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

@entity1 @entity137 @entity2225 @entity1398 @entity1892 @entity56 @entity5815 @entity2408 @entity792
BACKGROUND: Myalgic @entity5815 (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- @entity2225 antibody rituximab can yield clinical benefit in ME/CFS. METHODS: In this single-center, open-label, one-armed phase II study (NCT01156909), 29 @entity1 were included for treatment with @entity2408 (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 @entity1 (intention to treat). Clinically significant responses were seen in 18 out of 28 @entity1 (64%) receiving rituximab maintenance treatment. For these 18 @entity1 , 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 @entity1 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 @entity1 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 @entity1 had an @entity56 to rituximab and two had an episode of uncomplicated late-onset @entity1398 . Eight @entity1 experienced one or more transient symptom flares after rituximab infusions. There was no unexpected @entity137 . CONCLUSION: In a subgroup of ME/CFS @entity1 , 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 @entity1 than in @entity1 , and a previously demonstrated increase in @entity1892 risk for elderly ME/CFS @entity1 , suggest that ME/CFS may be a variant of an @entity792 . TRIAL REGISTRATION: ClinicalTrials.gov NCT01156909.
