1. B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
- Author
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Solvang Ah, Merethe Eide Gotaas, Kine Alme, Ingrid Herder, Katarina Lien, Kristin Risa, Lonar Ae, Kari Sørland, Kvammen Ø, Martinsen Ss, Bohnen Lmlj, Gya Aes, Christoph Schäfer, Hanne Thürmer, Olav Mella, Irini Ktoridou-Valen, Ove Bruland, Jörg Aßmus, Katarzyna A. Baranowska, Olav Dahl, Ingrid Gurvin Rekeland, Petter C. Borchgrevink, and Øystein Fluge
- Subjects
Adult ,Male ,medicine.medical_specialty ,Placebo-controlled study ,Placebo ,Severity of Illness Index ,01 natural sciences ,Lymphocyte Depletion ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Double-Blind Method ,Multicenter trial ,Internal medicine ,Severity of illness ,Internal Medicine ,Chronic fatigue syndrome ,medicine ,Humans ,030212 general & internal medicine ,0101 mathematics ,Infusions, Intravenous ,B-Lymphocytes ,Fatigue Syndrome, Chronic ,business.industry ,Surrogate endpoint ,010102 general mathematics ,Repeated measures design ,General Medicine ,medicine.disease ,Female ,Rituximab ,business ,medicine.drug - 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.
- Published
- 2019
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