Following is an explanatory news release from PLoS ONE – the journal that published these intriguing research findings on Oct 19; plus a link to the full text article, a summary abstract of the key findings and the ClinicalTrials.gov description of the trial.
PLoS ONE News Release:
Chronic fatigue syndrome (CFS) may be alleviated by the anti-cancer drug Rituximab, suggesting that the source of the disease could lie in the immune system, according to a new study published Oct. 19… Uncertainty about the cause of CFS, which is characterized by extreme, unexplained exhaustion, among other symptoms, has led to much debate, but the authors of this recent study believe they may have found the answer.
The work, led by Drs. Oystein Fluge and Olav Mella of Haukeland University Hospital in Norway, was initiated when the researchers noticed a patient with both chronic fatigue syndrome (CFS) and Hodgkin’s lymphoma who showed marked recovery from CFS symptoms upon treatment with chemotherapy.
The investigators reasoned that the effect could be mediated through B-lymphocyte depletion, and to further investigate this connection they conducted first a pilot case series, and then a double-blind, placebo-controlled phase II trial with 30 CFS patients, and found that the Rituximab treatment was associated with significant, but generally transient, improvement in CFS symptoms.
Rituximab is a B-lymphocyte depleting agent. It acts as an antibody against a protein found primarily on the surface these cells, which are a component of the immune system.
According to the authors, “the delay of clinical responses after the initial and rapid B-cell depletion suggests to us that CFS/ME, which is often preceded by an infection, may be a form of autoimmune disease in which B-cells are important”. Thus, this study reveals a potential new direction for CFS research.
Benefit from B-Lymphocyte Depletion Using the Anti-CD20 Antibody Rituximab in Chronic Fatigue Syndrome. A Double-Blind and Placebo-Controlled Study – Source: PLoS One, online Oct 19, 2011
By Oystein Fluge, Olav Mella, et al.
[Note: the full text of this article is available online at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0026358 – (scroll down).]
Background: Chronic fatigue syndrome (CFS) is a disease of unknown aetiology. Major CFS symptom relief during cancer chemotherapy in a patient with synchronous CFS and lymphoma spurred a pilot study of B-lymphocyte depletion using the anti-CD20 antibody Rituximab, which demonstrated significant clinical response in three CFS patients.
Methods and Findings: In this double-blind, placebo-controlled phase II study (NCT00848692), 30 CFS patients were randomised to either Rituximab 500 mg/m2 or saline, given twice two weeks apart, with follow-up for 12 months. Xenotropic murine leukemia virus-related virus (XMRV) was not detected in any of the patients.
The responses generally affected all CFS symptoms. Major or moderate overall response, defined as lasting improvements in self-reported Fatigue score during follow-up, was seen in 10 out of 15 patients (67%) in the Rituximab group and in two out of 15 patients (13%) in the Placebo group (p = 0.003).
Mean response duration within the follow-up period for the 10 responders to Rituximab was 25 weeks (range 8-44). Four Rituximab patients had clinical response durations past the study period.
General linear models for repeated measures of Fatigue scores during follow-up showed a significant interaction between time and intervention group (p = 0.018 for self-reported, and p = 0.024 for physician-assessed), with differences between the Rituximab and Placebo groups between 6-10 months after intervention. The primary end-point, defined as effect on self-reported Fatigue score 3 months after intervention, was negative.
There were no serious adverse events. Two patients in the Rituximab group with pre-existing psoriasis experienced moderate psoriasis worsening.
Conclusion: The delayed responses starting from 2–7 months after Rituximab treatment, in spite of rapid B-cell depletion, suggests that CFS is an autoimmune disease and may be consistent with the gradual elimination of autoantibodies preceding clinical responses. The present findings will impact future research efforts in CFS.
Trial registration: ClinicalTrials.gov NCT00848692 [See trial description at http://clinicaltrials.gov/ct2/show/NCT00848692]
Source: PLoS One, online Oct 19, 2011. Fluge O, Bruland O, Risa K, Storstein A, Kritoffersen EK, Sapkota D, Naess H, Dahl O, Nyland H, Mella O. Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway; Department of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; Department of Neurology, Haukeland University Hospital, Bergen, Norway; Department of Immunology and Transfusion Medicine, Haukeland University Hospital, and The Gade Institute, University of Bergen, Bergen, Norway; Institute of Internal Medicine, Section of Oncology, University of Bergen, Bergen, Norway.