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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
  1. Frank Behrens1,2,
  2. Paul P Tak3,4,5,
  3. Mikkel Østergaard6,
  4. Rumen Stoilov7,
  5. Piotr Wiland8,
  6. Thomas W Huizinga9,
  7. Vadym Y Berenfus10,
  8. Stoyanka Vladeva11,
  9. Juergen Rech12,
  10. Andrea Rubbert-Roth13,
  11. Mariusz Korkosz14,
  12. Dmitriy Rekalov15,
  13. Igor A Zupanets16,
  14. Bo J Ejbjerg17,
  15. Jens Geiseler18,
  16. Julia Fresenius18,
  17. Roman P Korolkiewicz19,
  18. Arndt J Schottelius19,
  19. Harald Burkhardt1,2
  1. 1CIRI/Division of Rheumatology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany
  2. 2Department of Translational Medicine and Pharmacology, Fraunhofer Institute IME, Frankfurt am Main, Germany
  3. 3Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
  4. 4GlaxoSmithKline, Stevenage, UK
  5. 5University of Cambridge, Cambridge, UK
  6. 6Copenhagen Center for Arthritis Research, Center for Rheumatology and Spinal Diseases, Copenhagen University Hospital Glostrup, Glostrup, Denmark
  7. 7University Hospital (MHAT) St Ivan Rilski, Sofia, Bulgaria
  8. 8Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland
  9. 9Department of Rheumatology, Leiden University Medic al Center, Leiden, The Netherlands
  10. 10Regional Clinical Hospital, Donetsk, Ukraine
  11. 11Second Internal Clinic UMHAT Stara Zagora, Stara Zagora, Bulgaria
  12. 12University of Erlangen-Nuremberg, Erlangen, Germany
  13. 13Med Clinic I, University of Cologne, Cologne, Germany
  14. 14Malopolskie Centrum Medyczne, Krakow, Poland
  15. 15Zaporizhzhia Regional Hospital, Zaporozhe, Ukraine
  16. 16National University of Pharmacy, Kharkiv, Ukraine
  17. 17Department of Rheumatology, Hospital at Slagelse, Slagelse, Denmark
  18. 18Asklepios Clinic Munich-Gauting, Gauting, Germany
  19. 19MorphoSys AG, Martinsried/Planegg, Germany
  1. Correspondence to Professor Dr Harald Burkhardt, Division of Rheumatology/CIRI, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, Frankfurt/Main D 60590, Germany; Harald.Burkhardt{at}kgu.de

Abstract

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

  • Rheumatoid Arthritis
  • DMARDs (biologic)
  • DAS28
  • Treatment

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