Effectiveness and Safety of Upadacitinib for Crohn's Disease: Real-World Data From a Tertiary Center

Introduction: Upadacitinib (UPA) is a selective JAK-1 inhibitor approved for the treatment of rheumatoid arthritis (RA). Recently, the phase 2 CELEST trial showed that UPA induces endoscopic remission in Crohn’s disease (CD) patients at doses of 24mg twice daily and 24mg once daily. However, real world data are lacking. We describe the effectiveness and safety of UPA patients with CD at a tertiary center. Methods: We included patients with CD treated with UPA at _____ between 2019 and 2021. We retrospectively reviewed clinical, endoscopic, and histologic data to ascertain patient-reported subjective response and adverse event rates. Objective response was defined as any improvement in inflammatory markers, endoscopy, histology or imaging. Descriptive statistics and Wilcoxon signed rank test were performed. Results: Twelve patients with medically refractory disease (+/- joint involvement) were included: 9 women, 8 with ileo-colonic CD and 8 with fistulizing and/or penetrating CD. Most (67%) had perianal involvement and 83% had a history of bowel resection. All had prior exposure to biologics and 92% had extra-intestinal manifestations (Table 1). UPA was dosed at 15mg QD except in one patient who was started at 30mg QD and later transitioned to 15mg QD. Median treatment duration with UPA was 5.2 months (IQR 2.8–6.8) and 5 patients (42%) continued on therapy at the time of analysis. Subjectively, 25% reported improvement in their CD-related bowel symptoms and 33% in their joint pain. Four patients (33%) had objective evidence of response. There were no significant changes in routine hematologic and biochemical laboratory markers pre- and post-therapy (Figure 1). Adverse events resulting in treatment discontinuation were noted in 2 patients (1 fatigue and recurrent infections and 1 headache). Conclusion: In this cohort of medically-refractory patients with CD, treatment with UPA resulted in subjective and objective response in 25% and 33% of patients, respectively. To our knowledge, this is the first real-world report of UPA in patients with CD. Even at doses approved for RA that are considered lower than currently being studied for CD, UPA was associated with an overall favorable benefit/risk profile.Figure 1.: Percent Change in Median Lab Values Pre- and Post-Upadacitinib Therapy in Patients with CD.Table 1.: Demographic and Clinical Characteristics of Patients with CD Treated with Upadacitinib