PMID- 24534756 OWN - NLM STAT- MEDLINE DCOM- 20150728 LR - 20220311 IS - 1468-2060 (Electronic) IS - 0003-4967 (Print) IS - 0003-4967 (Linking) VI - 74 IP - 6 DP - 2015 Jun TI - 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. PG - 1058-64 LID - 10.1136/annrheumdis-2013-204816 [doi] AB - 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. CI - 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. FAU - Behrens, Frank AU - Behrens F AD - CIRI/Division of Rheumatology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany Department of Translational Medicine and Pharmacology, Fraunhofer Institute IME, Frankfurt am Main, Germany. FAU - Tak, Paul P AU - Tak PP AD - Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands GlaxoSmithKline, Stevenage, UK University of Cambridge, Cambridge, UK. FAU - Ostergaard, Mikkel AU - Ostergaard M AD - Copenhagen Center for Arthritis Research, Center for Rheumatology and Spinal Diseases, Copenhagen University Hospital Glostrup, Glostrup, Denmark. FAU - Stoilov, Rumen AU - Stoilov R AD - University Hospital (MHAT) St Ivan Rilski, Sofia, Bulgaria. FAU - Wiland, Piotr AU - Wiland P AD - Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland. FAU - Huizinga, Thomas W AU - Huizinga TW AD - Department of Rheumatology, Leiden University Medic al Center, Leiden, The Netherlands. FAU - Berenfus, Vadym Y AU - Berenfus VY AD - Regional Clinical Hospital, Donetsk, Ukraine. FAU - Vladeva, Stoyanka AU - Vladeva S AD - Second Internal Clinic UMHAT Stara Zagora, Stara Zagora, Bulgaria. FAU - Rech, Juergen AU - Rech J AD - University of Erlangen-Nuremberg, Erlangen, Germany. FAU - Rubbert-Roth, Andrea AU - Rubbert-Roth A AD - Med Clinic I, University of Cologne, Cologne, Germany. FAU - Korkosz, Mariusz AU - Korkosz M AD - Malopolskie Centrum Medyczne, Krakow, Poland. FAU - Rekalov, Dmitriy AU - Rekalov D AD - Zaporizhzhia Regional Hospital, Zaporozhe, Ukraine. FAU - Zupanets, Igor A AU - Zupanets IA AD - National University of Pharmacy, Kharkiv, Ukraine. FAU - Ejbjerg, Bo J AU - Ejbjerg BJ AD - Department of Rheumatology, Hospital at Slagelse, Slagelse, Denmark. FAU - Geiseler, Jens AU - Geiseler J AD - Asklepios Clinic Munich-Gauting, Gauting, Germany. FAU - Fresenius, Julia AU - Fresenius J AD - Asklepios Clinic Munich-Gauting, Gauting, Germany. FAU - Korolkiewicz, Roman P AU - Korolkiewicz RP AD - MorphoSys AG, Martinsried/Planegg, Germany. FAU - Schottelius, Arndt J AU - Schottelius AJ AD - MorphoSys AG, Martinsried/Planegg, Germany. FAU - Burkhardt, Harald AU - Burkhardt H AD - CIRI/Division of Rheumatology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany Department of Translational Medicine and Pharmacology, Fraunhofer Institute IME, Frankfurt am Main, Germany. LA - eng SI - ClinicalTrials.gov/NCT01023256 PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20140217 PL - England TA - Ann Rheum Dis JT - Annals of the rheumatic diseases JID - 0372355 RN - 0 (Adrenal Cortex Hormones) RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antirheumatic Agents) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - Y8127R3VCH (Otilimab) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM MH - Adrenal Cortex Hormones/therapeutic use MH - Adult MH - Aged MH - Antibodies, Monoclonal/*administration & dosage/adverse effects MH - Antibodies, Monoclonal, Humanized MH - Antirheumatic Agents/*administration & dosage/adverse effects/therapeutic use MH - Arthritis, Rheumatoid/*drug therapy MH - Double-Blind Method MH - Drug Therapy, Combination MH - Female MH - Granulocyte-Macrophage Colony-Stimulating Factor/*antagonists & inhibitors MH - Humans MH - Male MH - Methotrexate/therapeutic use MH - Middle Aged MH - Nasopharyngitis/chemically induced MH - Pleurisy/chemically induced MH - Treatment Outcome PMC - PMC4431325 OTO - NOTNLM OT - DAS28 OT - DMARDs (biologic) OT - Rheumatoid Arthritis OT - Treatment EDAT- 2014/02/19 06:00 MHDA- 2015/07/29 06:00 PMCR- 2015/05/14 CRDT- 2014/02/19 06:00 PHST- 2013/10/24 00:00 [received] PHST- 2014/01/24 00:00 [accepted] PHST- 2014/02/19 06:00 [entrez] PHST- 2014/02/19 06:00 [pubmed] PHST- 2015/07/29 06:00 [medline] PHST- 2015/05/14 00:00 [pmc-release] AID - annrheumdis-2013-204816 [pii] AID - 10.1136/annrheumdis-2013-204816 [doi] PST - ppublish SO - Ann Rheum Dis. 2015 Jun;74(6):1058-64. doi: 10.1136/annrheumdis-2013-204816. Epub 2014 Feb 17.