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Clinical Trial
. 2025 Sep;62(5):483-492.
doi: 10.1111/apt.70264. Epub 2025 Jul 16.

Clinical Trial: Association Between Early Disease Clearance and Long-Term Outcomes-4-Year Results From the Phase 3 UNIFI Study of Ustekinumab in Ulcerative Colitis

Silvio Danese  1 , Rupert W Leong  2   3 , Bruce E Sands  4 , Tony Ma  5 , Colleen Marano  6 , Laurent Peyrin-Biroulet  7   8
Affiliations
Clinical Trial

Clinical Trial: Association Between Early Disease Clearance and Long-Term Outcomes-4-Year Results From the Phase 3 UNIFI Study of Ustekinumab in Ulcerative Colitis

Silvio Danese et al. Aliment Pharmacol Ther. 2025 Sep.

Abstract

Background: Achievement of disease clearance (simultaneous symptomatic remission and histo-endoscopic mucosal improvement [HEMI]) following induction therapy may lead to better long-term outcomes in ulcerative colitis (UC).

Aim: To evaluate disease clearance in the phase 3 UNIFI program and its association with long-term outcomes.

Methods: UNIFI comprised randomised, placebo-controlled induction and maintenance studies and a long-term extension, which evaluated intravenous ustekinumab induction (130 mg or ~6 mg/kg) and subcutaneous ustekinumab maintenance therapy (90 mg every 8 or 12 weeks) through 4 years in patients with UC.

Results: Disease clearance was achieved by 5.9%, 15.2% and 15.1% of patients 8 weeks after placebo or ustekinumab 130 mg or ~6 mg/kg induction, respectively. Among ustekinumab induction responders randomised to ustekinumab maintenance therapy who did or did not achieve disease clearance 8 weeks after induction, 63.6% and 35.2% (nominal p < 0.001), respectively, achieved clinical remission (Mayo score ≤ 2, no individual subscore > 1) at Week 44. Among ustekinumab induction responders randomised to ustekinumab maintenance therapy who achieved disease clearance, symptomatic remission without HEMI, or neither symptomatic remission nor HEMI 8 weeks after induction, 73.4%, 53.5% (nominal p = 0.002) and 45.1% (nominal p < 0.001), respectively, achieved symptomatic remission (Mayo stool frequency subscore 0/1, rectal bleeding subscore 0) and 58.2%, 46.5% (nominal p = 0.09) and 42.7% (nominal p = 0.05), respectively, achieved Inflammatory Bowel Disease Questionnaire remission (score ≥ 170) at Week 200.

Conclusions: Patients who achieved disease clearance 8 weeks after ustekinumab induction were more likely to be in long-term clinical, symptomatic and quality of life remission with ustekinumab maintenance treatment than patients who did not.

Trial registration: NCT02407236.

Keywords: disease clearance; ulcerative colitis; ustekinumab.

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Conflict of interest statement

Silvio Danese reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring, Gilead, Hospira, Inotrem, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity, Takeda, TiGenix, UCB, and Vifor; and reports lecture fees from AbbVie, Amgen, Ferring, Gilead, Johnson & Johnson, Mylan, Pfizer, and Takeda. Rupert W. Leong reports advisory board fees from AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Johnson & Johnson, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, and Takeda and research grants from Celltrion, Shire, Johnson & Johnson, Takeda, Joanna Tiddy grant from University of Sydney, McCusker Charitable Trust, Gastroenterological Society of Australia, NHMRC, Gutsy Group, and Pfizer. Bruce E. Sands reports non‐financial support from Johnson & Johnson during the conduct of the study and personal fees from Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Biolojic Design, Biora Therapeutics, Boehringer Ingelheim, Ensho Therapeutics, Enthera, Enveda Biosciences, Equilium, Evommune, Ferring, Fzata, Galapagos, Genetech, Gilead Sciences, GlaxoSmithKline, GossamerBio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Kaleido, Kallyope, Microba, Microbiotica, Mitsubishi Tanabe Pharma, Mobius Care, Morphic Therapeutics, MRM Health, Nexus Therapeutics, Immunyx Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Palisade Bio, Progenity, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Therapeutics, Reistone Biotherapeutics, Sorriso Pharmaceuticals, Spyre Therapeutics, Surrozen, Target RWE, Teva, Theravance Biopharma, TLL Pharmaceutical, TR1X, and Union Therapeutics; personal fees and non‐financial support from AbbVie, Abivax, AstraZeneca, Celltrion, Johnson & Johnson, Lilly, Merck, Pfizer, Prometheus Biosciences, and Takeda; and grants, personal fees, and non‐financial support from Bristol Myers Squibb and Johnson & Johnson; and stock, stock options, personal fees, and non‐financial support from Ventyx Biosciences, all outside of the submitted work. Tony Ma and Colleen Marano report employment with Johnson & Johnson, and Colleen Marano reports Johnson & Johnson stock ownership. Laurent Peyrin‐Biroulet reports grants or contracts from Celltrion, Fresenius Kabi, Medac, MSD, and Takeda; consulting for AbbVie, Abivax, Adacyte, Alfasigma, Alimentiv, Amgen, Applied Molecular Transport, Arena, Banook, Biogen, Bristol Myers Squibb, Celltrion, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, GlaxoSmithKline, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Iterative Health, Johnson & Johnson, LifeMine, Lilly, Medac, Mopac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign, Precision Medicine, ONO Pharma, OSE Immunotherapeutics, Par' Immune, Pfizer, Prometheus, Roche, Roivant, Samsung, Sandoz, Sanofi, Sorriso, Spyre, Takeda, Teva, ThirtyfiveBio, Tillots, Vectivbio, Vedanta, and Ventyx; lecture fees from AbbVie, Alfasigma, Amgen, Arena, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Iterative Health, Johnson & Johnson, Lilly, Medac MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, and Tillots; and travel support from Abbvie, Alfasigma, Amgen, Arena, Celltrion, Ferring, Galapagos, Genentech, Gilead, Johnson & Johnson, Lilly, Medac, Morphic, MSD, Pfizer, Sandoz, and Takeda.

Figures

FIGURE 1
FIGURE 1
Study design. *Patients who were receiving placebo SC at the time of study unblinding, which occurred after completion of the maintenance study analysis, were discontinued. IV, intravenous; PBO, placebo; q12w, every 12 weeks; q8w, every 8 weeks; SC, subcutaneous; UST, ustekinumab.
FIGURE 2
FIGURE 2
Achievement of disease clearance 8 weeks after IV ustekinumab induction (A) or at maintenance Week 44 among evaluable IV ustekinumab induction responders randomised to maintenance treatment (B). All p‐values are nominal and are versus placebo. IV, intravenous; q12w, every 12 weeks; q8w, every 8 weeks; SC, subcutaneous.
FIGURE 3
FIGURE 3
Achievement of outcomes at maintenance Week 44 by achievement of disease clearance following induction. All p‐values are nominal. HEMI, histo‐endoscopic mucosal improvement.
FIGURE 4
FIGURE 4
Achievement of symptomatic remission (A) or corticosteroid‐free symptomatic remission (B) through maintenance Week 200 by induction efficacy category. All p‐values are nominal and are versus disease clearance. HEMI, histo‐endoscopic mucosal improvement.
FIGURE 5
FIGURE 5
Time‐to‐treatment failure event through maintenance Week 220 by induction efficacy categories. Events of interest were defined as UC‐related surgery or hospitalisation, AE of UC, or discontinuation of study agent due to an AE of worsening UC or lack of efficacy. All p‐values are nominal. AE, adverse event; HEMI, histo‐endoscopic mucosal improvement; UC, ulcerative colitis.
FIGURE 6
FIGURE 6
Achievement of IBDQ remission (total score ≥ 170) through maintenance Week 200 by induction efficacy categories. All p‐values are nominal and are versus disease clearance. HEMI, histo‐endoscopic mucosal improvement; IBDQ, Inflammatory Bowel Disease Questionnaire.
See this image and copyright information in PMC

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