SAT0260 Biomarkers Associated with Rheumatoid Arthritis Disease Activity Including Joint Damage Correlate with Changes in Clinical Response in Subjects Treated with Mavrilimumab at Doses above 10 Mg

Background Mavrilimumab is a human monoclonal antibody targeting the alpha subunit of GM-CSF receptor and was recently evaluated in RA subjects in a phase 2a study (EARTH). Results reported from the European (EU) cohort demonstrated that mavrilimumab shows activity in subjects with moderate to severe RA (Burmester et al. 2013). Here, we describe final data from EARTH comparing results in the EU and Japanese (JA) cohorts. Objectives Biomarker (BM) assessments were performed to elucidate mechanistic aspects of mavrilimumab. Methods Mavrilimumab (10, 30, 50 or 100 mg) or placebo was administered SC every other week to subjects with moderate/severe RA (DAS28 >3.2) on stable methotrexate for 12 weeks followed by a 12 week drug free follow up period. A multi-biomarker disease activity (MBDA) score was calculated using the validated Vectra ®DA algorithm and used to track the effect of the drug on disease activity over time. An additional multi-BM-based algorithm (MBSD) was used to assess the impact of mavrilimumab on markers known to be associated with progressive joint damage. The relative ability of different mavrilimumab doses, over time, to saturate GM-CSF receptors in whole blood was examined by flow cytometry using receptor occupancy assay (ROA) in the EU cohorts. Results In the EARTH study, the primary endpoint (DAS28-CRP reduction ≥1.2 at Week 12) was met. Improvements were seen as early as week 2 and persisted through the 12 week follow up. The MBDA score decreased significantly as early as day 8 (p