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Ofatumumab versus Teriflunomide in Multiple Sclerosis

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ASCLEPIOS I and ASCLEPIOS II Trial Groups ; Sørensen, Per Soelberg. / Ofatumumab versus Teriflunomide in Multiple Sclerosis. I: The New England journal of medicine. 2020 ; Bind 383, Nr. 6. s. 546-557.

Bibtex

@article{2cb46a15dc5749b989a82f976d772205,
title = "Ofatumumab versus Teriflunomide in Multiple Sclerosis",
abstract = "BACKGROUND: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known.METHODS: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume.RESULTS: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P<0.001) and 0.10 and 0.25 in trial 2 (difference, -0.15; 95% CI, -0.20 to -0.09; P<0.001). In the pooled trials, the percentage of patients with disability worsening confirmed at 3 months was 10.9% with ofatumumab and 15.0% with teriflunomide (hazard ratio, 0.66; P = 0.002); the percentage with disability worsening confirmed at 6 months was 8.1% and 12.0%, respectively (hazard ratio, 0.68; P = 0.01); and the percentage with disability improvement confirmed at 6 months was 11.0% and 8.1% (hazard ratio, 1.35; P = 0.09). The number of gadolinium-enhancing lesions per T1-weighted MRI scan, the annualized rate of lesions on T2-weighted MRI, and serum neurofilament light chain levels, but not the change in brain volume, were in the same direction as the primary end point. Injection-related reactions occurred in 20.2% in the ofatumumab group and in 15.0% in the teriflunomide group (placebo injections). Serious infections occurred in 2.5% and 1.8% of the patients in the respective groups.CONCLUSIONS: Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide. (Funded by Novartis; ASCLEPIOS I and II ClinicalTrials.gov numbers, NCT02792218 and NCT02792231.).",
keywords = "Adult, Antibodies, Monoclonal, Humanized/adverse effects, B-Lymphocytes, Brain/pathology, Crotonates/adverse effects, Disease Progression, Double-Blind Method, Female, Humans, Injections, Subcutaneous/adverse effects, Kaplan-Meier Estimate, Magnetic Resonance Imaging, Male, Multiple Sclerosis, Relapsing-Remitting/drug therapy, T-Lymphocytes, Toluidines/adverse effects",
author = "Hauser, {Stephen L} and Amit Bar-Or and Cohen, {Jeffrey A} and Giancarlo Comi and Jorge Correale and Coyle, {Patricia K} and Cross, {Anne H} and {de Seze}, Jerome and David Leppert and Xavier Montalban and Krzysztof Selmaj and Heinz Wiendl and Cecile Kerloeguen and Roman Willi and Bingbing Li and Algirdas Kakarieka and Davorka Tomic and Alexandra Goodyear and Ratnakar Pingili and H{\"a}ring, {Dieter A} and Krishnan Ramanathan and Martin Merschhemke and Ludwig Kappos and {ASCLEPIOS I and ASCLEPIOS II Trial Groups} and S{\o}rensen, {Per Soelberg}",
note = "Copyright {\textcopyright} 2020 Massachusetts Medical Society.",
year = "2020",
month = aug,
day = "6",
doi = "10.1056/NEJMoa1917246",
language = "English",
volume = "383",
pages = "546--557",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachusetts Medical Society",
number = "6",

}

RIS

TY - JOUR

T1 - Ofatumumab versus Teriflunomide in Multiple Sclerosis

AU - Hauser, Stephen L

AU - Bar-Or, Amit

AU - Cohen, Jeffrey A

AU - Comi, Giancarlo

AU - Correale, Jorge

AU - Coyle, Patricia K

AU - Cross, Anne H

AU - de Seze, Jerome

AU - Leppert, David

AU - Montalban, Xavier

AU - Selmaj, Krzysztof

AU - Wiendl, Heinz

AU - Kerloeguen, Cecile

AU - Willi, Roman

AU - Li, Bingbing

AU - Kakarieka, Algirdas

AU - Tomic, Davorka

AU - Goodyear, Alexandra

AU - Pingili, Ratnakar

AU - Häring, Dieter A

AU - Ramanathan, Krishnan

AU - Merschhemke, Martin

AU - Kappos, Ludwig

AU - ASCLEPIOS I and ASCLEPIOS II Trial Groups

A2 - Sørensen, Per Soelberg

N1 - Copyright © 2020 Massachusetts Medical Society.

PY - 2020/8/6

Y1 - 2020/8/6

N2 - BACKGROUND: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known.METHODS: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume.RESULTS: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P<0.001) and 0.10 and 0.25 in trial 2 (difference, -0.15; 95% CI, -0.20 to -0.09; P<0.001). In the pooled trials, the percentage of patients with disability worsening confirmed at 3 months was 10.9% with ofatumumab and 15.0% with teriflunomide (hazard ratio, 0.66; P = 0.002); the percentage with disability worsening confirmed at 6 months was 8.1% and 12.0%, respectively (hazard ratio, 0.68; P = 0.01); and the percentage with disability improvement confirmed at 6 months was 11.0% and 8.1% (hazard ratio, 1.35; P = 0.09). The number of gadolinium-enhancing lesions per T1-weighted MRI scan, the annualized rate of lesions on T2-weighted MRI, and serum neurofilament light chain levels, but not the change in brain volume, were in the same direction as the primary end point. Injection-related reactions occurred in 20.2% in the ofatumumab group and in 15.0% in the teriflunomide group (placebo injections). Serious infections occurred in 2.5% and 1.8% of the patients in the respective groups.CONCLUSIONS: Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide. (Funded by Novartis; ASCLEPIOS I and II ClinicalTrials.gov numbers, NCT02792218 and NCT02792231.).

AB - BACKGROUND: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known.METHODS: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume.RESULTS: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P<0.001) and 0.10 and 0.25 in trial 2 (difference, -0.15; 95% CI, -0.20 to -0.09; P<0.001). In the pooled trials, the percentage of patients with disability worsening confirmed at 3 months was 10.9% with ofatumumab and 15.0% with teriflunomide (hazard ratio, 0.66; P = 0.002); the percentage with disability worsening confirmed at 6 months was 8.1% and 12.0%, respectively (hazard ratio, 0.68; P = 0.01); and the percentage with disability improvement confirmed at 6 months was 11.0% and 8.1% (hazard ratio, 1.35; P = 0.09). The number of gadolinium-enhancing lesions per T1-weighted MRI scan, the annualized rate of lesions on T2-weighted MRI, and serum neurofilament light chain levels, but not the change in brain volume, were in the same direction as the primary end point. Injection-related reactions occurred in 20.2% in the ofatumumab group and in 15.0% in the teriflunomide group (placebo injections). Serious infections occurred in 2.5% and 1.8% of the patients in the respective groups.CONCLUSIONS: Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide. (Funded by Novartis; ASCLEPIOS I and II ClinicalTrials.gov numbers, NCT02792218 and NCT02792231.).

KW - Adult

KW - Antibodies, Monoclonal, Humanized/adverse effects

KW - B-Lymphocytes

KW - Brain/pathology

KW - Crotonates/adverse effects

KW - Disease Progression

KW - Double-Blind Method

KW - Female

KW - Humans

KW - Injections, Subcutaneous/adverse effects

KW - Kaplan-Meier Estimate

KW - Magnetic Resonance Imaging

KW - Male

KW - Multiple Sclerosis, Relapsing-Remitting/drug therapy

KW - T-Lymphocytes

KW - Toluidines/adverse effects

U2 - 10.1056/NEJMoa1917246

DO - 10.1056/NEJMoa1917246

M3 - Journal article

C2 - 32757523

VL - 383

SP - 546

EP - 557

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 6

ER -

ID: 61640471