The therapeutic options for treatment of rheumatic diseases have grown and now include a variety of inflammatory pathway inhibitors, with diverse mechanisms, but having both shared and unique side effects. Understanding side effect mechanisms is important for guiding patient treatment choices and also for developing improved next generation therapies. We have successfully employed high throughput primary human cell-based models of tissue and disease, BioMAP Systems, to study failed and approved drugs and have previously identified in vitro activities that correlate with certain side effects. Here we compare the activity profiles of adalimumab (TNF inhibitor), MTX and anakinra (IL1RA) to test if activities can be correlated with differences in efficacy or safety.
METHODS: A panel of 12 BioMAP systems, including mono- and co-cultures of vascular, immune, and tissue cell types were used to generate profiles of anakinra, adalimumab, and MTX. Changes in protein-based and clinically relevant endpoints (biomarkers, including inflammatory, immune, tissue remodeling and hemostasis-related endpoints) as well as other cellular events (e.g., proliferation, cell cytotoxicity) were evaluated. For select activities, a comparison to a large reference database of approved and failed drugs, experimental chemicals, and other
agents, was performed to elucidate potential mechanisms.