P2203 - Association Between Efficacy and Long-Term Outcomes: Four Year Results From the UNIFI Study of Ustekinumab in Ulcerative Colitis

Monday, October 23, 2023

10:30 AM – 4:15 PM PT

Location: Exhibit Hall

Has Audio

Presenting Author(s)

Bruce E. Sands, MD, MS, FACG

Icahn School of Medicine at Mount Sinai
New York, New York

Laurent Peyrin-Biroulet, MD, PhD¹, Rupert Leong, MD², Bruce E. Sands, MD, MS, FACG³, Ye Miao, MS⁴, Colleen Marano, MD⁴, Silvio Danese, MD, PhD⁵
¹Last Inserm U954 and CHU de Nancy, Lorraine University, Vandoeuvre-lès-Nancy, Lorraine, France; ²Macquarie University Hospital Clinic, Sydney, New South Wales, Australia; ³Icahn School of Medicine at Mount Sinai, New York, NY; ⁴Janssen Research & Development, LLC, Spring House, PA; ⁵IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Lombardia, Italy

Introduction: Long-term outcomes from the UNIFI study of ulcerative colitis (UC) are presented for patients who achieved symptomatic remission after induction with intravenous (IV) ustekinumab (UST) with or without histo-endoscopic mucosal improvement (HEMI).

Methods: In UNIFI, patients were randomised to IV UST (130 mg or ~6 mg/kg/body weight) or placebo (PBO). Patients who were in clinical response 8 weeks (w) following IV induction with UST were randomized to subcutaneous (SC) UST 90 mg every 12 weeks (q12w) or q8w or SC PBO maintenance. At the discretion of the investigator, enrolment in this long-term extension study was optional for patients who completed 44w of maintenance. Outcomes included HEMI (having both histologic improvement [< 5% neutrophils in the epithelium, no crypt destruction, and no erosions, ulcerations, or granulations] and endoscopic improvement [Mayo endoscopic subscore 0 or 1]) and symptomatic remission (a stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0). Patients were stratified by efficacy 8w after IV induction as: 1) disease clearance (achieving both HEMI and symptomatic remission [n=79]), 2) symptomatic remission without HEMI (n=142), or 3) neither symptomatic remission nor HEMI (n=82). Time to treatment failure (UC-related surgery or hospitalization, adverse event of UC, or discontinuation of study agent due to an adverse event of worsening UC or lack of efficacy) was compared between cohorts by using a log-rank test.

Results: Proportions of patients in symptomatic remission were highest for those who were in disease clearance after induction through 200w (~4 years) of UST treatment (Table). The time to treatment failure was longer in patients with disease clearance than patients in symptomatic remission without HEMI (p=0.004), and in patients in symptomatic remission without HEMI than patients with neither symptomatic remission nor HEMI (p=0.043) (Figure).

Discussion: Patients with disease clearance 8w after IV induction had greater long-term symptomatic remission outcomes and longer time to treatment failure than those with symptomatic remission without HEMI or those with neither symptomatic remission nor HEMI after induction.

Figure: Kaplan-Meier curve for time to treatment failure (UC-related surgery or hospitalization, adverse event of UC, or discontinuation of study agent because of lack of efficacy or adverse event of worsening UC) in patients receiving SC maintenance ustekinumab

Disclosures:

Laurent Peyrin-Biroulet: AbbVie – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Allergan – personal fees. Alma – personal fees. Amgen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Applied Molecular Transport – personal fees. Arena – personal fees. Biogaran – Advisory Committee/Board Member, Consultant, Speakers Bureau. Biogen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant, Speakers Bureau. Bristol Myers Squibb – personal fees. Celgene – Advisory Committee/Board Member, Consultant, Speakers Bureau. Celltrion – Advisory Committee/Board Member, Consultant, Speakers Bureau. CTMA – Stock Options. Eli Lilly – Advisory Committee/Board Member, Consultant, Speakers Bureau. Enterome – personal fees. Enthera – personal fees. Ferring – Advisory Committee/Board Member, Consultant, Speakers Bureau. Forward Pharma – Advisory Committee/Board Member, Consultant, Speakers Bureau. Fresenius – personal fees. Genentech – Advisory Committee/Board Member, Consultant, Speakers Bureau. Gilead – personal fees. H.A.C. Pharma – Advisory Committee/Board Member, Consultant, Speakers Bureau. Hikma – personal fees. Hospira/Pfizer – Advisory Committee/Board Member, Consultant, Speakers Bureau. Index Pharmaceuticals – Advisory Committee/Board Member, Consultant, Speakers Bureau. Janssen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Lycera – Advisory Committee/Board Member, Consultant, Speakers Bureau. Merck – Advisory Committee/Board Member, Consultant, Speakers Bureau. Mitsubishi – Advisory Committee/Board Member, Consultant, Speakers Bureau. MSD – Grant/Research Support, personal fees. Mylan – personal fees. Nestlé – personal fees. Norgine – Advisory Committee/Board Member, Consultant, Speakers Bureau. Oppilan Pharma – personal fees. OSE Immunotherapeutics – personal fees. Pfizer – personal fees. Pharmacosmos – personal fees. Roche – personal fees. Samsung Bioepis – Advisory Committee/Board Member, Consultant, Speakers Bureau. Sandoz – Advisory Committee/Board Member, Consultant, Speakers Bureau. Sterna – personal fees. Sublimity Therapeutics – personal fees. Takeda – Advisory Committee/Board Member, Consultant, Speakers Bureau. Theravance – Advisory Committee/Board Member, Consultant, Speakers Bureau. Tillots – Advisory Committee/Board Member, Consultant, Speakers Bureau. Vifor – Advisory Committee/Board Member, Consultant, Speakers Bureau.

Rupert Leong: AbbVie – Consultant. Aspen – Consultant. Celgene – Consultant. Dr Falk Pharma – Consultant. Endochoice – Grant/Research Support. Ferring – Consultant, Grant/Research Support. GESA – Grant/Research Support. Hospira – Consultant. Janssen – Grant/Research Support. Janssen R&D, LLC – Consultant. MSD – Consultant. NHMRC – Grant/Research Support. Novartis – Consultant. Pfizer – Consultant. Shire – Grant/Research Support. Takeda – Consultant.

Bruce Sands: AbbVie – Consultant. Abivax – Consultant, Speaker’s fees. Adiso Therapeutics – Consultant. Alimentiv – Consultant. Amgen – Consultant. Arena pharmaceuticals – Consultant. Artizan Biosciences – Consultant. Artugen Therapeutics – Consultant. AstraZeneca – Consultant. Bacainn Therapeutics – Consultant. Biora Therapeutics – Consultant. Boehringer Ingelheim – Consultant. Boston Pharmaceuticals – Consultant. Bristol Myers Squibb – Consultant, Grant/Research Support, speaking fees and other support. Calibr – Consultant. Celltrion – Consultant. ClostraBio – Consultant. Connect Biopharm – Consultant. Cytoki Pharma – Consultant. Eli Lilly – Consultant, speaking fees and other support. Enthera – Consultant. Evommune – Consultant. Ferring – Consultant. Fresenius Kabi – Consultant. Galapagos – Consultant. Genentech – Consultant. Gilead Sciences – Consultant. GlaxoSmithKline – Consultant. Gossamer Bio – Consultant. HMP Acquisition – Consultant. Imhotex – Consultant. Immunic – Consultant. InDex Pharmaceuticals – Consultant. Innovation Therapeutics – Consultant. Inotrem – Consultant. Ironwood Pharmaceuticals – Consultant. Janssen – Grant/Research Support, consulting and speaking fees and other support. Johnson & Johnson – Consultant. Kaleido Biosciences – Consultant. Kallyope – Consultant. Merck – Consultant. MiroBio – Consultant. Morphic Therapeutics – Consultant. MRM Health – Consultant. OSE Immunotherapeutics – Consultant. Pfizer Inc – Consultant, Grant/Research Support, speaking fees and other support. Progenity – Consultant. Prometheus Biosciences – Consultant. Prometheus Laboratories – Consultant. Protagonist Therapeutics – Consultant. Q32 Bio – Consultant. RedHill Biopharma – Consultant. Sun Pharma – Consultant. Surrozen – Consultant. Synlogic Operating Company – Consultant. Takeda – Grant/Research Support, consulting and speaking fees and other support. Target RWE – Consultant. Theravance Biopharma – Consultant, Grant/Research Support. TLL Pharmaceutical – Consultant. USWM Enterprises – Consultant. Ventyx Biosciences – Consultant, personal fees and stock options for consulting. Viela Bio – Consultant.

Ye Miao: Johnson & Johnson – Employee, Stock Options, Stock-publicly held company(excluding mutual/index funds).

Colleen Marano: Janssen R&D, LLC – Employee.

Silvio Danese: AbbVie – Consultant, personal fees (lecture fees). Alimentiv – Consultant. Allergan – Consultant, personal fees. Amgen – Consultant, lecture fees. Applied Molecular Transport – Consultant. AstraZeneca – Consultant, personal fees. Athos Therapeutics – Consultant, personal fees. Biogen – Consultant, personal fees. Boehringer Ingelheim – Consultant, personal fees. Bristol Myers Squibb – Consultant. Celgene – Consultant, personal fees. Celltrion Healthcare – Consultant, Personal fees. Dr Falk Pharma – Consultant. Eli Lilly – Consultant, personal fees. Enthera – Consultant, personal fees. Ferring Pharmaceuticals – Consultant, lecture fees. Gilead – Consultant, lecture fees. Hospira – Consultant, personal fees. Inotrem – Consultant, personal fees. Janssen Pharmaceuticals – Consultant, lecture fees. Johnson & Johnson – Consultant, personal fees. Morphic – Consultant. MSD – Consultant, personal fees. Mundipharma – Consultant, personal fees. Mylan – Consultant, lecture fees. Pfizer – Consultant, lecture fees. Roche – Consultant, personal fees. Sandoz – Consultant, personal fees. Sublimity Therapeutics – Consultant, personal fees. Takeda – Consultant, lecture fees. Teladoc Health – Consultant. TiGenix – Consultant, personal fees. UCB – Consultant, personal fees. Vial – Consultant. Vifor – Consultant, personal fees.

Laurent Peyrin-Biroulet, MD, PhD¹, Rupert Leong, MD², Bruce E. Sands, MD, MS, FACG³, Ye Miao, MS⁴, Colleen Marano, MD⁴, Silvio Danese, MD, PhD⁵. P2203 - Association Between Efficacy and Long-Term Outcomes: Four Year Results From the UNIFI Study of Ustekinumab in Ulcerative Colitis, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.