RT Journal Article
SR Electronic
T1 Rapid depletion of B lymphocytes by ultra-low-dose rituximab delivered intrathecally
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e79
DO 10.1212/NXI.0000000000000079
VO 2
IS 2
A1 Svenningsson, Anders
A1 Bergman, Joakim
A1 Dring, Ann
A1 Vågberg, Mattias
A1 Birgander, Richard
A1 Lindqvist, Thomas
A1 Gilthorpe, Jonathan
A1 Bergenheim, Tommy
YR 2015
UL http://nn.neurology.org/content/2/2/e79.abstract
AB Objective: We are conducting an open-label phase 1b study on the efficacy of intrathecal (IT) administration of rituximab, provided via an Ommaya reservoir, for the treatment of progressive multiple sclerosis (PMS). The objective of this initial study was to monitor B lymphocytes in peripheral blood (PB) and CSF from the first 10 patients 1 year posttreatment.Methods: Dose titration was performed with daily escalation from 1 mg to 25 mg IT rituximab (n = 3). Lymphocyte subpopulations were monitored daily during dose escalation in PB by flow cytometry and subsequently every 3 months for 1 year, after a total dose of 3 × 25 mg. PB B-lymphocyte subpopulations for the remaining patients (n = 7) were monitored at regular intervals. CSF lymphocyte subpopulations for all patients were monitored by flow cytometry every 2–3 months.Results: The PB B-lymphocyte count dropped rapidly after the first 2 injections (total dose of 3.5 mg IT rituximab) to undetectable levels. Three 25-mg doses given once per week depleted peripheral B lymphocytes entirely for the following 3–6 month period.Conclusions: Monoclonal antibodies seem to rapidly redistribute to the peripheral compartment following IT injection. Ultra-low doses of rituximab given IT are sufficient to cause complete depletion of peripheral B lymphocytes, indicating that low-dose IT treatment has the potential to be effective in both the CNS and systemic compartments.Classification of evidence: This study provides Class IV evidence that for patients with PMS, rituximab provided via an Ommaya reservoir depletes peripheral blood B lymphocytes.BBB=blood-brain barrier; EAE=experimental autoimmune encephalomyelitis; IT=intrathecal; MS=multiple sclerosis; PB=peripheral blood; PMS=progressive MS