Revisiting Therapies for Atopic Dermatitis that Failed Clinical Trials.

Multiple pathways contribute to the pathogenesis of atopic dermatitis (AD), and various targeted topical, biologic, and oral systemic agents have subsequently been developed. This review examines the mechanism of action and study designs of agents that have failed trials for AD to identify lessons that may shed light on reasons for their failure. Clinicaltrials.gov was searched for completed, placebo-controlled phase II and III studies assessing agents for AD that did not meet the primary endpoint, specifically reduction of AD severity. PubMed was then searched for further data on the agents identified with known mechanism of actions. Only phase II trials met inclusion criteria. Analyses of the mechanisms of action, study design, and patient demographics of the failed clinical trials for the following agents are presented: apremilast and roflumilast (PDE-4 inhibitors), fevipiprant and temapiprant (CRTH2 inhibitors), and tezepelumab and ustekinumab (monoclonal antibodies). Agents that did not meet their trial endpoints for AD may still hold therapeutic value in certain subpopulation groups or other diseases. Validating phase II trials based off subgroup analyses from previous trials may be warranted as our understanding of the pathophysiology of AD continues to grow.