Sistema de Salut de Catalunya
Institut Català de la Salut
[Bar-Or A] Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. [Wiendl H] Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany. [Montalban X] Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Alvarez E] Department of Neurology, Rocky Mountain MS Center, University of Colorado, Aurora, CO, USA. [Davydovskaya M] Pirogov Russian National Research Medical University, Moscow, Russian Federation. [Delgado SR] MS Center and Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA
Vall d'Hebron Barcelona Hospital Campus
2022-07-19T10:25:42Z
2022-07-19T10:25:42Z
2021
2022-05
Ofatumumab; Multiple sclerosis; Pharmacokinetics
Ofatumumab; Esclerosis múltiple; Farmacocinética
Ofatumumab; Esclerosi múltiple; Farmacocinètica
Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8–12. B-cell depletion and safety/tolerability were assessed. Results: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. Conclusion: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion.
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: the APLIOS trial was funded by Novartis Pharmaceuticals. Novartis Pharmaceuticals supported the development of this manuscript, provided data analyses according to the direction of the authors, and paid for medical writing support.
Article
Published version
English
Esclerosi múltiple; Anticossos monoclonals; Injeccions hipodèrmiques; DISEASES::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis; Other subheadings::Other subheadings::Other subheadings::/chemically induced; ENFERMEDADES::enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple; Otros calificadores::Otros calificadores::Otros calificadores::/inducido químicamente
SAGE Publications
Multiple sclerosis;28(6)
https://doi.org/10.1177/13524585211044479
Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
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