Question

I was very disappointed to see that the big clinical trial of Rituximab being carried out in Norway had failed to show any benefit – so it looks as though it may be the end of road for this particular drug. But I noticed in the ME Association statement on the trial results that the Norwegian doctors are carrying out another clinical trial to assess the safety and benefits of a drug called cyclophosphamide. I know someone with arthritis who takes this drug and finds it very useful. But why could it be of use in ME/CFS? And am I right in thinking that it can also has some very unpleasant side-effects?

Answer

The Norwegians have been conducting what is called a phase 2 clinical trial of cyclophosphamide after finding that some of their ME/CFS patients were finding this drug to be helpful. No announcement regarding results has been made so far. Cyclophosphamide is a powerful drug used to suppress an overactive immune system in inflammatory and autoimmune conditions such as SLE/lupus, myositis and vasculitis (an inflammatory muscle and vascular disease) as well as some types of more severe arthritis that have not responded to other treatments.

So, one reason why cyclophosphamide may be of help in ME/ CFS is because some people with ME/CFS appear to have an ongoing overactive immune system response with the production of symptom producing immune system chemicals called cytokines. Cyclophosphamide is also a powerful cytotoxic (anti cancer) drug that is used to treat malignant diseases such as lymphoma. As with Rituximab, this is a drug that has to be regarded as very experimental at the moment. And given the potential to cause serious side-effects, it should only be used in clinical trials and by doctors who are experienced in prescribing this type of medication.

My feeling is that even if the trial results are positive, this is a treatment that is only going to be relevant to a small sub-group of people with ME/CFS. We are also going to need other independent clinical trials showing both safety and efficacy in large numbers of people before any decision is made to use it for treating ME/CFS here in the UK.

More information

• Research: Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study | April 2020

Conclusion: Intravenous cyclophosphamide treatment was feasible for ME/CFS patients and associated with an acceptable toxicity profile. More than half of the patients responded and with prolonged follow-up, a considerable proportion of patients reported ongoing remission. Without a placebo group, clinical response data must be interpreted with caution. We nevertheless believe a future randomized trial is warranted.