Upadacitinib Provides Rapid Relief in Crohn’s Disease

TOPLINE:

Upadacitinib improved soft/liquid stool frequency (SF) and abdominal pain scores (APS) within the first week of treatment in patients with moderate to severe Crohn’s disease, including those with prior biologic failure.

METHODOLOGY:

• Researchers conducted a post hoc analysis of pooled data from two phase 3 12-week induction trials — U-EXCEL and U-EXCEED — to evaluate symptom relief in patients with Crohn’s disease. U-EXCEL included patients with or without prior biologic failure; U-EXCEED included patients with prior biologic failure only.
• Overall, 1021 patients aged 18-75 years with a mean daily very soft or liquid SF of ≥ 4, APS of ≥ 2, a Simple Endoscopic Score for Crohn’s disease of ≥ 6, and with or without prior biologic failure received once-daily 45 mg upadacitinib (n = 674) or placebo (n = 347).
• Daily diary data were used to analyze any improvement in SF and APS for the first 15 days of starting treatment with upadacitinib or placebo.
• SF/APS clinical remission was defined as a daily SF of < 3 and a daily APS of ≤ 1.
• Patients who achieved SF/APS clinical response after 12 weeks were randomized to a maintenance trial — U-ENDURE — in which they received once-daily 15 mg upadacitinib, 30 mg upadacitinib, or placebo for 52 weeks.

TAKEAWAY:

• For the 12-week induction trials, a higher proportion of patients receiving upadacitinib vs patients given placebo achieved daily SF/APS clinical remission at day 5 (16.7% vs 9.2%; P ≤ .01), with further improvements in the upadacitinib group seen through day 15.
• The median time required to achieve daily SF/APS clinical remission was 13 days with upadacitinib vs 32 days with placebo (P < .0001).
• Upadacitinib led to more rapid symptom relief than placebo in the subgroup of patients with prior biologic failure than in those without prior biologic failure.
• In patients receiving upadacitinib, the SF/APS clinical remission rate also improved by week 2 to 21.1% compared to 8.9% in the placebo group and was maintained at all verified timepoints through week 12 (P < .0001).
• Through week 52 of the maintenance trial, most patients also maintained high rates of clinical outcomes with upadacitinib vs placebo.

IN PRACTICE:

“Patients with [Crohn’s disease] may benefit from a convenient therapy that provides quick improvement and early symptom resolution without the consequences of excessive or prolonged corticosteroid use,” the authors wrote.

SOURCE:

This study, led by Jean-Frédéric Colombel, MD, from the Department of Medicine, Icahn School of Medicine at Mount Sinai, New York City, was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

Limitations included a small proportion of patients without prior biologic failure as well as a small number of patients with 52-week assessments. In addition, the nominal P values included in this post hoc analysis were not multiplicity controlled. Given that 30% and 18% of patients had APS ≤ 1 and SF < 3 at baseline, researchers assessed daily APS/SF remission among patients with elevated baseline APS (≥ 2) and those with elevated baseline SF (≥ 4) and noted similarly rapid symptom improvement with upadacitinib compared to the data for the overall study population.

DISCLOSURES:

This study was funded by AbbVie. Six authors declared being employees of and owning stocks in AbbVie. The other authors declared having several ties with various sources, including AbbVie.