Rituximab Serum Concentrations and Anti-Rituximab Antibodies During B-Cell Depletion Therapy for Myalgic Encephalopathy/Chronic Fatigue Syndrome |
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| Institution: | 1. Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway;2. Sanquin Diagnostic Services, Amsterdam, The Netherlands;3. Section of Clinical Pharmacology, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway;4. Department of Clinical Science, University of Bergen, Norway;1. Cure SMA, Chicago, IL, USA;2. Silicon Valley Research Group, Inc, San Jose, CA, USA;1. Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan;2. Department of Radiobiology and Medical Engineering, Hokkaido University Graduate School of Medicine, Sapporo, Japan;3. Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan;1. Institute of Pharmacology, Università Cattolica Del S. Cuore, Rome, Italy;2. Pharmacology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy;3. Manchester Institute of Innovation Research, The University of Manchester, Manchester, United Kingdom;1. Department of Neurology, Johns Hopkins University, Baltimore, MD, USA;2. Department of Neurology, University of California San Francisco, San Francisco, CA, USA;3. Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA;4. Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA |
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| Abstract: | PurposePrevious Phase II trials indicated clinical benefit from B-cell depletion using the monoclonal anti-CD20 antibody rituximab in patients with myalgic encephalopathy/chronic fatigue syndrome (ME/CFS). The association between rituximab serum concentrations and the effect and clinical relevance of antidrug antibodies (ADAs) against rituximab in ME/CFS is unknown. We retrospectively measured rituximab concentrations and ADAs in serum samples from patients included in an open-label Phase II trial with maintenance rituximab treatment (KTS-2-2010) to investigate possible associations with clinical improvement and clinical and biochemical data.MethodsPatients with ME/CFS fulfilling the Canadian criteria received rituximab (500 mg/m2) infusions: 2 infusions 2 weeks apart (induction), followed by maintenance treatment at 3, 6, 10, and 15 months. The measured rituximab concentrations and ADAs in serum samples included 23 of 28 patients from the trial.FindingsThere were no significant differences in mean serum rituximab concentrations between 14 patients experiencing clinical improvement versus 9 patients with no improvement. Female patients had higher mean serum rituximab concentrations than male patients at 3 months (P = 0.05). There was a significant negative correlation between B-cell numbers in peripheral blood at baseline and rituximab serum concentration at 3 months (r = ?0.47; P = 0.03). None of the patients had ADAs at any time point.ImplicationsClinical improvement of patients with ME/CFS in the KTS-2-2010 trial was not related to rituximab serum concentrations or ADAs. This finding is also in line with a recent randomized trial questioning the efficacy of rituximab in ME/CFS. Rituximab concentrations and ADAs still offer supplemental information when interpreting the results of these trials. |
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| Keywords: | antidrug antibodies B-cell depletion chronic fatigue syndrome myalgic encephalopathy rituximab rituximab concentrations |
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