Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study - 2020 - Rekeland, Mella, Fluge et al

Well not different dosing rates but rather different dosage scheduling. Every 4 weeks the sixth dose is on week 20; every six weeks the sixth dose is on week 30. The total dosage in both cases is the same, about 9 grams.

Every 4 weeks: 0,4,8,12,16,20
Every 6 weeks: 0,6,12,18,24,30

 

@Kitty

can you describe what improvements you’ve had with sulfasalazine?

Thanks

 

Just an improvement in daily function. It's always hard to pin these things down, but other people noticed before I did; one said I seemed to have got new batteries, another whom I met for coffee after a gap of several months said it was great to see me looking so much better.

Of course, some improvement was down to the fact that it reduced the symptoms of the psoriatic arthritis I was taking it for. But that never added much to the fatigue burden, and I'd only had it for a couple of years when I started on the drug. My ME had stopped me doing things a long time before the arthritis began – for instance, I can swim and garden now if I manage my energy, something I'd already been unable to do for more than a decade before my joints started seizing.

I've twice developed neutropenia significant enough for my consultant to take me off the drug, and I begin to feel the difference in my ME after a couple of weeks. They've now just decided to keep an eye on whether the low white cell count actually causes any problems (it doesn't seem to).

It's possible – even likely – that sulfasalazine wouldn't have any effect on other people with ME, or cause adverse reactions because they're sensitive to sulpha drugs. But if it did help some, the 20% improvement in function would be worth having.

I wish I could talk to my rheumatologist about monitoring other ME patients, but it's pointless...she's great on arthritis, but insists ME and fibromyalgia are the same thing.

 

Thanks, interesting. I have one of the HLA risk alleles for psoriasis/psa, but do not have the disease. Maybe I should try sulf?



https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-015-0640-3

 

I would say it is as long as a piece of string. Since we have no idea whether cyclophosphamide is truly effective and no idea how it works if it does all we can say is that the more you give the more toxic it is likely to be and maybe also the more effective but who knows?

The main reason for a gap between cyclo infusions is to allow neutrophils to recover. That takes about two weeks. I don't know why it is given at longer intervals and I suspect nobody else does either.

 

I wouldn't advise it, unless it's researched for ME – and that won't happen unless someone at least starts with an observational study on ME patients prescribed it for other conditions. It carries risks like all drugs, and needs regular blood tests to check liver & kidney function and blood counts.

By the way, no-one else in our family has PsA (I'd never heard of it till I got it). Simply carrying risk alleles probably doesn't mean very much; having the condition may mean that I carry them, but then so did people in my parents', grand-parents' and great-grandparents' generations. That's well over 100 people, but they lived in a small community, knew one another until they died, and no-one remembered a family member with problematic arthritis. I just drew the short straw!

 

Thanks, that’s what I figured.

 

Some correspondence with Bergen...

"There have been no further updates since the cyclophosphamide study was published in April this year (https://www.frontiersin.org/articles/10.3389/fmed.2020.00162/full). I cannot tell you which proportion of the patients are still in remission, as we have no systematic follow-up of the patients beyond what is described in the article. Every time we contact the patients for follow-up, we need to apply for approval from the regional medical ethics committee. The last time we performed such an extended follow-up was at 38-48 months after the start of intervention, as described in the article.

We believe the results of the cyclophosphamide trial strengthen our hypotheses on the involvement of the immune system in ME/CFS, both in terms of symptom mechanisms and as a target for therapeutic interventions. We are working towards further clinical studies on ME/CFS, but we are as yet undecided on whether cyclophosphamide is the best drug candidate available. Placebo control is one challenging issue, as you point out, but our main concern is toxicity. Although there were few drug-related serious adverse events in the trial, risk of infertility remains an issue and many of the patients did suffer unpleasant, if not serious, side-effects. We are in the process of investigating other possible candidates which may affect the immune system in a beneficial way, before we reach a conclusion on the way forward" ....

[Re changes in cognitive score query]

"We asked the patients to complete a self-report form every two weeks, where they indicated improvement, worsening or no change of a long list of symptoms – among these cognitive symptoms including memory problems, concentration problems and reduced ability to think clearly (“brain fog”). The cognitive symptoms were not a part of the study endpoints and we have not performed formal analyses on these questionnaire items, but our impression during clinical follow-up was that changes in cognitive symptoms followed changes in fatigue symptoms. In other words, the patients who were classed as “responders” generally reported improvement in cognitive symptoms as well.

If you wish to follow the ME/CFS research groups for updates and/or new publications, you can find our web page here: https://helse-bergen.no/en/avdeling...ysikk/research-and-development/mecfs-research "

Comments from me:

1) I think it would be better to stick with cyclo, since it worked.

2) It would be nice if they could analyze the cognitive score data, even if not part of the study endpoints.

 

Not directly relevant to ME, but you guys might be interested in this:

https://www.youtube.com/watch?v=bwuM5F7tPCs