B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.

Abstract

BACKGROUND: Previous phase 2 trials indicated benefit from B-lymphocyte depletion in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). OBJECTIVE: To  evaluate the effect of the monoclonal anti-CD20 antibody rituximab versus placebo  in patients with ME/CFS. DESIGN: Randomized, placebo-controlled, double-blind,  multicenter trial. (ClinicalTrials.gov: NCT02229942). SETTING: 4 university  hospitals and 1 general hospital in Norway. PATIENTS: 151 patients aged 18 to 65  years who had ME/CFS according to Canadian consensus criteria and had had the  disease for 2 to 15 years. INTERVENTION: Treatment induction with 2 infusions of  rituximab, 500 mg/m2 of body surface area, 2 weeks apart, followed by 4  maintenance infusions with a fixed dose of 500 mg at 3, 6, 9, and 12 months (n =  77), or placebo (n = 74). MEASUREMENTS: Primary outcomes were overall response  rate (fatigue score ≥4.5 for ≥8 consecutive weeks) and repeated measurements of  fatigue score over 24 months. Secondary outcomes included repeated measurements  of self-reported function over 24 months, components of the Short Form-36 Health  Survey and Fatigue Severity Scale over 24 months, and changes from baseline to 18  months in these measures and physical activity level. Between-group differences  in outcome measures over time were assessed by general linear models for repeated  measures. RESULTS: Overall response rates were 35.1% in the placebo group and  26.0% in the rituximab group (difference, 9.2 percentage points [95% CI, -5.5 to  23.3 percentage points]; P = 0.22). The treatment groups did not differ in  fatigue score over 24 months (difference in average score, 0.02 [CI, -0.27 to  0.31]; P = 0.80) or any of the secondary end points. Twenty patients (26.0%) in  the rituximab group and 14 (18.9%) in the placebo group had serious adverse  events. LIMITATION: Self-reported primary outcome measures and possible recall  bias. CONCLUSION: B-cell depletion using several infusions of rituximab over 12  months was not associated with clinical improvement in patients with ME/CFS.  PRIMARY FUNDING SOURCE: The Norwegian Research Council, Norwegian Regional Health  Trusts, Kavli Trust, MEandYou Foundation, and Norwegian ME Association.