AbbVie Announces Positive Results for Upadacitinib in Patients With Crohn Disease

The drug has achieved both primary endpoints of clinical remission and endoscopic response at week 12 compared with the placebo, the company says.

AbbVie announced positive top-line results from U-EXCEL, a phase 3 induction study, showing that Crohn disease medication upadacitinib, at the 4- mg strength, achieved both primary endpoints of clinical remission and endoscopic response at week 12, according to a company statement.

U-EXCEL is the second 2 phase 3 induction study that evaluating the efficacy and safety of upadacitinib in adults with moderate to severe Crohn disease who had an inadequate response or were intolerant to biologic or conventional therapy.

"It is impressive to see the meaningful response that was achieved in this study in patients with moderate to severe Crohn's disease who have had inadequate response to an immunosuppressant or a biologic," Edward Loftus, MD, professor of medicine in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minnesota, said in the statement. "These results suggest that upadacitinib may help patients who are unable to control their disease, including symptoms and intestinal inflammation, despite prior conventional or biologic treatment options.”

U-XCEL included the same primary key secondary endpoints as U-EXCEED, with clinical remission measured by the Crohn’s Disease Activity Index (CDAI) and patient reported symptoms of stool frequency/abdominal pain (SF/AP).

The results showed that a greater proportion of individuals treated with a 12-week induction regimen of upadacitinib daily achieved clinical remission at 49% compared with the placebo at 29%, according to CDAI scores.

Similar results were seen with clinical remission with SF/AP at 51% and 22%, respectively.

Additionally, a greater proportion of individuals treated with upadacitinib achieved endoscopic response at 46% compared with the placebo group at 13% at week 12.

These results were consistent with results from the U-EXCEED induction study, which showed that individuals receiving upadacitinib achieved steroid-free clinical remission per CDAI and SF/AP compared with the placebo at week 12, among individuals taking corticosteroids at baseline.

During U-EXCEED, early symptom improvements at week 2, as well as clinical remission at week 4, were also achieved by a higher proportion of those receiving upadacitinib.

During the 12-week period, the safety profile of upadacitinib was consistent with the safety profile already observed with the drug across previous indications, and no new safety risks were observed.

The most common adverse events (AEs) were acne and anemia in the upadacitinib group. Additionally, serious AEs occurred in 6.9% of individuals compared with 6.8% in the placebo group.

Serious infection rates were 1.1% for those individuals in the upadacitinib group and 1.7% for those receiving the placebo.

Furthermore, herpes zoster was reported in 2.9% of individuals treated with upadacitinib, but all cases were not serious.

There were no cases of adjudicated death or gastrointestinal (GI) perforation during the placebo-controlled study period, and there was just 1 case of adjudicated major cardiovascular event reported in the placebo group.

Individuals who did not achieve clinical response at week 12 were included in an additional 12-week study with upadacitinib at the 30-mg strength. In this study, 1 individual died of COVID-19, and individuals who took the placebo and did not achieve a clinical response at week 12 were included in a 12-week treatment study of upadacitinib at the 45-mg strength.

Among these individuals, there was just 1 case of adjudicated GI perforation.

Reference

Second phase 3 induction study confirms upadacitinib (Rinvoq) improved clinical and endoscopic outcomes in patients with Crohn's disease. AbbVie. News release. February 24, 2022. Accessed February 25, 2022. https://news.abbvie.com/news/press-releases/second-phase-3-induction-study-confirms-upadacitinib-rinvoq-improved-clinical-and-endoscopic-outcomes-in-patients-with-crohns-disease.htm