E2 ModeratePreliminaryPEM ✓ObservationalPeer-reviewedReviewed
Standard · 3 min

Benefit from B-Lymphocyte Depletion Using the Anti-CD20 Antibody Rituximab in Chronic Fatigue Syndrome

Øystein Fluge, Olav Mella, Ove Bruland et al. · PLoS ONE · 2011 · DOI

Quick Summary

In this pilot RCT, 30 ME/CFS patients received rituximab (a B-cell depleting antibody used in cancer and autoimmune disease) or placebo. Two-thirds of the rituximab group showed clinical improvement, with delayed response patterns consistent with autoimmune disease mechanisms. The placebo group had minimal response.

Why It Matters

This was the first RCT to suggest an immune (autoimmune) mechanism in ME/CFS with a therapeutic signal. The delayed response to B-cell depletion suggested ME/CFS might involve pathological antibodies. It triggered a large Phase III trial.

What This Study Does Not Prove

The Phase III rituximab trial (Fluge et al. 2019) was negative, failing to replicate these results. This pilot study, while historically important, should be interpreted in light of the negative phase III outcome.

Topics

Tags

Method Flag:PEM_DEFINEDSmall SampleNOT_REPLICATEDEXPLORATORYPEM Not DefinedWeak Case DefinitionExploratory Only
Symptom:Fatigue
Biomarker:CytokinesBlood Biomarker

Metadata

DOI
10.1371/journal.pone.0026358
Sample size
30 patients
Control group
Yes
Review status
Editor reviewed
Evidence level
Single-study or moderate support from human research
Last updated
7 April 2026