Upadacitinib Safe, Efficacious Maintenance Therapy for Active Crohn Disease

Upadacitinib is a safe and efficacious treatment for moderate to severe active Crohn disease.

Among patients with moderate to severe active Crohn disease (CD) who responded to upadacitinib induction therapy, upadacitinib maintenance therapy was superior to placebo and well-tolerated, according to study results presented at the Advances in Inflammatory Bowel Diseases (AIBD) 2022 conference, held from December 5 to 7, 2022, in Orlando, Florida.

The U-ENDURE study was a phase 3 clinical trial that enrolled patients with moderate to severe active CD. The patients (N=505) who responded to 12 weeks of 45 mg daily upadacitinib, in which response was defined as at least a 30% decrease in daily soft/liquid stool frequency (SF) and/or average daily abdominal pain score (APS), were eligible to proceed to the maintenance stage of the study. For maintenance therapy, patients were randomly assigned 1:1:1 to receive 15 mg upadacitinib (n=169), 30 mg upadacitinib (n=168), or placebo (n=168) daily for 52 weeks. The primary endpoints were endoscopic response and clinical remission, assessed using the Crohn disease activity index (CDAI) or SF and APS.

At week 52, CDAI clinical remission was achieved by 37.3%, 47.6%, and 15.1%; SF/APS clinical remission was achieved by 35.5%, 46.4%, and 14.4%; and endoscopic response was achieved by 27.6%, 40.1%, and 7.3% for the low-dose upadacitinib, high-dose upadacitinib, and placebo groups, respectively. All 3 endpoints were achieved by significantly more upadacitinib recipients compared with placebo (all P <.0001).

[Upadacitinib 15 mg] and [upadacitinib 30 mg] maintenance treatments were well tolerated and superior to [placebo] for all clinical and endoscopic outcomes, and most quality-of-life outcomes at [week] 52.

Similarly, both doses of upadacitinib were favored over placebo for the secondary endpoints of clinical response (41.4%-51.2% vs 15.2%; P <.01), endoscopic remission (19.1%-28.6% vs 5.5%; P <.01), maintenance of CDAI remission (49.5%-65.2% vs 21.2%; P <.01), maintenance of SF/APS remission (50.5%-60.0% vs 19.6%; P <.01), corticoid-free CDAI clinical remission (36.7%-46.4% vs 14.5%; P <.01), and corticoid-free SF/APS clinical remission (34.9%-44.6% vs 14.4%; P <.01), respectively.

Among the subset of patients with steroid use at baseline, both upadacitinib doses were favored over placebo for corticoid-free clinical remission, clinical and endoscopic remission, and change from baseline in Inflammatory Bowel Disease Questionnaire total scores (all P<.01).

The most common adverse event was CD worsening, occurring at a rate of 29.7 per 100 person-years (py) for 15 mg upadacitinib, 12.0 per 100 py for 30 mg upadacitinib, and 58.0 per 100 py for placebo. The rate of herpes zoster was higher among high-dose upadacitinib recipients (7.2 per 100 py) compared with placebo (4.7 per 100 py) or low-dose upadacitinib (4.0 per 100 py).

“Among patients with moderate to severe active CD who respond to UPA [upadacitinib] induction therapy, UPA15 [upadacitinib 15 mg] and UPA30 [upadacitinib 30 mg] maintenance treatments were well tolerated and superior to PBO [placebo] for all clinical and endoscopic outcomes, and most quality-of-life outcomes at [week] 52,” the study authors wrote.

Disclosure: One study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures.

References:

Panes J, Loftus Jr E, Lacerda A, et al. Efficacy and safety of upadacitinib maintenance therapy in patients with moderately to severely active Crohn’s disease: U-ENDURE phase 3 results. Abstract presented at: AIBD 2022; December 5-7, 2022; Orlando, FL. Abstract 37.