Fluge, Øystein, Rekeland, Ingrid G, Lien, Katarina et al. · Annals of internal medicine · 2019 · DOI
Researchers tested whether a drug called rituximab, which reduces B cells (a type of immune cell), could help ME/CFS patients. Over 150 patients received either rituximab infusions or placebo over one year. Unexpectedly, the placebo group actually did slightly better than the treatment group, and neither group showed significant improvement in fatigue or function.
This large, rigorously designed trial contradicts earlier preliminary findings suggesting B-cell depletion benefits and demonstrates that not all immunological abnormalities in ME/CFS translate to therapeutic targets. The negative result helps redirect research toward other pathophysiological mechanisms and prevents unnecessary exposure to an immunosuppressive therapy with potential serious side effects.
This study does not prove that B cells play no role in ME/CFS pathophysiology—it only shows that depleting B cells with rituximab does not improve clinical outcomes in this population. The findings do not rule out benefit in ME/CFS subgroups (e.g., those with specific biomarkers) or rule out other immune mechanisms. It also does not address whether other B-cell-targeting strategies might be effective.
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
Fluge, Øystein, Rekeland, Ingrid G, Lien, Katarina, Thürmer, Hanne, Borchgrevink, Petter C, Schäfer, Christoph, et al. (2019). B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.. Annals of internal medicine. https://doi.org/10.7326/M18-1451
BibTeX
@article{mecfsatlas-fluge-2019-lymphocyte-depletion,
author = {Fluge, Øystein and Rekeland, Ingrid G and Lien, Katarina and Thürmer, Hanne and Borchgrevink, Petter C and Schäfer, Christoph and Sørland, Kari and Aßmus, Jörg and Ktoridou-Valen, Irini and Herder, Ingrid and Gotaas, Merethe E and Kvammen, Øivind and Baranowska, Katarzyna A and Bohnen, Louis M L J and Martinsen, Sissel S and Lonar, Ann E and Solvang, Ann-Elise H and Gya, Arne E S and Bruland, Ove and Risa, Kristin and Alme, Kine and Dahl, Olav and Mella, Olav},
title = {B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.},
journal = {Annals of internal medicine},
year = {2019},
doi = {10.7326/M18-1451},
note = {PubMed: 30934066},
url = {https://www.mecfsatlas.com/evidence/fluge-2019-lymphocyte-depletion},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/fluge-2019-lymphocyte-depletion
Contribute
Private, reviewed by a human. Not a public comment thread.