Higher Drug Exposure During the First 24 Weeks of Ustekinumab Treatment Is Associated With Endoscopic Remission in Crohn's Disease.

Over the past 2 decades, the treatment of Crohn’s disease (CD) has significantly changed with the introduction of biologicals targeting key inflammatory players. Ustekinumab is a human monoclonal antibody directed against the common p40 subunit of interleukin-12 and interleukin-23, cytokines involved in the immune cascade of chronic immune-mediated inflammatory diseases. 1 Benson J.M. et al. mAbs. 2011; 3: 535-545 Crossref PubMed Scopus (183) Google Scholar As with all biologicals, nonresponse or loss of response to treatment can occur when treating patients with CD with ustekinumab. The UNITI registration trials and subsequent real-world studies reported clinical response rates of around 35%–55% after ustekinumab induction therapy. 2 Feagan B.G. et al. N Engl J Med. 2016; 375: 1946-1960 Crossref PubMed Scopus (1038) Google Scholar ,3 Macaluso F.S. et al. Expert Opin Biol Ther. 2020; 20: 193-203 Crossref PubMed Scopus (28) Google Scholar Inadequate response to treatment can be associated with underexposure to the drug. Several studies have demonstrated the relationship between ustekinumab concentrations and clinical, biologic, or endoscopic response, indicating the potential usefulness of therapeutic drug monitoring to guide clinical decision-making. 4 Verstockt B. et al. J Crohns Colitis January. 2019; 13: 864-872 Crossref PubMed Scopus (65) Google Scholar , 5 Battat R. et al. Clin Gastroenterol Hepatol. 2017; 15: 1427-1434 Abstract Full Text Full Text PDF PubMed Scopus (149) Google Scholar , 6 Soufflet N. et al. Clin Gastroenterol Hepatol. 2019; 17: 2610-2612 Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Anti–tumor necrosis factor drug concentrations measured during induction are associated with long-term outcomes. 7 Singh N. et al. Inflamm Bowel Dis. 2014; 20: 1708-1713 Crossref PubMed Scopus (123) Google Scholar ,8 Verstockt B. et al. Aliment Pharmacol Ther August. 2018; 48: 731-739 Crossref PubMed Scopus (57) Google Scholar For ustekinumab, however, the time point at which the drug concentration is most informative for long-term outcome is unknown. In this study, we evaluated the exposure-response relationship of ustekinumab throughout the first 24 weeks of treatment in patients with CD and investigated the time points at which ustekinumab levels could identify patients achieving endoscopic remission.