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Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis
  1. Gerd R Burmester1,
  2. Michael E Weinblatt2,
  3. Iain B McInnes3,
  4. Duncan Porter4,
  5. Olga Barbarash5,
  6. Mykola Vatutin6,
  7. Istvan Szombati7,
  8. Ehsanollah Esfandiari8,12,
  9. Matthew A Sleeman8,
  10. Christopher D Kane9,15,
  11. Guy Cavet10,14,
  12. Bing Wang11,
  13. Alex Godwood8,
  14. Fabio Magrini8,13,
  15. for the EARTH Study Group
  1. 1Charité—University Medicine Berlin, Department of Rheumatology and Clinical Immunology Free University and Humboldt University, Berlin, Germany
  2. 2Division of Rheumatology, Immunology and Allergy Brigham and Women's Hospital, Boston, Massachusetts, USA
  3. 3Glasgow Biomedical Research Centre, Glasgow, UK
  4. 4Department of Rheumatology, Gartnavel General Hospital, Glasgow, UK
  5. 5SIH Kemerovo Regional Clinical Hospital, Kemerovo, Russian Federation
  6. 6Donetsk National Medical University named after M. Gorky, Donestsk, Ukraine
  7. 7Óbudai Egészségügyi Centrum, Budapest, Hungary
  8. 8MedImmune Ltd, Cambridge, UK
  9. 9MedImmune, LLC, Gaithersburg, Maryland, USA
  10. 10Crescendo Bioscience Inc., South San Francisco, California, USA
  11. 11MedImmune, LLC, Hayward, California, USA
  12. 12Imperial College, Division of Medicine, Immunology/Inflammation, London, UK
  13. 13Lilly Biotechnology Center, San Diego, California, USA
  14. 14Kaggle, San Francisco, Califorinia, USA
  15. 15US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA
  1. Correspondence to Dr Gerd R Burmester,  Charité—University Medicine Berlin, Free University and Humboldt University Berlin, Charitéplatz 1, Berlin 10117, Germany; Gerd.Burmester{at}charite.de

Abstract

Objectives Mavrilimumab, a human monoclonal antibody targeting the alpha subunit of the granulocyte-macrophage colony-stimulating factor receptor, was evaluated in a phase 2 randomised, double-blind, placebo-controlled study to investigate efficacy and safety in subjects with rheumatoid arthritis (RA).

Methods Subcutaneous mavrilimumab (10 mg, 30 mg, 50 mg, or 100 mg) or placebo was administered every other week for 12 weeks in subjects on stable background methotrexate therapy. The primary endpoint was the proportion of subjects achieving a ≥1.2 decrease from baseline in Disease Activity Score (DAS28-CRP) at week 12.

Results 55.7% of mavrilimumab-treated subjects met the primary endpoint versus 34.7% placebo (p=0.003) at week 12; for the 10 mg, 30 mg, 50 mg, and 100 mg groups, responses were 41.0% (p=0.543), 61.0% (p=0.011), 53.8% (p=0.071), and 66.7% (p=0.001) respectively. Response rate differences from placebo were observed at week 2 and increased throughout the treatment period. The 100 mg dose demonstrated a significant effect versus placebo on DAS28-CRP<2.6 (23.1% vs 6.7%, p=0.016), all categories of the American College of Rheumatology (ACR) criteria (ACR20: 69.2% vs 40.0%, p=0.005; ACR50: 30.8% vs 12.0%, p=0.021; ACR70: 17.9% vs 4.0%, p=0.030), and the Health Assessment Questionnaire Disability Index (−0.48 vs −0.25, p=0.005). A biomarker-based disease activity score showed a dose-dependent decrease at week 12, indicating suppression of disease-related biological pathways. Adverse events were generally mild or moderate in intensity. No significant hypersensitivity reactions, serious or opportunistic infections, or changes in pulmonary parameters were observed.

Conclusions Mavrilimumab induced rapid clinically significant responses in RA subjects, suggesting that inhibiting the mononuclear phagocyte pathway may provide a novel therapeutic approach for RA.

  • Rheumatoid Arthritis
  • Treatment
  • Disease Activity

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