The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium
Authors: Johnson Amanda M. , Barsky Maria , Ahmed Waseem , Zullow Samantha , Galati Jonathan , Jairath Vipul , Narula Neeraj , Peerani Farhad , Click Benjamin H. , Coburn Elliot S. , Dang ThucNhi Tran , Gold Stephanie , Agrawal Manasi , Garg Rajat , Aggarwal Manik , Mohammad Danah , Halloran Brendan , Kochhar Gursimran S. , Todorowski Hannah , Ud Din Nabeeha Mohy , Izanec James , Teeple Amanda , Gasink Chris , Muser Erik , Ding Zhijie , Swaminath Arun , Lakhani Komal , Hogan Dan , Datta Samit , Ungaro Ryan C. , Boland Brigid S. , Bohm Matthew , Fischer Monika , Sagi Sashidhar , Afzali Anita , Ullman Thomas , Lawlor Garrett , Baumgart Daniel C. , Chang Shannon , Hudesman David , Lukin Dana , Scherl Ellen J. , Colombel Jean-Frederic , Sands Bruce E. , Siegel Corey A. , Regueiro Miguel , Sandborn William J. , Bruining David , Kane Sunanda , Loftus Edward V. , Dulai Parambir S. 
Published: October 2022

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.