AbbVie today announced positive top-line results from U-EXCEL, a Phase 3 induction study, showing upadacitinib (45 mg once daily) achieved both primary endpoints of clinical remissiona,b and endoscopic responsec at week 12.1 U-EXCEL is the second of two Phase 3 induction studies to evaluate the safety and efficacy of upadacitinib in adults with moderate to severe Crohn’s disease who had an inadequate response or were intolerant to conventional or biologic therapy.1
U-EXCEL included the same primary and key secondary endpoints as U-EXCEED, with clinical remission measured by the Crohn’s Disease Activity Index (CDAI) and by the patient-reported symptoms of stool frequency/abdominal pain (SF/AP).1 A significantly greater proportion of patients treated with a 12-week induction regimen of upadacitinib 45 mg daily achieved clinical remission per CDAI at week 12 compared to placebo (49 percent versus 29 percent; p<0.0001).1 Similar results were observed with clinical remission per SF/AP (51 percent in upadacitinib-treated patients versus 22 percent in placebo-treated patients; p<0.0001).1 At week 12, a significantly greater proportion of patients treated with upadacitinib 45 mg achieved endoscopic response compared to the placebo group (46 percent versus 13 percent; p<0.0001).1
Consistent with results from the U-EXCEED induction study, a significantly higher proportion of patients receiving upadacitinib 45 mg also achieved steroid-free clinical remissiond per CDAI and per SF/AP compared to placebo at week 12 among patients taking corticosteroids at baseline.1 Early symptom improvement measured by CR-100 (defined as reduction of CDAI ≥100 points from baseline) at week two as well as clinical remission at week four were also achieved by a significantly higher proportion of patients receiving upadacitinib 45 mg.1
During the 12-week, double-blind, placebo-controlled period, the safety profile of upadacitinib 45 mg was consistent with the safety profile observed in previous studies across indications, with no new safety risks observed.1 The most common adverse events were acne and anemia in the upadacitinib 45 mg group.1 Serious adverse events occurred in 6.9 percent of patients in the upadacitinib 45 mg group compared to 6.8 percent of patients in the placebo group.1 Rates of serious infections were 1.1 percent in patients treated with upadacitinib 45 mg and 1.7 percent in those who received placebo.1 Herpes zoster was reported in 2.9 percent of patients treated with upadacitinib 45 mg, all cases were nonserious.1 There were no cases of adjudicated gastrointestinal perforation or death during the placebo-controlled period.1 One case of adjudicated major cardiovascular event (MACE) was reported in the placebo group.1
Patients who were on upadacitinib 45 mg and did not achieve clinical response at week 12 were included in an additional 12-week treatment cohort with upadacitinib 30 mg.1 In this cohort, one patient died of COVID-19.1 Patients who were on placebo and did not achieve clinical response at week 12 were included in a 12-week treatment cohort with upadacitinib 45 mg.1 Among these patients, there was one case of adjudicated gastrointestinal perforation.1
In U-EXCEL, no treatment-emergent cases of adjudicated MACE, malignancy or adjudicated venous thromboembolic event were reported in patients on upadacitinib treatment.1
Full results from the U-EXCEL study will be presented at upcoming medical conferences and published in a peer-reviewed medical journal. Top-line results from the Phase 3 portion of the first induction study, U-EXCEED, were announced in December 2021 and the maintenance study for both is ongoing. Use of upadacitinib in Crohn’s disease is not approved and its safety and efficacy have not been evaluated by regulatory authorities.
dSteroid-free clinical remission is defined as clinical remission (per CDAI <150, or per SF/AP with average daily SF ≤2.8 and not worse than baseline and average daily AP score ≤1 and not worse than baseline) and discontinuation of corticosteroid use among patients taking corticosteroids at baseline.