- Loftus EV, et al. Efficacy and safety of upadacitinib induction therapy in patients with moderately to severely active Crohn´s Disease: results from a randomized phase 3 U-EXCEL study. OP192, UEG Week 2022, Vienna, Austria, 8–11 October.
Previously, the JAK 1 inhibitor upadacitinib has been shown to be effective in inducing clinical and endoscopic improvement, with an acceptable safety profile in the U-EXCEED study (NCT03345836). U-EXCEL (NCT03345849) is a second induction study in patients with moderately-to-severely active Crohn´s disease.
Primary endpoints of U-EXCEL at week 12 were clinical remission measured by the Crohn's Disease Activity Index (CDAI <150) and by the patient-reported symptoms of stool frequency/abdominal pain (SF/AP) and endoscopic response1. All patients must have failed or be intolerant to conventional or biologic therapy. By week 12, 88.0% of the placebo group (n=155) and 93.7% in the upadacitinib group (n = 328) completed the study. Almost half (45%) of the study population had already failed prior biologic therapy, in most cases a prior TNF-blocker.
A significantly higher percentage of patients treated with upadacitinib achieved the co-primary endpoints compared with placebo: 49.5% of patients treated with upadacitinib achieved CDAI <150 compared with 29.1% in the placebo group (P<0.0001). The SF/AP clinical remission (average daily stool frequency ≤2.8 and average daily abdominal pain ≤1 and neither worse at baseline) was 50.7% versus 22.2% (P<0.0001), for the patient and placebo group respectively. In addition, endoscopic response was significantly higher in upadacitinib-treated patients with a clinically relevant difference of 33% (P<0.0001).
“I believe that the achievement of endoscopic response in Crohn’s disease in almost half of the patients is a unique achievement of efficacy in an induction trial,” said Prof. Julian Panés (Hospital Clínic Barcelona, Spain). A significant proportion of patients treated with upadacitinib achieved clinical response as early as week 2 and clinical remission at week 4.
Among patients taking corticosteroids at baseline, a significantly higher proportion of patients receiving upadacitinib 45 mg achieved steroid-free clinical remission per CDAI and per SF/AP compared with placebo at week 12 (P<0.0001 vs placebo for each comparison). “Finally, as much as 28.9% of patients treated with upadacitinib achieved endoscopic remission at this early time point,” Prof. Panés pointed out.
Treatment-emergent adverse events were noted in 58.6% of placebo patients compared with 62.8% in the upadacitinib arm, but there was no difference in serious adverse events between the groups, and no deaths occurred. A higher proportion of patients in the placebo arm reported worsening of Crohn´s disease, whereas anaemia and acne were reported in 6.3% and 6.9% of the patients treated with upadacitinib, a class-related effect as Prof. Panés pointed out. Regarding adverse events of special interest, herpes zoster and anaemia were more frequent in the upadacitinib arm but there was no case of gastrointestinal perforation.