title: Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study.
abstract: 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.
  
  
  RESULTS
  In this double-blind, placebo-controlled phase II study (NCT00848692), 30 CFS patients were randomised to either Rituximab 500 mg/m(2) 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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00848692.
authors: Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway. oystein.fluge@gmail.com
authors: Øystein
authors: Ø
authors: Fluge
authors: Ove
authors: O
authors: Bruland
authors: Kristin
authors: K
authors: Risa
authors: Anette
authors: A
authors: Storstein
authors: Einar K
authors: EK
authors: Kristoffersen
authors: Dipak
authors: D
authors: Sapkota
authors: Halvor
authors: H
authors: Næss
authors: Olav
authors: O
authors: Dahl
authors: Harald
authors: H
authors: Nyland
authors: Olav
authors: O
authors: Mella
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004311:Double-Blind Method; D015673:Fatigue Syndrome, Chronic / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016133:Polymerase Chain Reaction; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D010919:Placebos; D000069283:Rituximab