Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis : APLIOS, a randomized phase-2 study
Bar-Or, Amit (University of Pennsylvania)
Wiendl, Heinz (University of Münster)
Montalban, Xavier (Hospital Universitari Vall d'Hebron)
Alvarez, Enrique (University of Colorado)
Davydovskaya, Maria (Pirogov Russian National Research Medical University)
Delgado, Silvia (University of Miami)
Evdoshenko, Evgeniy P. (St Petersburg Center for Multiple Sclerosis and Other Autoimmune Diseases)
Giedraitiene, Natasa (Vilnius University)
Gross-Paju, Katrin (Institute of Health Care Technology)
Haldre, Sulev (University of Tartu)
Herrman, Craig E. (JWM Neurology)
Izquierdo, Guillermo (Hospital Vithas Sevilla)
Karelis, Guntis (Riga East University Hospital)
Leutmezer, Fritz (Medical University of Vienna)
Mares, Miroslav (Pardubice Regional Hospital)
Meca-Lallana, Jose Eustasio (Hospital Universitario Virgen de la Arrixaca (Múrcia))
Mickeviciene, Dalia (Lithuanian University of Health Sciences)
Nicholas, Jacqueline (Riverside Methodist Hospital)
Robertson, Derrick S. (University of South Florida)
Sazonov, Denis V. (Department of Clinical Trials FSBIH SDMC of FMBA of Russia)
Sharlin, Kenneth (Sharlin Health and Neurology)
Sundaram, Bharathy (Texas Institute for Neurological Disorders)
Totolyan, Natalia (Pavlov First State Medical University of St. Petersburg)
Vachova, Marta (Teplice Hospital)
Valis, Martin (Charles University)
Bagger, Morten (Novartis)
Häring, Dieter A. (Novartis)
Ludwig, Inga (Novartis)
Willi, Roman (Novartis)
Zalesak, Martin (Novartis)
Su, Wendy (Novartis)
Merschhemke, Martin (Novartis)
Fox, Edward J. (Central Texas Neurology Consultants PA)
Universitat Autònoma de Barcelona

Fecha:	2022
Descripción:	15 pàg.
Resumen:	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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Autoinjector pen ; Bioequivalence ; Multiple sclerosis ; Ofatumumab ; Pharmacokinetics ; Pre-filled syringe
Publicado en:	Multiple sclerosis, Vol. 28 Núm. 6 (2022) , p. 910-924, ISSN 1477-0970

DOI: 10.1177/13524585211044479
PMID: 34605319

15 p, 877.1 KB

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