Rituximab Serum Concentrations and Anti-Rituximab Antibodies During B-Cell Depletion Therapy for Myalgic Encephalopathy/Chronic Fatigue Syndrome.

Abstract

PURPOSE: Previous 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. METHODS: Patients with ME/CFS fulfilling the  Canadian criteria received rituximab (500 mg/m(2)) 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. FINDINGS: There 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. IMPLICATIONS: Clinical  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.