The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium.

Abstract

INTRODUCTION:

We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD).

METHODS:

This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation.

RESULTS:

A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients.

DISCUSSION:

UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

• Authors: Amanda M Johnson, Maria Barsky, Waseem Ahmed, Samantha Zullow, Jonathan Galati, Vipul Jairath, Neeraj Narula, Farhad Peerani, Benjamin H Click, Elliot S Coburn, ThucNhi Tran Dang, Stephanie Gold, Manasi Agrawal, Rajat Garg, Manik Aggarwal, Danah Mohammad, Brendan Halloran, Gursimran S Kochhar, Hannah Todorowski, Nabeeha Mohy Ud Din, James Izanec, Amanda Teeple, Chris Gasink, Erik Muser, Zhijie Ding, Arun Swaminath, Komal Lakhani, Dan Hogan, Samit Datta, Ryan C Ungaro, Brigid S Boland, Matthew Bohm, Monika Fischer, Sashidhar Sagi, Anita Afzali, Thomas Ullman, Garrett Lawlor, Daniel C Baumgart, Shannon Chang, David Hudesman, Dana Lukin, Ellen J Scherl, Jean-Frederic Colombel, Bruce E Sands, Corey A Siegel, Miguel Regueiro, William J Sandborn, David Bruining, Sunanda Kane, Edward V Loftus Jr, Parambir S Dulai
• Journal: The American journal of gastroenterology (Am J Gastroenterol) Vol. 118 Issue 2 Pg. 317-328 (02 01 2023) ISSN: 1572-0241 [Electronic] United States
• PMID: 36191274 (Publication Type: Multicenter Study, Journal Article)
• Copyright: Copyright © 2022 by The American College of Gastroenterology.

Chemical References

• Ustekinumab
• Biological Products

Topics

• Female
• Humans
• Male
• Ustekinumab (adverse effects)
• Crohn Disease (drug therapy)
• Retrospective Studies
• Remission Induction
• Treatment Outcome
• Necrosis (drug therapy)
• Biological Products (therapeutic use)