Clin Gastroenterol Hepatol. 2022 Mar;20(3):578-590.e4.doi: 10.1016/j.cgh.2021.02.025. Epub 2021 Feb 19.

William J Sandborn ¹, Rory Rebuck ², Yuhua Wang ², Bin Zou ², Omoniyi J Adedokun ², Christopher Gasink ³, Bruce E Sands ⁴, Stephen B Hanauer ⁵, Stephan Targan ⁶, Subrata Ghosh ⁷, Willem J S de Villiers ⁸, Jean-Frederic Colombel ⁴, Brian G Feagan ⁹, John P Lynch ²

Author information

¹Division of Gastroenterology, Clinical Operations, Department of Medicine, University of California San Diego Inflammatory Bowel Disease Center, University of California San Diego, La Jolla, California. Electronic address: wsandborn@ucsd.edu.

²Immunology, Janssen Research & Development, LLC, Spring House, Pennsylvania.

³Medical Affairs, Janssen Scientific Affairs, LLC, Horsham, Pennsylvania.

⁴Feinstein IBD Clinical Center, Icahn School of Medicine at Mount Sinai, New York, New York.

⁵Digestive Health Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

⁶F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.

⁷School of Medicine and Health, University College Cork, Ireland and Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom.

⁸University of Stellenbosch, Stellenbosch, South Africa.

⁹Robarts Clinical Trials, Robarts Research Institute, London, Canada.

Abstract

Background & aims: The IM-UNITI study and long-term extension (LTE) evaluated the long-term efficacy, safety, and immunogenicity of subcutaneous ustekinumab maintenance therapy in patients with Crohn's disease. Here, we report the final results of IM-UNITI LTE through 5 years.

Methods: Patients completing safety and efficacy evaluations at week 44 of the maintenance study were eligible to participate in the LTE and continue the treatment they were receiving. Unblinding occurred after completion of maintenance study analyses (August 2015), and patients receiving placebo were discontinued from the study after unblinding. No dose adjustment occurred in the LTE. Efficacy assessments were conducted every 12 weeks until unblinding and at dosing visits thereafter through week 252. Serum ustekinumab concentrations and antidrug antibodies were evaluated through weeks 252 and 272, respectively.

Results: Using an intent-to-treat analysis of all patients randomized to ustekinumab at maintenance baseline, 34.4% of patients in the every-8-weeks group and 28.7% in the every-12-weeks group were in clinical remission at week 252. Corresponding remission rates among patients who entered the LTE were 54.9% and 45.2%. Overall, adverse event rates (per 100 patient-years) from maintenance week 0 through the final visit generally were similar in the placebo and combined ustekinumab groups for all adverse events (440.3 vs 327.6), serious adverse events (19.3 vs 17.5), infections (99.8 vs 93.8), and serious infections (3.9 vs 3.4). Serum ustekinumab concentrations were maintained throughout the LTE. Antidrug antibodies occurred in 5.8% of patients who received ustekinumab during induction and maintenance and continued in the LTE.

Conclusions: Patients receiving subcutaneous ustekinumab maintained clinical remission through 5 years. No new safety signals were observed. ClinicalTrials.gov number NCT01369355.