Six-year follow-up data reveal that ME/CFS patients treated with cyclophosphamide reported greater and more lasting improvements than those treated with rituximab or placebo.
Physician's Weekly
Extracts
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease with unknown etiology, no validated biomarker, and no approved effective treatment. In the past, some ME/CFS patients with cancer have reported that their cancer drug treatment, which included the cytotoxic drug cyclophosphamide or rituximab, unexpectedly had beneficial effects on their ME/CFS symptoms.
These observations suggest that ME/CFS may be associated with an autoimmune pathomechanism involving B cells/plasma cells and antibodies. To explore the long-term course of disease symptoms and possible late side effects of treatment, this study provided six-year follow-up data for patients with ME/CFS enrolled in the two clinical trials RituxME and CycloME. The RituxME follow-up study was conducted between 01.05.2021 to 01.09.2021, six years after inclusion, and the CycloME follow-up study was conducted between 25.10.2022 to 31.01.2023, six to seven years after inclusion.
At six-year follow-up, the percentage of patients with SF-36 PF > 70 was higher for patients treated with cyclophosphamide (44.1%) compared to those treated with rituximab (27.6%) or placebo (20.4%). The percentage of patients with SF-36 PF > 90 (within normal range) was also higher for patients treated with cyclophosphamide (17.6%) compared to those treated with rituximab (8.6%) or placebo (7.4%). Furthermore, a lower percentage of patients treated with cyclophosphamide (5.9%) had worsening symptoms at six years, indicated by a reduction in SF-36 PF of 20 points lower from baseline), compared to those treated with rituximab (10.3%) or placebo (14.8%).
Overall, study results support the hypothesis that ME/CFS may be associated with an autoimmune pathomechanism which may be targetable by immunomodulatory drugs. Despite encouraging results in the CycloME trial, cyclophosphamide should not be used for ME/CFS patients outside of clinical trials until future research is available as it carries toxicity concerns.
MEA Comment
This is a report on the long-term (6 year) follow up of some people with ME/CFS in Norway who have been treated with cyclophosphamide or rituximab.
Cyclophosphamide is a drug that is normally used to treat various types of cancer. It also has powerful anti-inflammatory effects. So, it is sometimes used to treat more severe forms of rheumatoid arthritis and other autoimmune diseases.
Rituximab is another anti-cancer drug that is normally used to treat non Hodgkins Lymphoma and some other types of lymphoma and leukaemia. As many people will recall it was assessed as a treatment for ME/CFS in a large phase 3 clinical trial a few years ago. The trial failed to confirm any benefits.
Overall, these results suggest that there may be a sub-group of people with ME/CFS who respond to cyclophosphamide and despite the negative results from the phase three rituximab clinical trial, there may also be some who respond to this drug.
Cyclophosphamide, because it kills both cancer cells and normal cells, can cause serious use effects. So, while these results are interesting, and may be worthy of further assessment, this is not a drug that should be used outside a research setting in our current state of knowledge – as the authors make very clear.
Dr Charles Shepherd,
Trustee and Hon. Medical Adviser to the ME Association,
Member of the 2018-2021 NICE guideline on ME/CFS committee,
Member of the 2002 Chief Medical Officer's Working Group on ME/CFS
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