Upadacitinib Achieved Primary Endpoints in Crohn’s Disease Study

The results of AbbVie’s U-EXCEED study indicated that a significantly higher percentage of patients with Crohn’s disease receiving upadacitinib 45 mg once daily were able to achieve both clinical remission and endoscopic response at Week 12.

Crohn’s disease, a systemic, progressive, unpredictable disease, inflames the gastrointestinal tract and causes consistent abdominal pain and diarrhea. Upadacitinib, a reversible Janus kinase (JAK) inhibitor, may be able to help patients achieve clinical remission.

U-EXCEED is a phase 3, multicenter, randomized, double-blind, placebo-controlled study analyzing the safety and efficacy of upadacitinib 45 mg. It was sectioned into 3 parts, the first which is a 12-week placebo-controlled induction study (NCT03345836). In Part 2, the open-label arm, a supplementary group was added for 12 weeks. Participants who did not achieve clinical response in either Part 1 or Part 2 were initiated into Part 3, in which patients received upadacitinib 45 mg or 30 mg for an additional 12 weeks.

Eligible patients were aged between 18 and 75 years, had confirmed moderate-to-severe Crohn’s disease with an inadequate response or intolerance to biologic therapy, and were diagnosed with Crohn’s disease for a minimum of 3 months at baseline. Over 60% of patients evaluated had previously failed at least 2 biologics. ‘

Clinical remission was determined by the Crohn’s Disease Activity Index (CDAI), as defined as CDAI <150, per the US Food and Drug Administration (FDA). Patient-reported stool frequency and/or abdominal pain (SF/AP), per the EU European Medicines Agency (EU EMA), was defined as average daily very soft or liquid stool frequency ≤2.8 coupled with an average daily abdominal pain score ≤1.0. Both scores could not be greater than baseline. Investigators also examined improvement in intestinal mucosa via endoscopy, which was defined as decrease in simple endoscopic score for Crohn’s disease (SES-CD) of >50% from baseline.

At Week 12, a significantly larger proportion of patients treated with upadacitinib 45 mg daily achieved steroid-free clinical remission when compared with placebo (39% vs 21%, respectively; p<0.0001). Additionally, patients in the upadacitinib cohort saw more clinical remission in terms of SF/AB when compared with the placebo group (40% vs 14%, respectively; p<0.0001). A significantly higher percentage of patients were able to attain endoscopic response when compared with placebo (35% vs 4%, respectively; p<0.0001). Early symptom improvement, defined as a reduction of CDAI ≥100 points from baseline, was observed at Week 2 as well as clinical remission at Week 4.

The safety profile was consistent with previous findings and there were no new safety risks observed. The most common adverse reaction was nasopharyngitis. Serious adverse events were similar in both upadacitinib and placebo groups, (9.9% vs 9.3%, respectively). Serious infections were seen in 2.8% of patients in the upadacitinib group and 1.8% in the placebo group.

"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," stated vice chairman and president of AbbVie, Michael Severino, MD. "We continue to leverage our expertise in [inflammatory bowel disease] (IBD) by driving research and development that help shape the IBD landscape and elevate standards of care for patients."