Nintedanib and ischemic colitis: Signal assessment with the integrated use of two types of real-world evidence, spontaneous reports of suspected adverse drug reactions, and observational data from large health-care databases.

PURPOSE: Statistical screening of Vigibase, the global database of individual case safety reports, highlighted an association between the MedDRA Preferred Term (PT) "colitis" and nintedanib. Nintedanib is a protein kinase inhibitor authorized in accelerated regulatory procedures for the treatment of idiopathic pulmonary fibrosis (IPF). The aim of this report is to describe the integration of two types of real-world evidence, spontaneous reports of adverse drug reactions (ADR), and observational health data (OHD) in the assessment of a post-authorization safety signal of ischemic colitis. METHODS: Assessment of the statistical signal of "nintedanib - colitis" was undertaken using data from VigiBase, OHD from the Observational Heath Data Sciences and Informatics (OHDSI) collaborative, published literature, and openly available regulatory documents. Evidence synthesis was performed to support Bradford Hill criteria in causality assessment. RESULTS: Evidence for strength of association, specificity, consistency, and analogy was found upon review of the case series. OHD was used to calculate incidence rates of colitis in new users of nintedanib across multiple populations, supportive of consistency, and further evidence for strength of association. Literature review identified support for biological plausibility and analogy. Signal assessment was supplemented with characterization of real-world users and exploration of potential risk factors using OHD. CONCLUSIONS: An integrated approach using two forms of real-world data, spontaneous reports of ADRs and data from observational databases allowed a comprehensive and efficient signal assessment of nintedanib and colitis. Further exploration of the complementary use of real-time OHD in signal assessment could inform more efficient approaches to current signal management practices.