Therapeutic protein-drug interactions: plausible mechanisms and assessment strategies

Over the last three decades, therapeutic proteins have played an increasingly important role in pharmacotherapy. Owing to an expected significant increase in the coadministration of biotherapeutics with established pharmacotherapy regimens or even with other biotherapeutic agents, there is an increasing likelihood for the occurrence of clinically relevant drug interactions, so called therapeutic protein-drug interactions (TP-DIs). Areas covered: Our current understanding of TP-DIs and recent collaborations among industry, academia and regulatory agencies are reviewed in this article. Although most of the observed TP-DIs are mediated by disease states, immune status, and/or target physiology, TP-DI assessments are still done empirically. Plausible mechanisms of major TP-DIs involving therapeutic proteins (primarily monoclonal antibodies), either as victims or as perpetrators, are proposed, with mechanism-based strategies and assessment approaches to better evaluate their propensity are recommended. Expert opinion: Our current understanding of the mechanisms of TP-DIs is in its infancy. Much of the basic research needs to be conducted to verify existing TP-DI hypotheses or help predict and manage potential ones, whose efforts are not considered trivial and may be better achieved through close collaborations among scientists from academia, industry, and regulatory agencies.