What degree of change do we want from an effective treatment for ME/CFS?

[Evergreen]

I came across an article about Selma Blair, who has MS (Red magazine, March 2026, p.156-7). She described the change since starting a new treatment:

Having started the drug cladribine a couple of years ago, she’s now relapse-free. Her most recent brain scan brought the best news yet: ‘No evidence of disease activity.

She still lives with dystonia, some mobility issues and, she says, ‘my speech kind of goes in and out’. But the contrast since starting her current treatment is clear. Rating her symptom severity, ‘I’ve probably gone from an eight to a four and a half, which is a huge difference.’

That's what I want from an effective treatment. I want a change in severity.

She has to rest:

‘I have to rest more than you’d think. I might retire to regroup, to meditate and hopefully get a little sleep, or get in the bathtub.’

but she's also able to box and horse-ride (the latter with an ice vest). She competed in Dancing with the Stars.

I don't need to be able to do those things. I relapsed from apparently-completely-recovered after resuming vigorous exercise. I can live without exercise.

But the degree of change she describes would take me from severe to moderate, maybe even the upper end of moderate. That, I want.

What degree of change would get you excited about a treatment?

 

[Evergreen]

Another example, this time from cystic fibrosis. Trikafta/Kaftrio is considered a gamechanger:

Elexacaftor–tezacaftor–ivacaftor, relative to placebo, resulted in a percentage of predicted FEV1 that was 13.8 points higher at 4 weeks and 14.3 points higher through 24 weeks, a rate of pulmonary exacerbations that was 63% lower, a respiratory domain score on the Cystic Fibrosis Questionnaire–Revised (range, 0 to 100, with higher scores indicating a higher patient-reported quality of life with regard to respiratory symptoms; minimum clinically important difference, 4 points) that was 20.2 points higher, and a sweat chloride concentration that was 41.8 mmol per liter lower (P<0.001 for all comparisons).

In pain, a 30% improvement in pain intensity is generally considered good.

I want that kind of improvement in my ability to do stuff.

 

[Trish]

I think going up a severity level, in my case from severe to moderate, with the improved symptoms and increased activity level that would involve. Being able to get up and shower and dress every day, and able to walk to a local park or visit a friend would be fantastic. This is hard to think about because it highlights what I've lost.

In terms of measurements for a clinical trial, I would want it to show on my Fitbit as going from a few hundred steps/arm movements, to at least 3000 a day consistently for at least a year to be regarded as clincally significant.

But personally, I'd take any improvement that enables me to do more if the treatment doesn't have side effects.

 

[Kitty]

I can't imagine being able to walk again, but I'd love that! Being able to go to nature reserves that have some steep or muddy paths would be amazing.

I wouldn't mind if I still had mild ME/CFS and had to rest afterwards—after 50 years I've no memory of what it's like not to have it anyway.

 

[cherrypop]

Id say something that means I have less fear of my body and it's reactions, that dramatically reduces the fear of getting worse and not knowing why because it stabilises it to an extent.

Also the ability to do more would be amazing, I'd love to be able to exercise again but would be more than happy with being able to look after myself well and go on walks I think, maybe even socialise more.

I guess if there was a treatment it shows there's hope of more in future as well which would be amazing.

 

[Evergreen]

I think going up a severity level, in my case from severe to moderate, with the improved symptoms and increased activity level that would involve. Being able to get up and shower and dress every day, and able to walk to a local park or visit a friend would be fantastic. This is hard to think about because it highlights what I've lost.

In terms of measurements for a clinical trial, I would want it to show on my Fitbit as going from a few hundred steps/arm movements, to at least 3000 a day consistently for at least a year to be regarded as clincally significant.

But personally, I'd take any improvement that enables me to do more if the treatment doesn't have side effects.

Oh I'd take any improvement too. So far, I've only gotten no improvement with side effects.

I just find it frustrating to spend so much time looking at these barely statistically significant changes in questionnaire scores, when a truly effective intervention will look so different.

Sorry, yes, I know, this discussion does highlight what we've lost. I'm thinking of it in terms of being clear-eyed about the kind of results we need to see.

As I get older I just have less patience for scrabbling around for scraps.

 

[Evergreen]

I wouldn't mind if I still had mild ME/CFS and had to rest afterwards—after 50 years I've no memory of what it's like not to have it anyway.

Yeah, there's a lot of value with each step down in severity. And being more severe trains you to manage being less severe better!

 

[Felis Catus]

I'm severe and spending the rest of my life as moderate and housebound, having some hobbies and quality of life sounds like heaven!

 

[Evergreen]

Id say something that means I have less fear of my body and it's reactions, that dramatically reduces the fear of getting worse and not knowing why because it stabilises it to an extent.

Also the ability to do more would be amazing, I'd love to be able to exercise again but would be more than happy with being able to look after myself well and go on walks I think, maybe even socialise more.

I guess if there was a treatment it shows there's hope of more in future as well which would be amazing.

I know what you mean. I improved initially and then got worse for 10 years. Oddly enough, getting worse was less pleasant. I remember when improving, things would just get easier every few months, like when you're struggling to get through a sticky door and then suddenly you're through.

Being able to talk with people and see friends like @Trish said would be a change I would value a lot.

 

[Sean]

A substantial reduction in pain, brain fog, PEM, and overall increase in the quantity and quality of activity capacity.

I will also accept a full cure, a grovelling apology from the medical profession, the guilty being held to prompt formal public account, and a couple of million dollars to live out my remaining days in secure modest comfort not endless grinding lifelong poverty.

 

[Evergreen]

I'm severe and spending the rest of my life as moderate and housebound, having some hobbies and quality of life sounds like heaven!

Doesn't it? And I remember well how mild and moderate felt - horrible. But after severe, moderate sounds like a wonderland.

 

[Evergreen]

A substantial reduction in pain, brain fog, PEM, and overall increase in the quantity and quality of activity capacity.

I will also accept a full cure, a grovelling apology from the medical profession, the guilty being held to prompt formal public account, and a couple of million dollars to live out my remaining days in secure modest comfort not endless grinding lifelong poverty.

See, that's what I'm talking about. Let's demand more.

 

[Kitty]

If you asked a different question—how do you imagine a treatment working?—I think I'd envisage something more like my psoriatic arthritis or my cousin's IBD. There are drugs that reduce underlying severity, but there are still periods where it flares and is hard to live with. In between, you get stretches with fewer or no symptoms.

That's probably all wrong, since as far as we know there's no tissue damage in ME/CFS. It's just based on how chronic illness usually looks.

 

[Yann04]

For me i don’t really care that much about symptoms. Like if the drug reduces my symptom load by 80% but doesn’t reduce my PEM threshold. I think I’ll just overdo it and crash a couple times until my symptom load increases back to “baseline”. Atleast that’s my experience with drugs that “mask” symptoms.

Obviously I’d take a cure. But at this point any drug that can make me, tolerate listening to music again, or be able to squat in the shower for 5 minutes without PEM, or be able to spend half the day watching TV, or be able to listen to voices without getting PEM. Any one of those would be absolutely worth it. I know from a non-severe perspective these changes look tiny but at the very severe level I’ll take any crumb I can grab. Because at this point crumbs are life-changing.

 

[Utsikt]

The highest degree possible. But any net benefit is better than nothing.

Increasing my functional capacity would be the most important to me. I can deal with a high symptom burden if I’m allowed to do more.

A treatment would also help prove once and for all the ME/CFS isn’t biopsychosocial/psychosomatic, making it a lot easier to live with it.

 

[Evergreen]

For me i don’t really care that much about symptoms. Like if the drug reduces my symptom load by 80% but doesn’t reduce my PEM threshold.

But at this point any drug that can make me, tolerate listening to music again, or be able to squat in the shower for 5 minutes without PEM, or be able to spend half the day watching TV, or be able to listen to voices without getting PEM.

Increasing my functional capacity would be the most important to me. I can deal with a high symptom burden if I’m allowed to do more.

Agree. It has to increase what we can do. And the only way that happens is if PEM is triggered by fewer activities and/or for a shorter length of time and it doesn't turn into deterioration.

A treatment would also help prove once and for all the ME/CFS isn’t biopsychosocial/psychosomatic, making it a lot easier to live with it.

Yeah, I wish that didn't matter, but it does, because it would/should make so much difference to how we are treated.

 

[EndME]

Agree. It has to increase what we can do. And the only way that happens is if PEM is triggered by fewer activities and/or for a shorter length of time and it doesn't turn into deterioration.

I think treatments that only target certain facets (and I'm not talking about "eat salt" type of stuff) would also already be a great advancement, for example if a treatment got rid of cognitive dysfunction (am I'm not quite sure that all type of cognitive dysfunction is always supposed to be related to triggering PEM).

 

[BrightCandle]

The main thing on this topic from a science point of view is that ME/CFS can vary quite a bit over the course of a study combined with the general bias the standard measurement error that they perceive as the minimal detectable improvement isn't actually correct/validated in ME/CFS. Where in depression a +2 out of 36 might be considered enough it would be within the variance of ME/CFS especially on something like a fatigure scale that includes quite a lot depression questions. This is part of the problem with significance at the moment is no one has measured the baseline for these questionaires when doing no treatment, which is kind of maddening. But then rather than that I wished they just used Funcap and objective measures like steps.

I think personally about 0.5 on funcap or about 10% on bell is about the minimum you can be sure comes from the treatment intervention. Any improvement is welcomed although to really change my life its got to be a full step up in severity, about +1 funcap or 20% bell. but I think the heart of the problem is what is actually a real improvement from treatment and not just positivity bias or factors of the questionaire.

 

[Verity]

I’m moderate maybe bordering on severe, and I would be pretty happy with mild. But honestly I want no PEM. I want to be able to hike and ride horses again.

 

[NelliePledge]

Yes having been undiagnosed mild severity for several years I realise it is very far from normal. but I’d like to think having the experience of being moderate severity and the knowledge of the last 11 years would put me in a place to do a lot better at coping with mild severity than my previous experience of that. Reduced pain and less skewed sleeping patterns would make a big difference to my capacity to do physical and cognitive activity and consequently increase my quality of life.