Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series

Abstract

Background: Chronic fatigue syndrome (CFS) is a disease of unknown aetiology. A patient with CFS had unexpected, marked recovery of CFS symptoms lasting for five months during and after cytotoxic chemotherapy for Hodgkin's disease. We reasoned that the transient CFS recovery was related to methotrexate treatment, which induces immunomodulation in part through B-cell depletion.

Methods: In a case series, this patient and two additional CFS patients were B-cell depleted by infusion of the monoclonal anti-CD20 antibody rituximab.

Results: All three had improvement of all CFS symptoms. Patients 1 and 2 had major amelioration from 6 weeks after intervention, patient 3 slight improvement from the same time, but then improved markedly from 26 weeks after intervention. The symptomatic effect lasted until weeks 16, 18 and 44, respectively. At relapse, all were retreated with a single (patient 1) or double rituximab infusion (patients 2 and 3). Again, all three had marked symptom improvement, mimicking their first response. After new symptom recurrence, patients 1 and 2 were given weekly oral methotrexate, patient 1 having effect also from this agent. Patients 1 and 2 were again treated for a third rituximab infusion after new relapse, again with a marked clinical benefit. No unexpected toxicity was seen.

Conclusion: These observations suggest that B-lymphocytes are involved in CFS pathogenesis for a subset of patients. Benefit for all CFS symptoms, the delayed symptom relief following B-cell depletion, the kinetics of relapses, and the effect also from methotrexate treatment, provide suggestive evidence that B-cells play a significant role in the ongoing clinical features, and that CFS may be amenable to therapeutic interventions aimed at modifying B-cell number and function. More systematic investigations of this therapeutic strategy, and of its biological basis, are now needed.

Figure 1

CFS symptoms during follow-up of three patients after first rituximab infusion. The patients had regular consultations with 1–2 month intervals, and telephone contact with 1–2 week intervals for the follow-up period. The patients kept record of their symptom development and assessed this figure, to assure that the joint interpretation of the two investigators was in accordance with their opinion. In each patient all CFS symptoms in general changed synchronously, thus the overall symptom status was subjectively scored from 1 (no symptoms) to 10 (severe symptoms) on the vertical scale. Below the figure B-cell numbers in peripheral blood are shown, for each patient, and plotted at the appropriate time during follow-up (i.e. weeks from first rituximab infusion). R: rituximab infusion. M: start of oral weekly methotrexate.