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20-10-2011 | Internal medicine | Article

Chronic fatigue syndrome may be an autoimmune condition

Abstract

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MedWire News: B-lymphocyte depletion with the monoclonal anti-CD20 antibody rituximab is associated with significant symptom relief in patients with chronic fatigue syndrome (CFS), Norwegian researchers report.

The timing of the improvement, between 2 and 7 months after treatment, suggests that "CFS is an autoimmune disease and may be consistent with the gradual elimination of autoantibodies preceding clinical responses," write Øystein Fluge (Haukeland University Hospital, Bergen) and colleagues.

The researchers previously observed that a patient with CFS experienced significant symptom improvement while they were undergoing chemotherapy with rituximab for unrelated Hodgkin's lymphoma. A pilot study in three further patients with CFS showed similar findings.

To investigate further, Fluge and team conducted a double-blind, placebo-controlled phase II study in which 30 CFS patients were randomly assigned to receive either two doses of rituximab 500 mg/m2 or saline, given two weeks apart, and then followed-up for 12 months.

Before treatment, the patients recorded their CFS disease symptoms in the previous 3 months on a 10-point visual analogue scale, where increasing score was associated with increasing disease severity.

During follow-up, they recorded overall change in symptoms, compared with baseline, every 2 weeks. Change was classed as major worsening, moderate worsening, slight worsening, no change, slight improvement, moderate improvement, or major improvement.

The researchers observed that significantly more patients in the rituximab group than in the placebo group reported a major or moderate overall improvement - defined as lasting improvements in self-reported fatigue score during follow-up - at 67% versus 13%.

The mean response duration for the 10 patients that were rituximab responders was 25 weeks, while four patients had clinical response durations beyond the 12-month study period.

All but one patient in the rituximab group showed B-cell depletion at 1 month post-treatment, but there were no significant differences in B-cell levels between rituximab responders and nonresponders.

The researchers found that there was a significant interaction between time and self- and physician-reported fatigue scores, with differences between the rituximab and placebo groups greatest between 6 and 10 months after the intervention.

Only one of the 10 responders in the rituximab group had an ''early'' response pattern, with the major response starting from 2 months, while the remaining nine responded later, starting to improve from between 3-7 months after treatment.

"We speculate that the responses occurring late after intervention could be explained by the elimination of disease-associated autoantibodies, while the early response pattern could be related to interaction of B-cells with T-cells in antigen presentation, as suggested in systemic lupus erythematosus," write Fluge et al in the journal PLoS ONE.

Of note, there were no serious adverse events or infections, and xenotropic murine leukemia virus-related virus - a suggested cause of CFS - was not detected in any of the patients.

The researchers say that it is unclear whether the five patients in the rituximab group who did not achieve a significant response during follow-up have a CFS pathogenesis that is unrelated to B-lymphocytes, or whether they could achieve a clinical response through prolonged B-cell depletion with Rituximab maintenance therapy.

They conclude that their findings "will impact future research efforts in CFS."

By Laura Dean

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