Clin Gastroenterol Hepatol. 2024 Jan;22(1):144-153.e2.doi: 10.1016/j.cgh.2023.06.014. Epub 2023 Jun 28.

Jean-Frédéric Colombel ¹, Bruce E Sands ², Christopher Gasink ³, Benjamin Yeager ⁴, Omoniyi J Adedokun ⁵, James Izanec ⁶, Tony Ma ⁶, Long-Long Gao ⁶, Scott D Lee ⁷, Stephan R Targan ⁸, Subrata Ghosh ⁹, Stephen B Hanauer ¹⁰, William J Sandborn ¹¹

Author information

¹Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: jean-frederic.colombel@mssm.edu.

²Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.

³Janssen Scientific Affairs, LLC, Horsham, Pennsylvania; Intercept Pharmaceuticals, Morristown, New Jersey.

⁴Temple University Health System, Philadelphia, Pennsylvania.

⁵Janssen Research & Development, LLC, Spring House, Pennsylvania.

⁶Janssen Scientific Affairs, LLC, Horsham, Pennsylvania.

⁷University of Washington Medical Center, Seattle, Washington.

⁸Cedars-Sinai Medical Center, Los Angeles, California.

⁹IAPC Microbiome Ireland, College of Medicine and Health, University College Cork, Ireland.

¹⁰Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

¹¹University of California San Diego, La Jolla, California; Ventyx Biosciences, Inc., Encinitas, California.

Abstract

Background & aims: Ustekinumab is an effective treatment of Crohn's disease (CD). Of interest to patients is knowing how soon symptoms may improve. We analyzed ustekinumab response dynamics from the ustekinumab CD trials.

Methods: Patients with CD received intravenous induction with ustekinumab ∼6 mg/kg (n = 458) or placebo (n = 457). Week 8 ustekinumab responders received subcutaneous ustekinumab 90 mg as the first maintenance dose or as an extended induction dose for nonresponders. Patient-reported symptom changes (stool frequency, abdominal pain, general well-being) within the first 14 days and clinical outcomes through week 44 were evaluated using the CD Activity Index.

Results: After ustekinumab infusion, stool frequency improvement was significantly (P < .05) greater than placebo on day 1 and for all patient-reported symptoms by day 10. In patients with no history of biologic failure or intolerance, cumulative clinical remission rates increased from 23.0% at week 3 to 55.5% at week 16 after the subcutaneous dose at week 8. Corresponding cumulative rates for patients with a history of biologic failure or intolerance increased from 12.9% to 24.1%. Neither change from baseline in CD Activity Index score nor week 8 ustekinumab pharmacokinetics were associated with week 16 response. Among all patients who received subcutaneous ustekinumab 90 mg q8w, up to 66.7% were in clinical response at week 44.

Conclusions: Ustekinumab induction provided symptom relief by day 1 post-infusion. Following ustekinumab infusion and a subcutaneous 90 mg injection, clinical outcomes continued to increase through week 16 and up to week 44. Regardless of week 8 clinical status or ustekinumab pharmacokinetics, patients should receive additional treatment at week 8.

Clinicaltrials: gov numbers, NCT01369329, NCT01369342, and NCT01369355.