Shorter infusion time of ocrelizumab: Results from the randomized, double-blind ENSEMBLE PLUS substudy in patients with relapsing-remitting multiple sclerosis

被引：19

作者：

Hartung, H-P ^{[1
,2
]}

Berger, T. ^{[3
]}

Bermel, R. A. ^{[4
]}

Brochet, B. ^{[5
]}

Carroll, W. M. ^{[6
]}

Holmoy, T. ^{[7
,8
]}

Karabudak, R. ^{[9
]}

Killestein, J. ^{[10
]}

Nos, C. ^{[11
]}

Patti, F. ^{[12
,13
]}

Ross, A. Perrin ^{[14
]}

Vanopdenbosch, L. ^{[15
]}

Vollmer, T. ^{[16
]}

Buffels, R. ^{[17
]}

Garas, M. ^{[17
]}

Kadner, K. ^{[17
]}

Manfrini, M. ^{[17
]}

Wang, Q. ^{[17
]}

Freedman, M. S. ^{[18
,19
]}

机构：

[1] Heinrich Heine Univ Dusseldorf, Ctr Neurol & Neuropsychiat, Dept Neurol, UKD, Dusseldorf, Germany

[2] Heinrich Heine Univ Dusseldorf, LVR Klinikurn, Dusseldorf, Germany

[3] Med Univ Vienna, Dept Neurol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria

[4] Cleveland Clin, Neurol Inst, Mellen Ctr MS, 9500 Euclid Ave, Cleveland, OH 44195 USA

[5] Univ Bordeaux, Neuroctr Magendie, INSERM U 1215, Bordeaux, France

[6] Univ Western Australia, Sir Charles Gairdner Hosp, Perron Inst Neurol & Translat Sci, Dept Neurol, Nedlands, WA 6009, Australia

[7] Akershus Univ Hosp, Dept Neurol, POB 1000, N-1478 Lorenskog, Norway

[8] Univ Oslo, Inst Clin Med, Oslo, Norway

[9] Hacettepe Univ, Dept Neurol, Fac Med, Ankara, Turkey

[10] Vrije Univ Amsterdam, MS Ctr Amsterdam, Dept Neurol, Amsterdam Neurosci,Amsterdam UMC, Amsterdam, Netherlands

[11] Vall dHebron Hosp Univ, Ctr Esclerosi Mutiple Catalunya Cemcat, Barcelona 08035, Spain

[12] Univ Catania, Dept Med & Surg Sci & Adv Technol, GF Ingrassia, Neurosci Sect, PO Policlin G Rodol,Via Santa Sofia 78, I-95123 Catania, Italy

[13] Univ Catania, Multiple Sclerosis Ctr, PO Policlin G Rodol,Via Santa Sofia 78, I-95123 Catania, Italy

[14] Loyola Univ Chicago, Maywood, IL 60660 USA

[15] AZ Sint Jan Brugge Oostende, Dept Neurol, Ruddershove 10, B-8000 Brugge, Belgium

[16] Univ Colorado, Anschutz Med Campus,12631 East 17th St, Aurora, CO 80045 USA

[17] F Hoffmann La Roche Ltd, Grenzacherstr 124, CH-4070 Basel, Switzerland

[18] Univ Ottawa, Ottawa, ON, Canada

[19] Ottawa Hosp, Res Inst, Ottawa, ON, Canada

来源：

MULTIPLE SCLEROSIS AND RELATED DISORDERS | 2020年 / 46卷

关键词：

Ocrelizumab; shorter infusion; relapsing-remitting multiple sclerosis; infusion-related reaction;

D O I：

10.1016/j.msard.2020.102492

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background: Ocrelizumab is an approved intravenously administered anti-CD20 antibody for multiple sclerosis (MS). Shortening the 600 mg infusion to 2 hours reduces the total site stay from 5.5-6 hours (approved infusion duration including mandatory pre-medication and post-infusion observation) to 4 hours. The safety profile of shorter-duration ocrelizumab infusions was investigated using results from ENSEMBLE PLUS. Methods: ENSEMBLE PLUS is a randomized, double-blind substudy to the single-arm ENSEMBLE study (NCT03085810). In ENSEMBLE, patients with early-stage relapsing-remitting MS received ocrelizumab 600 mg infusions every 24 weeks for 192 weeks. In ENSEMBLE PLUS, ocrelizumab 600 mg administered over the approved 3.5-hour infusion time (conventional duration) is compared with a 2-hour infusion (shorter duration); the durations of the initial infusions (2x300 mg, 14 days apart) were unaffected. The primary endpoint was the proportion of patients with infusion-related reactions (IRRs) following the first Randomized Dose. Results: From November 1, 2018, to December 13, 2019, 745 patients were randomized 1:1 to the conventional or shorter infusion group. At the first Randomized Dose, 99/373 patients (26.5%) in the conventional and 107/372 patients (28.8%) in the shorter infusion group experienced IRRs. The majority of IRRs were mild or moderate; >99% of all IRRs resolved without sequelae in both groups (conventional infusion group, 99/99; shorter infusion group, 106/107). No IRRs were serious, life-threatening, or fatal. No IRR-related discontinuations occurred. During the first Randomized Dose, 22/373 (5.9%) and 39/372 (10.5%) patients in the conventional and shorter infusion groups, respectively, had IRRs leading to infusion slowing/interruption. Adverse events were consistent with the known safety profile of ocrelizumab. Conclusion: The rates and severity of IRRs were similar between conventional and shorter infusions. No new safety signals were detected. Shortening the infusion time to 2 hours reduces the total site stay time (including

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