Abstract and Introduction
Background: The ongoing UNIFI long-term extension evaluates subcutaneous ustekinumab for moderate-to-severe ulcerative colitis (UC) from weeks 44 through 220.
Aims: To assess efficacy (through week 92) and safety (through week 96) during the long-term extension
Methods: Overall, 399 responders to intravenous ustekinumab induction and who were randomised to maintenance therapy were treated in the long-term extension (115 received subcutaneous placebo, 141 received ustekinumab 90 mg every 12 weeks [q12w], and 143 received ustekinumab 90 mg q8w). Placebo treatment was discontinued at unblinding after week 44. Partial Mayo scores were collected every 12 weeks and at each dosing visit after unblinding. Safety was evaluated throughout.
Results: Among all patients randomised in maintenance, symptomatic remission rates (stool frequency = 0/1; rectal bleeding = 0) at week 92 were, 64.5% and 67.6% in the ustekinumab q12w and q8w groups, respectively. Among randomised patients treated in the long-term extension, 78.7% and 83.2% of patients receiving q12w and q8w, respectively, attained symptomatic remission at week 92; >95% of patients in symptomatic remission at week 92 were corticosteroid-free. Both ustekinumab groups maintained efficacy through week 92. From weeks 44 to 96, adverse events (AEs) per hundred patient-years (PY) of follow-up for combined ustekinumab vs placebo were: 255.68 vs 267.93; serious AEs, 9.34 vs 12.69; malignancies (including non-melanoma skin cancers), 0.93 vs 1.49; and serious infections, 2.33 vs 2.99. One patient with multiple comorbidities who received one ustekinumab dose after dose adjusting from placebo experienced a fatal cardiac arrest.
Conclusions: The efficacy of ustekinumab in patients with UC was sustained through 92 weeks. No new safety signals were observed (ClinicalTrials.gov number, NCT02407236).
Ulcerative colitis (UC) is a chronic progressive idiopathic inflammatory disease of the large bowel that is characterised by symptoms of bloody diarrhoea, faecal urgency, abdominal cramps, and mucosal inflammation. Patients with UC typically require long-term therapy to control symptoms.
Ustekinumab is an interleukin-12/23p40 antagonist that is approved for Crohn's disease and more recently for UC. In the "Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Subjects with Moderately to Severely Active UC" study we call UNIFI (NCT02407236), ustekinumab was demonstrated to induce and maintain clinical remission and clinical response through 52 weeks of treatment in patients who had failed conventional or biologic therapy (tumour necrosis factor-α [TNF-α] antagonists and/or an α4β7 integrin mucosal addressin cell adhesion molecule-1 [MAdCAM-1] antagonist, vedolizumab) or who were biologic therapy naive. Here we describe the maintenance of efficacy (Week 92) and safety (Week 96) through the first year of the UNIFI long-term extension.
Aliment Pharmacol Ther. 2020;52(11-12):1658-1675. © 2020 Blackwell Publishing