Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis

Gerd R Burmester, Michael E Weinblatt, Iain B McInnes, Duncan Porter, Olga Barbarash, Mykola Vatutin, Istvan Szombati, Ehsanollah Esfandiari, Matthew A Sleeman, Christopher D Kane, Guy Cavet, Bing Wang, Alex Godwood, Fabio Magrini, EARTH Study Group, Gerd R Burmester, Michael E Weinblatt, Iain B McInnes, Duncan Porter, Olga Barbarash, Mykola Vatutin, Istvan Szombati, Ehsanollah Esfandiari, Matthew A Sleeman, Christopher D Kane, Guy Cavet, Bing Wang, Alex Godwood, Fabio Magrini, EARTH Study Group

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.

Keywords: Disease Activity; Rheumatoid Arthritis; Treatment.

Figures

Figure 1
Figure 1
Patient disposition (ITT population).
Figure 2
Figure 2
(A−E) Efficacy according to DAS-28 and Health Assessment Questionnaire Disability Index (HAQ-DI) assessments (ITT population). (A) DAS28-CRP responses by treatment group at week 12. (B) Mean DAS28-CRP by visit. (C) Time to onset of DAS28-CRP

Figure 3

Efficacy according to American College…

Figure 3

Efficacy according to American College of Rheumatology (ACR) assessment (ITT population). (A) ACR…

Figure 3
Efficacy according to American College of Rheumatology (ACR) assessment (ITT population). (A) ACR responses by treatment group at week 12. (B) ACR20 responses by visit. (C) ACR50 responses by visit. (D) ACR70 responses by visit.
Figure 3
Figure 3
Efficacy according to American College of Rheumatology (ACR) assessment (ITT population). (A) ACR responses by treatment group at week 12. (B) ACR20 responses by visit. (C) ACR50 responses by visit. (D) ACR70 responses by visit.

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