A personalised taper-to-target strategy with adalimumab in Crohn's disease

Abstract

In The Lancet Gastroenterology & Hepatology, Reinier C A van Linschoten and colleagues report the results of the LADI trial. 1 van Linschoten RCA Jansen FM Pauwels RWM et al. Increased versus conventional adalimumab dose interval for patients with Crohn's disease in stable remission (LADI): a pragmatic, open-label, non-inferiority, randomised controlled trial. Lancet Gastroenterol Hepatol. 2023; (published online Jan 31.)https://doi.org/10.1016/S2468-1253(22)00434-4 Google Scholar This trial is an excellent opportunity to explore adalimumab exposure–response relationships in patients with Crohn's disease. Surprisingly, no population pharmacokinetic–pharmacodynamic model of adalimumab in patients with Crohn's disease has been published since the approval of the type II variation by the European Medicines Agency in 2007. However, a pharmacokinetic–pharmacodynamic model was developed by marketing authorisation holder AbbVie, describing the temporal relation between adalimumab dose, adalimumab serum concentrations, and the Crohn's Disease Activity Index (CDAI). 2 European Medicines AgencyScientific discussion Humira—emea/h/c/481-482/ii/33. https://www.ema.europa.eu/en/documents/scientific-discussion-variation/humira-h-c-481-ii-33-epar-scientific-discussion-variation_en.pdfDate: 2007 Date accessed: January 15, 2023 Google Scholar Unfortunately, the model code was not shared, preventing model-informed design of the LADI trial through simulating dose-tapering scenarios and their effect on disease severity. 3 Bauer RJ Hooker AC Mentre F Tutorial for $DESIGN in NONMEM: clinical trial evaluation and optimization. CPT Pharmacometrics Syst Pharmacol. 2021; 10: 1452-1465 Crossref PubMed Scopus (0) Google Scholar Increased versus conventional adalimumab dose interval for patients with Crohn's disease in stable remission (LADI): a pragmatic, open-label, non-inferiority, randomised controlled trialThe individual benefit of increasing adalimumab dose intervals versus the risk of disease recurrence is a trade-off that should take patient preferences regarding medication and the risk of a flare into account. Full-Text PDF