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Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: A preliminary case series
BMC Neurology, 07/02/09
Fluge O et al. – Observations suggest that B-lymphocytes are involved in chronic fatigue syndrome (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.
Methods- Basis for this case series was the observation that a patient with CFS had unexpected, marked recovery of CFS symptoms lasting for 5 months during and after cytotoxic chemotherapy for Hodgkin's disease
- Postulation was that the transient recovery could be related to MTX treatment, which induces immunomodulation in part through B-cell depletion
- In a case series this patient and 2 additional CFS pts were B-cell depleted by infusion of the monoclonal anti-CD20 antibody rituximab
- All 3 had improvement of all CFS symptoms
- Patients 1 and 2 had major amelioration from 6 wks after intervention, patient 3 slight improvement from the same time, but then improved markedly from 26 wks after intervention
- Symptomatic effect lasted until wks 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 3 had marked symptom improvement, mimicking their first response
- After new symptom recurrence, pts 1 and 2 were given weekly oral MTX, patient 1 having effect also from this agent
- Pts 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
Oystein Fluge and Olav Mella, 07/06/09
| This study of 3 pilot patients demonstrated that B-cell depletion resulted in marked, but transient, improvement of all CFS-related symptoms, indicating that at least a subset of CFS patients have their symptoms maintained through B-lymphocyte action, either directly or indirectly through other parts of the immune system. In addition to the impressive quality of life enhancement seen, thus pointing at a potential future drug treatment, the study turns focus toward the role of B-lymphocytes in this poorly understood entity and supports biological mechanisms as crucial for symptom development. As all perceptible, disease-related changes were ameliorated by the repeated drug interventions, a central mechanism seem to be touched by the manipulation and further biological studies may open way for understanding the underlying pathogenesis of CFS. Presently, a randomised, double-blinded study of 30 CFS patients is being performed to estimate the response rate to be expected from B-cell depletion in this, until now, merely symptom-based entity. |
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