above 80 could perhaps be considered to be mild physical impairment.

But these are peak scores (the maximum score that was recorded during the trial), so long-term therapeutic effects are not indicated in these scores. I think the next study will investigate the effectiveness of maintenance doses, and will hopefully report on improvements over the longer term.

Thanks, Bob - looks to me like we need a good summary of this somewhere.

Yes, that would be good, but not by me. I've got a lot of reading to do before I fully understand the paper. And my understanding of the results is based entirely on S McGrath's very helpful analysis of the SF-36 PF scores.

Would be amusing if all or most of the Rituximab group at some point met the PACE Trial criteria for recovery.

Morning,

Someone on Facebook was asking for information about Rituximab last night; and I remembered the following article from Discover magazine back in April. On reading it I realised that Prof. Edwards helped with some of the background and is indeed quoted. Anyway, a little refreshing of what it was all about was in order. Thought you all might like a recap too

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