Evolution of the inclusion/exclusion criteria and primary endpoints in pivotal trials of biologics and small oral molecules for the treatment of psoriasis

Introduction: Primary endpoints and inclusion/exclusion criteria of biologics and small oral molecules for psoriasis treatment have been evolving due to a better understanding of the pathogenesis and potential risks. Areas covered: We analyzed the designs of key phase 3 pivotal trials of all biologics and small oral molecules approved for moderate to severe plaque psoriasis from published data on the ClinicalTrials.gov website and literature in the PubMed database. Alefacept, efalizumab, anti-tumor necrosis factors, anti-interleukin (IL)-12/IL-23, anti-IL-17 and anti-IL-23 inhibitors were discussed chronologically. Small oral molecules including tofacitinib and apremilast were also reviewed. Expert opinion: The primary endpoints of trials of biologics have been raised progressively and psoriasis area and severity index (PASI) 100 can now be readily achievable by the recent biologics. For safety, 5-year observation periods have become a gold standard after the report of progressive multifocal leukoencephalopathy after efalizumab. Also, the need for tuberculosis (TB) prophylaxis has also been relaxed in one trial of risankizumab. Small oral molecules are the future of affordable effective treatment for psoriasis, but the safety concerns must be overcome as reflected by their more stringent exclusion criteria. More biologic switch data and inclusion of patients previously excluded, e.g. viral hepatitis, are still needed.