Phase 3 induction study results show that the drug achieved a positive endoscopic response at week 12
AbbVie has announced positive top-line results from U-EXCEED, a phase 3 induction study, showing that upadacitinib (45 mg once daily) achieved both primary endpoints of clinical remissionand endoscopic responseat week 12.
The U-EXCEED study enrolled patients with moderate to severe Crohn disease who had an inadequate response or were intolerant to biologic therapy, with more than 60% having not had successful treatment using 2 or more biologics. "The data from this first phase 3 induction study in Crohn's disease suggest upadacitinib may help address the needs of patients suffering from this disease, as demonstrated in stringent endpoints such as endoscopic response," Michael Severino, MD, vice chairman and president of AbbVie, said in a statement. "We continue to leverage our expertise in IBD by driving research and development that help shape the IBD landscape and elevate standards of care for patients.”
In U-EXCEED, clinical remission was 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 the CDAI at week 12 compared with a placebo (39%, versus 21%; p<0.0001).1 Similar results were seen with clinical remission per SF/AP (40% in upadacitinib-treated patients versus 14% in placebo-treated patients; p<0.0001).1 In this study, all patients were also evaluated for improvement in the intestinal mucosa by endoscopy.1 At week 12, a significantly greater proportion of patients treated with upadacitinib 45 mg achieved endoscopic response compared with the placebo group (35% versus 4%; p<0.0001).1
Among individuals who took corticosteroids at baseline, a higher portion of individuals receiving upadacitinib at the 45-mg dose achieved steroid-free clinical remission at week 12, while a significant portion of those taking upadacitinib also achieved early symptom improvement at week 2 and at clinical remission at week 4.
"These results demonstrate upadacitinib's potential to achieve endoscopic response and clinical remission, including steroid-free clinical remission, at 12 weeks in patients living with Crohn's disease,” Jean-Frederic Colombel, MD, professor of medicine and director of Inflammatory Bowel Disease Center at the Icahn School of Medicine in Mount Sinai, said in the statement.
The safety profile of upadacitinib was consistent with previous studies across indications, and no new safety risks were observed.
The most common adverse event (AE) was nasopharyngitis for those taking upadacitinib and exacerbation of Crohn disease for those on the placebo, with serious AEs occurring in 9.3% of individuals in the upadacitinib 45-mg group and 9.9% of those in the placebo group.
The rate of serious infections was 2.8% for those treated with upadacitinib 45 mg and 1.8% for those on the placebo.
All events of herpes zoster were nonserious and reported in the upadacitinib group only, comprising 1.5% of individuals.
There was 1 case of adjudicated gastrointestinal perforation in the upadacitinib group.
An additional 207 individuals received upadacitinib 45 mg at week 12, and there were 2 other cases of adjudicated gastrointestinal perforation reported in that group.
The safety profile remained consistent for the 207 individuals.
Upadacitinib (RINVOQ®) achieved primary and key secondary endpoints in first phase 3 induction study in patients with Crohn's disease. AbbVie. News release. December 6, 2021. Accessed December 6, 2021. https://news.abbvie.com/article_display.cfm?article_id=12381