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MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial
OBJECTIVES: To determine the safety, tolerability and signs of efficacy of MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA). METHODS: Patients with active, moderate RA were enrolled in a randomised, multicent...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BMJ Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431325/ https://www.ncbi.nlm.nih.gov/pubmed/24534756 http://dx.doi.org/10.1136/annrheumdis-2013-204816 |
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author | Behrens, Frank Tak, Paul P Østergaard, Mikkel Stoilov, Rumen Wiland, Piotr Huizinga, Thomas W Berenfus, Vadym Y Vladeva, Stoyanka Rech, Juergen Rubbert-Roth, Andrea Korkosz, Mariusz Rekalov, Dmitriy Zupanets, Igor A Ejbjerg, Bo J Geiseler, Jens Fresenius, Julia Korolkiewicz, Roman P Schottelius, Arndt J Burkhardt, Harald |
author_facet | Behrens, Frank Tak, Paul P Østergaard, Mikkel Stoilov, Rumen Wiland, Piotr Huizinga, Thomas W Berenfus, Vadym Y Vladeva, Stoyanka Rech, Juergen Rubbert-Roth, Andrea Korkosz, Mariusz Rekalov, Dmitriy Zupanets, Igor A Ejbjerg, Bo J Geiseler, Jens Fresenius, Julia Korolkiewicz, Roman P Schottelius, Arndt J Burkhardt, Harald |
author_sort | Behrens, Frank |
collection | PubMed |
description | OBJECTIVES: To determine the safety, tolerability and signs of efficacy of MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA). METHODS: Patients with active, moderate RA were enrolled in a randomised, multicentre, double-blind, placebo-controlled, dose-escalation trial of intravenous MOR103 (0.3, 1.0 or 1.5 mg/kg) once a week for 4 weeks, with follow-up to 16 weeks. The primary outcome was safety. RESULTS: Of the 96 randomised and treated subjects, 85 completed the trial (n=27, 24, 22 and 23 for pooled placebo and MOR103 0.3, 1.0 and 1.5 mg/kg, respectively). Treatment emergent adverse events (AEs) in the MOR103 groups were mild or moderate in intensity and generally reported at frequencies similar to those in the placebo group. The most common AE was nasopharyngitis. In two cases, AEs were classified as serious because of hospitalisation: paronychia in a placebo subject and pleurisy in a MOR103 0.3 mg/kg subject. Both patients recovered fully. In exploratory efficacy analyses, subjects in the MOR103 1.0 and 1.5 mg/kg groups showed significant improvements in Disease Activity Score-28 scores and joint counts and significantly higher European League Against Rheumatism response rates than subjects receiving placebo. MOR103 1.0 mg/kg was associated with the largest reductions in disease activity parameters. CONCLUSIONS: MOR103 was well tolerated and showed preliminary evidence of efficacy in patients with active RA. The data support further investigation of this monoclonal antibody to GM-CSF in RA patients and potentially in those with other immune-mediated inflammatory diseases. TRIAL REGISTRATION NUMBER: NCT01023256 |
format | Online Article Text |
id | pubmed-4431325 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-44313252015-05-15 MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial Behrens, Frank Tak, Paul P Østergaard, Mikkel Stoilov, Rumen Wiland, Piotr Huizinga, Thomas W Berenfus, Vadym Y Vladeva, Stoyanka Rech, Juergen Rubbert-Roth, Andrea Korkosz, Mariusz Rekalov, Dmitriy Zupanets, Igor A Ejbjerg, Bo J Geiseler, Jens Fresenius, Julia Korolkiewicz, Roman P Schottelius, Arndt J Burkhardt, Harald Ann Rheum Dis Clinical and Epidemiological Research OBJECTIVES: To determine the safety, tolerability and signs of efficacy of MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA). METHODS: Patients with active, moderate RA were enrolled in a randomised, multicentre, double-blind, placebo-controlled, dose-escalation trial of intravenous MOR103 (0.3, 1.0 or 1.5 mg/kg) once a week for 4 weeks, with follow-up to 16 weeks. The primary outcome was safety. RESULTS: Of the 96 randomised and treated subjects, 85 completed the trial (n=27, 24, 22 and 23 for pooled placebo and MOR103 0.3, 1.0 and 1.5 mg/kg, respectively). Treatment emergent adverse events (AEs) in the MOR103 groups were mild or moderate in intensity and generally reported at frequencies similar to those in the placebo group. The most common AE was nasopharyngitis. In two cases, AEs were classified as serious because of hospitalisation: paronychia in a placebo subject and pleurisy in a MOR103 0.3 mg/kg subject. Both patients recovered fully. In exploratory efficacy analyses, subjects in the MOR103 1.0 and 1.5 mg/kg groups showed significant improvements in Disease Activity Score-28 scores and joint counts and significantly higher European League Against Rheumatism response rates than subjects receiving placebo. MOR103 1.0 mg/kg was associated with the largest reductions in disease activity parameters. CONCLUSIONS: MOR103 was well tolerated and showed preliminary evidence of efficacy in patients with active RA. The data support further investigation of this monoclonal antibody to GM-CSF in RA patients and potentially in those with other immune-mediated inflammatory diseases. TRIAL REGISTRATION NUMBER: NCT01023256 BMJ Publishing Group 2015-06 2014-02-17 /pmc/articles/PMC4431325/ /pubmed/24534756 http://dx.doi.org/10.1136/annrheumdis-2013-204816 Text en 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 This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Clinical and Epidemiological Research Behrens, Frank Tak, Paul P Østergaard, Mikkel Stoilov, Rumen Wiland, Piotr Huizinga, Thomas W Berenfus, Vadym Y Vladeva, Stoyanka Rech, Juergen Rubbert-Roth, Andrea Korkosz, Mariusz Rekalov, Dmitriy Zupanets, Igor A Ejbjerg, Bo J Geiseler, Jens Fresenius, Julia Korolkiewicz, Roman P Schottelius, Arndt J Burkhardt, Harald MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial |
title | MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial |
title_full | MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial |
title_fullStr | MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial |
title_full_unstemmed | MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial |
title_short | MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial |
title_sort | mor103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase ib/iia randomised, double-blind, placebo-controlled, dose-escalation trial |
topic | Clinical and Epidemiological Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431325/ https://www.ncbi.nlm.nih.gov/pubmed/24534756 http://dx.doi.org/10.1136/annrheumdis-2013-204816 |
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