Tofacitinib Uptake by Patient-Derived Intestinal Organoids Predicts Individual Clinical Responsiveness

Clinicians lack guidance in selecting the optimal therapy for an individual with ulcerative colitis (UC). Tofacitinib, a Janus kinase (JAK) inhibitor indicated for moderate to severe UC refractory to antitumor necrosis factor (TNF) therapy, is associated with >30% and 25% primary and secondary nonresponse rates, respectively. 1 Sandborn W.J. et al. Clin Gastroenterol Hepatol. 2022; 20: 1821-1830.e3 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Intestinal organoids can recreate disease-relevant events by retaining properties associated with an individual donor. 2 Matsuzawa-Ishimoto et al. Blood. 2020; 135: 2388-2401 Crossref PubMed Scopus (0) Google Scholar To test the hypothesis that patient-derived organoids can be applied toward predicting clinical responsiveness, we prospectively enrolled and monitored 48 patients initiating tofacitinib for UC. At week 24, 37.5% comprised responders (RPs) and 56.3% were partial responders (PRPs) or nonresponders (NRPs) (Supplementary Table 1, Supplementary Table 2, Supplementary Table 3).