Research – Rituximab phase 2 trial
In October 2011 Norwegian scientists caused a stir worldwide when they published the results of a phase 2 clinical trial which had accessed the use of a powerful anti-cancer drug known as rituximab in a small group of people with ME/CFS. The results indicate that rituximab could be a treatment for ME/CFS, certainly in a sub-group of people who have a particular form of immune dystunction of part of their illness. At time of writing the results are need of further assessment through more clinical trials before any firm conclusions can be drawn. Nonetheless, it was enough to prompt the Norwegian goverment to award £219,000 to the researchers to see if they could replicate their findings in a larger, open-lable study. And their was an official Norwegian Government apology to people with ME/CFS for not previously taking the illness seriously.
Below you can read a summary of the study published in PlosONE or you can go strait to the full paper here (click to go to PlosONE paper).
Full title: Benefit from B-Lymphocyte Depletion Using the Anti-CD20 Antibody Rituximab in Chronic Fatigue Syndrome. A Double-Blind and Placebo-Controlled Study
Authors: Øystein Fluge1*, Ove Bruland1,2, Kristin Risa1, Anette Storstein3, Einar K. Kristoffersen4, Dipak Sapkota1, Halvor Næss3, Olav Dahl1,5, Harald Nyland3, Olav Mella1,5
1 Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway, 2 Department of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway, 3 Department of Neurology, Haukeland University Hospital, Bergen, Norway, 4 Department of Immunology and Transfusion Medicine, Haukeland University Hospital, and The Gade Institute, University of Bergen, Bergen, Norway, 5 Institute of Internal Medicine, Section of Oncology, University of Bergen, Bergen, Norway
Publication date: 19 October 2011
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.
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.
Read the full paper on PlosONE.