Upadacitinib Phase 2b Data Demonstrates Remission Induction for Ulcerative Colitis

Positive phase 2b data from AbbVie’s upadacitinib, an investigational JAK1-selective inhibitor for the induction and maintenance therapy in adult patients with moderately to severely active ulcerative colitis, have been released.

Aside from meeting the primary endpoint of clinical remission, highlights included met secondary endpoints, endoscopic improvement, and clinical response in patients.

"While treatment of ulcerative colitis has come a long way, patients are still in need of therapies like upadacitinib that have the potential to provide disease control," Marek Honczarenko, MD, PhD, vice president, global immunology development, AbbVie, said in a recent statement. "These results support the initiation of the phase 3 clinical trial program to further evaluate upadacitinib in ulcerative colitis.”

Results from the phase 2b trial are part of U-ACHIEVE, an ongoing phase 2b/3 multicenter, randomized, double-blind, placebo-controlled clinical trial evaluating patients with moderately to severely active ulcerative colitis.

The objective of the phase 2b trial was to characterize the dose-response, efficacy, and safety of upadacitinib compared to placebo in inducing clinical remission. This data was necessary in order to identify the induction dose of upadacitinib for further study in phase 3 studies.

Enrollment criteria for patients in the trial included inadequate response, loss of response or intolerance to corticosteroids, and immunosuppressants or biologic therapies.

Patients were randomized and administered induction therapy with placebo or upadacitinib 7.5, 15, 30 or 45 mg once daily for 8 weeks.

Patients who achieved clinical remission, which was defined as stool frequency subscore [SFS] ≤1, rectal bleeding subscore [RBS] of 0, and endoscopic subscore [ES] ≤1 at week 8 served as the primary endpoint.

Endoscopic improvement (ES ≤1), clinical remission (per Full Mayo score ≤2 with no subscore >1) and clinical response (decrease from baseline in the Adapted Mayo score >2 points and >30% from baseline in the Adapted Mayo Score, plus a decrease in RBS >1 or an absolute RBS <1) at week 8 served as secondary endpoints.

Among the results, investigators observed achievement of clinical remission (per Adapted Mayo score) in significantly more patients at week 8 with upadacitinib (14/14/20%of patients in the 15/30/45 mg groups) compared to placebo (0%). Achievement of key secondary endpoints—endoscopic improvement, clinical remission (per Full Mayo Score) and clinical response (per Adapted Mayo Score)&mdash;at week 8 across the upadacitinib 15/30/45 mg groups was also observed.

However, investigators noted the primary endpoint was not met in the upadacitinib 7.5 mg group.

"The U-ACHIEVE study included patients with difficult-to-treat ulcerative colitis, the majority of whom had failed multiple previous therapies, including biologics,” William Sandborn, MD, lead study investigator and director, Inflammatory Bowel Disease Center chief, Division of Gastroenterology and Professor of Medicine at the University of California, San Diego, shared. “These results further extend our understanding of upadacitinib's potential as an important treatment option for ulcerative colitis patients."

Data from patient-reported outcomes regarding upadacitinib treatment were also collected. In 1 analysis, patients reported greater improvements in ulcerative colitis symptoms, such as bowel urgency, abdominal pain, rectal bleeding, and stool frequency, with upadacitinib treatment compared to placebo.

Another analysis reported significant and clinically meaningful improvements in disease-specific and general health-related quality of life, fatigue, work productivity, and the ability to perform daily activities in more patients treated with upadacitinib after 8 weeks of treatment compared to placebo.

Regarding future action, phase 3 trials evaluating upadacitinib in ulcerative colitis have been initiated.

Upadacitinib is also being studied in multiple immune-mediated diseases.