Sarilumab, a fully human monoclonal antibody against IL-6Rα in patients with rheumatoid arthritis and an inadequate response to methotrexate : efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions..
OBJECTIVES: To evaluate safety and efficacy of weekly (qw) and every other week (q2w) dosing of sarilumab, a fully human anti-interleukin 6 receptor α (anti-IL-6Rα) monoclonal antibody, for moderate-to-severe rheumatoid arthritis (RA).
METHODS: In this dose-ranging study, patients (n=306) with active RA, despite methotrexate, were randomly assigned to placebo or one of five subcutaneous doses/regimens of sarilumab: 100 mg q2w, 150 mg q2w, 100 mg qw, 200 mg q2w, 150 mg qw for 12 weeks, plus methotrexate. The primary end point was ACR20 at Week 12. Secondary endpoints included ACR50, ACR70, Disease Activity Score in 28 joints (C reactive protein). Safety, pharmacokinetics, pharmacodynamics and efficacy in population subgroups were assessed.
RESULTS: The proportion of patients achieving an ACR20 response compared with placebo was significantly higher for sarilumab 150 mg qw (72.0% vs 46.2%, multiplicity adjusted p=0.0203). Higher ACR20 responses were also attained with 150 mg q2w (67%; unadjusted (nominal) p=0.0363) and 200 mg q2w (65%; unadjusted p=0.0426) versus placebo. Sarilumab ≥150 mg q2w reduced C reactive protein, which did not return to baseline between dosing intervals. Infections were the most common adverse event; none were serious. Changes in laboratory values (neutropenia, transaminases and lipids) were consistent with reports with other IL-6Rα inhibitors.
CONCLUSIONS: Sarilumab improved signs and symptoms of RA over 12 weeks in patients with moderate-to-severe RA with a safety profile similar to reports with other IL-6 inhibitors. Sarilumab 150 mg and sarilumab 200 mg q2w had the most favourable efficacy, safety and dosing convenience and are being further evaluated in Phase III.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:73 |
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| Enthalten in: |
Annals of the rheumatic diseases - 73(2014), 9 vom: 02. Sept., Seite 1626-34 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huizinga, Tom W J [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.10.2014 Date Revised 09.04.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1136/annrheumdis-2013-204405 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM233273131 |
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| 041 | |a eng | ||
| 100 | 1 | |a Huizinga, Tom W J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Sarilumab, a fully human monoclonal antibody against IL-6Rα in patients with rheumatoid arthritis and an inadequate response to methotrexate |b efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial |
| 264 | 1 | |c 2014 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 16.10.2014 | ||
| 500 | |a Date Revised 09.04.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. | ||
| 520 | |a OBJECTIVES: To evaluate safety and efficacy of weekly (qw) and every other week (q2w) dosing of sarilumab, a fully human anti-interleukin 6 receptor α (anti-IL-6Rα) monoclonal antibody, for moderate-to-severe rheumatoid arthritis (RA) | ||
| 520 | |a METHODS: In this dose-ranging study, patients (n=306) with active RA, despite methotrexate, were randomly assigned to placebo or one of five subcutaneous doses/regimens of sarilumab: 100 mg q2w, 150 mg q2w, 100 mg qw, 200 mg q2w, 150 mg qw for 12 weeks, plus methotrexate. The primary end point was ACR20 at Week 12. Secondary endpoints included ACR50, ACR70, Disease Activity Score in 28 joints (C reactive protein). Safety, pharmacokinetics, pharmacodynamics and efficacy in population subgroups were assessed | ||
| 520 | |a RESULTS: The proportion of patients achieving an ACR20 response compared with placebo was significantly higher for sarilumab 150 mg qw (72.0% vs 46.2%, multiplicity adjusted p=0.0203). Higher ACR20 responses were also attained with 150 mg q2w (67%; unadjusted (nominal) p=0.0363) and 200 mg q2w (65%; unadjusted p=0.0426) versus placebo. Sarilumab ≥150 mg q2w reduced C reactive protein, which did not return to baseline between dosing intervals. Infections were the most common adverse event; none were serious. Changes in laboratory values (neutropenia, transaminases and lipids) were consistent with reports with other IL-6Rα inhibitors | ||
| 520 | |a CONCLUSIONS: Sarilumab improved signs and symptoms of RA over 12 weeks in patients with moderate-to-severe RA with a safety profile similar to reports with other IL-6 inhibitors. Sarilumab 150 mg and sarilumab 200 mg q2w had the most favourable efficacy, safety and dosing convenience and are being further evaluated in Phase III | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Cytokines | |
| 650 | 4 | |a DMARDs (biologic) | |
| 650 | 4 | |a Rheumatoid Arthritis | |
| 650 | 4 | |a Treatment | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a Antirheumatic Agents |2 NLM | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a Receptors, Interleukin-6 |2 NLM | |
| 650 | 7 | |a C-Reactive Protein |2 NLM | |
| 650 | 7 | |a 9007-41-4 |2 NLM | |
| 650 | 7 | |a sarilumab |2 NLM | |
| 650 | 7 | |a NU90V55F8I |2 NLM | |
| 650 | 7 | |a Methotrexate |2 NLM | |
| 650 | 7 | |a YL5FZ2Y5U1 |2 NLM | |
| 700 | 1 | |a Fleischmann, Roy M |e verfasserin |4 aut | |
| 700 | 1 | |a Jasson, Martine |e verfasserin |4 aut | |
| 700 | 1 | |a Radin, Allen R |e verfasserin |4 aut | |
| 700 | 1 | |a van Adelsberg, Janet |e verfasserin |4 aut | |
| 700 | 1 | |a Fiore, Stefano |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Xiaohong |e verfasserin |4 aut | |
| 700 | 1 | |a Yancopoulos, George D |e verfasserin |4 aut | |
| 700 | 1 | |a Stahl, Neil |e verfasserin |4 aut | |
| 700 | 1 | |a Genovese, Mark C |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:73 |g year:2014 |g number:9 |g day:02 |g month:09 |g pages:1626-34 |
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