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.
abstract: OBJECTIVE
  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.
  
  
  BACKGROUND
  NCT01023256.
authors.affiliation: 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.
authors.forename: Frank
authors.initials: F
authors.lastname: Behrens
authors.affiliation: Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands GlaxoSmithKline, Stevenage, UK University of Cambridge, Cambridge, UK.
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.affiliation: Copenhagen Center for Arthritis Research, Center for Rheumatology and Spinal Diseases, Copenhagen University Hospital Glostrup, Glostrup, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Østergaard
authors.affiliation: University Hospital (MHAT) St Ivan Rilski, Sofia, Bulgaria.
authors.forename: Rumen
authors.initials: R
authors.lastname: Stoilov
authors.affiliation: Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Wiland
authors.affiliation: Department of Rheumatology, Leiden University Medic al Center, Leiden, The Netherlands.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Huizinga
authors.affiliation: Regional Clinical Hospital, Donetsk, Ukraine.
authors.forename: Vadym Y
authors.initials: VY
authors.lastname: Berenfus
authors.affiliation: Second Internal Clinic UMHAT Stara Zagora, Stara Zagora, Bulgaria.
authors.forename: Stoyanka
authors.initials: S
authors.lastname: Vladeva
authors.affiliation: University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Rech
authors.affiliation: Med Clinic I, University of Cologne, Cologne, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rubbert-Roth
authors.affiliation: Malopolskie Centrum Medyczne, Krakow, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Korkosz
authors.affiliation: Zaporizhzhia Regional Hospital, Zaporozhe, Ukraine.
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Rekalov
authors.affiliation: National University of Pharmacy, Kharkiv, Ukraine.
authors.forename: Igor A
authors.initials: IA
authors.lastname: Zupanets
authors.affiliation: Department of Rheumatology, Hospital at Slagelse, Slagelse, Denmark.
authors.forename: Bo J
authors.initials: BJ
authors.lastname: Ejbjerg
authors.affiliation: Asklepios Clinic Munich-Gauting, Gauting, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Geiseler
authors.affiliation: Asklepios Clinic Munich-Gauting, Gauting, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Fresenius
authors.affiliation: MorphoSys AG, Martinsried/Planegg, Germany.
authors.forename: Roman P
authors.initials: RP
authors.lastname: Korolkiewicz
authors.affiliation: MorphoSys AG, Martinsried/Planegg, Germany.
authors.forename: Arndt J
authors.initials: AJ
authors.lastname: Schottelius
authors.affiliation: 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.
authors.forename: Harald
authors.initials: H
authors.lastname: Burkhardt
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009304:Nasopharyngitis / Q000139:chemically induced; D010998:Pleurisy / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C000599766:Otilimab; D008727:Methotrexate
keywords: DAS28; DMARDs (biologic); Rheumatoid Arthritis; Treatment