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In Crohn's disease-affected individuals, Upadacitinib shows significant efficacy in inducing and sustaining clinical remission and endoscopic response.
In phase 3 trials, Upadacitinib exhibited superior effectiveness over placebo in inducing and maintaining clinical remission and endoscopic responses in people battling Crohn's illness. Researchers aimed to evaluate the impact of an orally administered selective Janus kinase (JAK) inhibitor in the treatment of moderate-to-severe Crohn's disease.
In two separate phase 3 induction trials, namely U-EXCEL and U-EXCEED, individuals diagnosed with moderate-to-severe Crohn's disease were randomized to get either Upadacitinib (45 mg) or a placebo (in a ratio of 2:1) once a day for a duration of 12 weeks. Among those patients who exhibited a positive clinical response to Upadacitinib induction therapy, a subsequent trial called U-ENDURE was conducted for maintenance, wherein participants were randomized to get either 15 mg of Upadacitinib, 30 mg of Upadacitinib, or a placebo (in a ratio of 1:1:1) once daily over a span of 52 weeks.
Clinical remission, indicated as a Crohn's Disease Activity Index score of <150 (on a range of 0 to 600, where greater scores indicated more severity of illness), and endoscopic response, characterized as a drop of more than 50% from baseline in the Simple Endoscopic Score for Crohn's Disease (SES-CD; on a range of 0 to 56, where greater scores indicate more severity of illness) in the induction trial (or a decline of at least 2 points from baseline for those having an SES-CD of 4 at baseline) were the major outcomes assessed at week twelve (induction) and week fifty-two (maintenance).
The study included a total of 526 volunteers in U-EXCEL, 495 subjects in U-EXCEED, and 502 patients in U-ENDURE. The results revealed a significantly higher proportion of patients who were administered 45 mg Upadacitinib compared to those given a placebo, achieving clinical remission (49.5% vs. 29.1% in U-EXCEL; 38.9% vs. 21.1% in U-EXCEED) and an endoscopic response (45.5% vs. 13.1% in U-EXCEL; 34.6% vs. 3.5% in U-EXCEED).
In U-ENDURE, a greater proportion of people attained clinical remission at week 52 using 15 mg Upadacitinib (37.3%) or 30 mg Upadacitinib (47.6%) in comparison with placebo recipients (15.1%). Notably, a greater proportion achieved an endoscopic response using 15 mg Upadacitinib (27.6%) or 30 mg Upadacitinib (40.1%) compared to placebo recipients (7.3%). Of importance, the incidence of herpes zoster infections was higher in the 45 mg and 30 mg Upadacitinib arms compared to their respective placebo arms. On the other hand, hepatic illness and neutropenia were highly prevalent in the 30 mg Upadacitinib arm compared to other maintenance arms.
Additionally, perforations in the intestine were observed in four people receiving 45 mg of Upadacitinib and in one person each receiving 30 mg or 15 mg of Upadacitinib. In patients diagnosed with moderate-to-severe Crohn's disease, the effectiveness of Upadacitinib induction and maintenance treatment surpassed that of the placebo.
New England Journal of Medicine
Upadacitinib Induction and Maintenance Therapy for Crohn's Disease
Edward V Loftus Jr et al.
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