Five-year Efficacy and Safety of Ustekinumab Treatment in Crohn's Disease: the IM-UNITI trial.

Background and 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 (CD). Here we report 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. 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 anti-drug antibodies (ADAs) 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 q8w group and 28.7% in the q12w 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 were generally 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. ADAs occurred in 5.8% of patients who received ustekinumab during induction and maintenance and continued in the LTE. Conclusion Patients receiving subcutaneous ustekinumab maintained clinical remission through 5 years. No new safety signals were observed. ClinicalTrials.gov number NCT01369355