B-Lymphocyte Depletion in Myalgic Encephalopathy/ Chronic Fatigue Syndrome. An Open-Label Phase II Study with Rituximab Maintenance Treatment.

Abstract

BACKGROUND: Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a disease of unknown etiology. We previously reported a pilot case series followed by a  small, randomized, placebo-controlled phase II study, suggesting that B-cell  depletion using the monoclonal anti-CD20 antibody rituximab can yield clinical  benefit in ME/CFS. METHODS: In this single-center, open-label, one-armed phase II  study (NCT01156909), 29 patients were included for treatment with rituximab (500  mg/m2) two infusions two weeks apart, followed by maintenance rituximab infusions  after 3, 6, 10 and 15 months, and with follow-up for 36 months. FINDINGS: Major  or moderate responses, predefined as lasting improvements in self-reported  Fatigue score, were detected in 18 out of 29 patients (intention to treat).  Clinically significant responses were seen in 18 out of 28 patients (64%)  receiving rituximab maintenance treatment. For these 18 patients, the mean  response durations within the 156 weeks study period were 105 weeks in 14 major  responders, and 69 weeks in four moderate responders. At end of follow-up (36  months), 11 out of 18 responding patients were still in ongoing clinical  remission. For major responders, the mean lag time from first rituximab infusion  until start of clinical response was 23 weeks (range 8-66). Among the nine  patients from the placebo group in the previous randomized study with no  significant improvement during 12 months follow-up after saline infusions, six  achieved a clinical response before 12 months after rituximab maintenance  infusions in the present study. Two patients had an allergic reaction to  rituximab and two had an episode of uncomplicated late-onset neutropenia. Eight  patients experienced one or more transient symptom flares after rituximab  infusions. There was no unexpected toxicity. CONCLUSION: In a subgroup of ME/CFS  patients, prolonged B-cell depletion with rituximab maintenance infusions was  associated with sustained clinical responses. The observed patterns of delayed  responses and relapse after B-cell depletion and regeneration, a three times  higher disease prevalence in women than in men, and a previously demonstrated  increase in B-cell lymphoma risk for elderly ME/CFS patients, suggest that ME/CFS  may be a variant of an autoimmune disease. TRIAL REGISTRATION: ClinicalTrials.gov  NCT01156909.