Rekeland, Ingrid G, Sørland, Kari, Neteland, Lisbeth Lykke et al. · PloS one · 2024 · DOI
This study followed patients with ME/CFS for six years after they received either rituximab (an antibody treatment), cyclophosphamide (a chemotherapy drug), or placebo in two earlier clinical trials. The researchers tracked how much the patients could do in their daily lives using standard questionnaires. Cyclophosphamide showed the most improvement, with 44% of those patients reaching good functional levels after six years, but the rituximab and placebo groups showed smaller benefits.
This is among the longest follow-up studies of immunomodulatory treatment in ME/CFS, providing evidence that cyclophosphamide may produce sustained functional improvements in a subset of patients. These findings support the hypothesis that an autoimmune mechanism underlies ME/CFS in some patients and justify continued research into safer, targeted immune therapies rather than dismissing immunological approaches.
This study does not prove cyclophosphamide should be used outside research settings—the authors explicitly caution against this due to toxicity risks. It does not establish which patients will benefit from these treatments or why some improve while others do not. The open-label design of the cyclophosphamide trial means placebo effects and observation bias cannot be entirely excluded.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Rekeland, Ingrid G, Sørland, Kari, Neteland, Lisbeth Lykke, Fosså, Alexander, Alme, Kine, Risa, Kristin, et al. (2024). Six-year follow-up of participants in two clinical trials of rituximab or cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.. PloS one. https://doi.org/10.1371/journal.pone.0307484
BibTeX
@article{mecfsatlas-rekeland-2024-six-year,
author = {Rekeland, Ingrid G and Sørland, Kari and Neteland, Lisbeth Lykke and Fosså, Alexander and Alme, Kine and Risa, Kristin and Dahl, Olav and Tronstad, Karl J and Mella, Olav and Fluge, Øystein},
title = {Six-year follow-up of participants in two clinical trials of rituximab or cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.},
journal = {PloS one},
year = {2024},
doi = {10.1371/journal.pone.0307484},
note = {PubMed: 39042627},
url = {https://www.mecfsatlas.com/evidence/rekeland-2024-six-year},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/rekeland-2024-six-year
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