D0407 - Corticosteroid-Sparing Effects of Ustekinumab Therapy for Ulcerative Colitis Through 4 Years: UNIFI Long-Term Extension

Tuesday, October 25, 2022

10:00 AM – 12:00 PM ET

Location: Crown Ballroom

Has Audio

Presenting Author(s)

MA

Maria T. Abreu, MD

The University of Miami Health System
Miami, FL

Maria T. Abreu, MD¹, Ellen J. Scherl, MD², David S. Rowbotham, MD³, Silvio Danese, MD, PhD⁴, William J. Sandborn, MD⁵, Ye Miao, MS⁶, Hongyan Zhang, PhD⁶, Remo Panaccione, MD⁷, Waqqas Afif, MD⁸, Tadakazu Hisamatsu, MD, PhD⁹, Rupert W. Leong, MD¹⁰, Bruce E. Sands, MD, MS, FACG¹¹, Ramesh P. Arasaradnam, PhD¹², Colleen Marano, PhD⁶
¹The University of Miami Health System, Miami, FL; ²Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY; ³Auckland City Hospital, Auckland, Auckland, New Zealand; ⁴IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Molise, Italy; ⁵University of California San Diego, La Jolla, CA; ⁶Janssen Research & Development, LLC, Spring House, PA; ⁷University of Calgary, Calgary, AB, Canada; ⁸McGill University Health Centre, Montreal, PQ, Canada; ⁹Kyorin University School of Medicine, Tokyo, Tokyo, Japan; ¹⁰Concord Hospital and Macquarie University Hospital, Sydney, New South Wales, Australia; ¹¹Icahn School of Medicine at Mount Sinai, New York, NY; ¹²Warwick Medical School, University of Warwick & University Hospital Coventry, Coventry Warwickshire, England, United Kingdom

Introduction: Ustekinumab (UST) is an IL-12/23p40 inhibitor approved for treatment of Crohn’s disease and ulcerative colitis (UC). In the UNIFI maintenance study of patients (pts) with moderate to severe UC, > 90% of pts who achieved clinical response or remission at week (wk) 44 were not receiving corticosteroids, an important therapeutic goal. In this analysis, we describe the corticosteroid-sparing effects of UST treatment through 4 years (yrs) among pts who were treated in the UNIFI long-term extension (LTE).

Methods: Overall, 523 intravenous UST induction responders were randomized to subcutaneous (SC) maintenance therapy (placebo [PBO], n=175; UST 90mg every 12 wks [q12w], n=172; or UST 90mg q8w, n=176). A total of 284 UST pts completed wk44 and were treated in the LTE. PBO pts were discontinued after study unblinding. Based on investigator’s clinical judgement of UC disease activity, pts in the LTE were eligible to receive a dose adjustment starting at wk56: PBO to q8w, q12w to q8w, and q8w to q8w (sham adjustment). Pts in PBO or q8w groups were only eligible for dose adjustment or sham dose adjustment before unblinding. Efficacy was evaluated using symptomatic remission (Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0).

During the maintenance study, all pts receiving corticosteroids at maintenance baseline were required to initiate tapering. Through wk200 of the LTE, symptomatic remission endpoints were calculated with treatment failure and missing data nonresponder imputation, and dose adjustment was not considered to be a treatment failure. Missing corticosteroid dose data were managed using last observation carried forward.

Results: Of the 284 pts randomized to UST and treated in the LTE, 139 were receiving corticosteroids at maintenance baseline. Of these, 79.1% (n=110) were no longer receiving corticosteroids at wk200. Rates of corticosteroid-free symptomatic remission at wk200 were generally similar for the q8w and q12w maintenance doses (Table 1). Of the UST-treated pts in symptomatic remission at wk200, 94/96 (97.9%) in the q12w group and 91/96 (94.8%) in the q8w group were corticosteroid free.

Discussion: UST maintenance therapy, with both q8w and q12w dosing regimens, was effective in reducing and eliminating the use of corticosteroids in pts with UC through 4 yrs. The majority of pts in symptomatic remission were corticosteroid free through 4 yrs of treatment with UST.

Analysis	90mg UST SC q12w^a	90mg UST SC q8w^a	Combined UST^a
Randomized patients in maintenance who were treated in the LTE, N	141	143	284
Patients in symptomatic remission, n/N (%)^d,e,f
Week 44	117/141 (83.0)	119/143 (83.2)	236/284 (83.1)
Week 200	96/141 (68.1)	96/143 (67.1)	192/284 (67.6)
Patients in symptomatic remission and not receiving corticosteroids, n/N (%)^b,d,e,f
Week 44	111/141 (78.7)	115/143 (80.4)	226/284 (79.6)
Week 200	94/141 (66.7)	91/143 (63.6)	185/284 (65.1)
Patients in symptomatic remission and not receiving corticosteroids among patients receiving corticosteroids at maintenance baseline, n/N (%)^b,c,d,e,f
Week 44	49/68 (72.1)	56/71 (78.9)	105/139 (75.5)
Week 200	39/68 (57.4)	47/71 (66.2)	86/139 (61.9)
Patients who were able to eliminate the use of corticosteroids, n/N (%)^b,c
Week 44	61/68 (89.7)	64/71 (90.1)	125/139 (89.9)
Week 200	53/68 (77.9)	57/71 (80.3)	110/139 (79.1)
LTE, long-term extension; q8w, every 8 weeks; q12w, every 12 weeks; SC, subcutaneous; UST, ustekinumab. ^aRandomized group at maintenance Week 0 regardless of whether patients had a dose adjustment during the LTE. ^bPatients who had a missing value in corticosteroid use at the designated visit had their last available value carried forward to the designated visit. ^cDenominator is the number of patients who were receiving concomitant corticosteroids at maintenance baseline. ^dSymptomatic remission is defined as a stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0. ^ePatients who had both stool frequency and rectal bleeding subscores missing at a visit were considered not to be in symptomatic remission for that visit. ^fPatients who had an ostomy or colectomy, or discontinued study agent due to lack of therapeutic effect or due to an adverse event of worsening of ulcerative colitis prior to the designated visit were considered not to be in symptomatic remission.

Table: Table 1. Symptomatic remission and corticosteroid-sparing effects in patients who were randomized to UST in maintenance and were treated in the long-term extension

Disclosures:

Maria Abreu: AbbVie – Advisory Committee/Board Member, Consultant. Alimentiv – Speakers Bureau. Arena Pharmaceuticals – Advisory Committee/Board Member, Consultant. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant. Eli Lilly – Advisory Committee/Board Member, Consultant. Gilead – Advisory Committee/Board Member, Consultant. Intellisphere (HCP Live Institutional Perspectives in GI) – Speakers Bureau. Janssen – Speakers Bureau. Janssen Biotech (nonbranded) – Consultant. Janssen Biotech (Women in GI Advisory Board) – Advisory Committee/Board Member, Consultant. Janssen Biotech NART – Consultant. Janssen Global Services – Consultant. Janssen Ortho – Advisory Committee/Board Member, Consultant. Microba – Advisory Committee/Board Member, Consultant. Pfizer – Grant/Research Support. Prime CME – Speakers Bureau. Prometheus Biosciences – Advisory Committee/Board Member, Consultant, Grant/Research Support. Takeda – Grant/Research Support, Speakers Bureau. UCB Biopharma – Advisory Committee/Board Member, Consultant. WebMD Global – Advisory Committee/Board Member, Consultant.

Ellen Scherl: AbbVie – Consultant, Grant/Research Support. AstraZeneca – Grant/Research Support. Bristol Myers Squibb – Consultant. Celgene – Grant/Research Support. Crohn’s and Colitis Foundation – Consultant, Grant/Research Support. Entera Health – Consultant. Evidera – Consultant. Genentech – Grant/Research Support. GI Health Foundation – Consultant, Speakers Bureau. Gilead – Stock Options. Janssen Research & Development, LLC – Consultant, Grant/Research Support. Johns Hopkins University – Grant/Research Support. National Institute of Diabetes and Digestive and Kidney – Grant/Research Support. National Institute of Health – Grant/Research Support. New York Crohn’s Foundation – Grant/Research Support. Pfizer – Grant/Research Support. Protagonist – Consultant. Seres – Consultant, Grant/Research Support. Takeda – Consultant. UCB – Grant/Research Support.

David Rowbotham: AbbVie – Advisory Committee/Board Member, Speakers Bureau. Baxter – Advisory Committee/Board Member, Speakers Bureau. bioCSL – Speakers Bureau. Emerge Health – Speakers Bureau. Given Imaging – Speakers Bureau. Hospira – Advisory Committee/Board Member. Janssen Research & Development, LLC – Advisory Committee/Board Member, Speakers Bureau. Pharmaco – Advisory Committee/Board Member.

Silvio Danese: AbbVie – Consultant, Speakers Bureau. Allergan – Consultant, Speakers Bureau. Amgen – Consultant, Speakers Bureau. AstraZeneca – Consultant, Speakers Bureau. Athos Therapeutics – Consultant, Speakers Bureau. Biogen – Consultant, Speakers Bureau. Boehringer Ingelheim – Consultant, Speakers Bureau. Celgene – Consultant, Speakers Bureau. Celltrion – Consultant, Speakers Bureau. Eli Lilly – Consultant, Speakers Bureau. Enthera – Consultant, Speakers Bureau. Ferring – Consultant, Speakers Bureau. Gilead – Consultant, Speakers Bureau. Hospira – Consultant, Speakers Bureau. Inotrem – Consultant, Speakers Bureau. Janssen – Consultant, Speakers Bureau. Johnson & Johnson – Consultant, Speakers Bureau. MSD – Consultant, Speakers Bureau. Mundipharma – Consultant, Speakers Bureau. Mylan – Consultant, Speakers Bureau. Pfizer – Consultant, Speakers Bureau. Roche – Consultant, Speakers Bureau. Sandoz – Consultant, Speakers Bureau. Sublimity Therapeutics – Consultant, Speakers Bureau. Takeda – Consultant, Lecture fees. TiGenix – Consultant, Speakers Bureau. UCB Inc – Consultant, Speakers Bureau. Vifor – Consultant, Speakers Bureau.

William Sandborn: AbbVie – Consultant, Grant/Research Support. Abivax – Consultant. Admirx – Consultant. Alfa sigma – Consultant. Alimentiv (previously Robarts Clinical Trials, owned by Alimentiv Health Trust) – Consultant. Alivio Therapeutics – Consultant. Allakos – Consultant, Stock Options. Allergan – Consultant. Amgen – Consultant. Applied Molecular Transport – Consultant. Arena Pharmaceuticals – Consultant, Grant/Research Support. Avexegen Therapeutics – Consultant. Aviva – Grant/Research Support. Bausch Health (Salix) – Consultant. BeiGene – Consultant, Stock Options. Bellatrix Pharmaceuticals – Consultant. Boehringer Ingelheim – Consultant, Grant/Research Support. Boston Pharmaceuticals – Consultant. Bristol Myers Squibb – Consultant. Celgene – Consultant, Grant/Research Support. Celltrion – Consultant. Cellularity – Consultant. Conatus – Consultant. Cosmo Pharmaceuticals – Consultant. Equillium – Consultant. Escalier Biosciences – Consultant. Ferring – Consultant. Forbion – Consultant. Genentech – Grant/Research Support. Genentech/Roche – Consultant. Gilead Sciences – Consultant, Grant/Research Support. Glenmark Pharmaceuticals – Consultant. Gossamer Bio – Consultant, Stock Options. GSK – Grant/Research Support. Immunic (Vital Therapies) – Consultant. Incyte – Consultant. Index Pharmaceuticals – Consultant. Intact Therapeutics – Consultant. Janssen – Consultant, Grant/Research Support. Kyowa Kirin Pharmaceutical Research – Consultant. Kyverna Therapeutics – Consultant. Landos Biopharma – Consultant. Lilly – Consultant, Grant/Research Support. Miraca Life Sciences – Consultant. Nivalis Therapeutics – Consultant. Novartis – Consultant. Nutrition Science Partners – Consultant. Oppilan Pharma (acquired by Ventyx Biosciences) – Consultant, Stock Options. Otsuka – Consultant. Pandion Therapeutics – Consultant. Paul Hastings – Consultant. Pfizer – Consultant, Grant/Research Support. Progenity – Consultant, Stock Options. Prometheus Biosciences – Consultant, Grant/Research Support, Stock Options. Prometheus Laboratories – Consultant, Stock Options. Protagonist Therapeutics – Consultant. Provention Bio – Consultant. Reistone Biopharma – Consultant. Ritter Pharmaceuticals – Consultant. Seres Therapeutics – Consultant, Grant/Research Support. Shanghai Pharma Biotherapeutics – Consultant. Shire – Consultant, Grant/Research Support. Shoreline Biosciences – Consultant, Employee, Stock Options. Sienna Biopharmaceuticals – Consultant. Sigmoid Biotechnologies – Consultant. Sterna Biologicals – Consultant. Sublimity Therapeutics – Consultant. Surrozen – Consultant. Takeda – Consultant, Grant/Research Support. TheraVance Biopharma – Consultant, Grant/Research Support. Thetis Pharmaceuticals – Consultant. Tigenix – Consultant. Tillotts Pharma – Consultant. UCB Pharma – Consultant. Vendata Biosciences – Consultant. Ventyx Biosciences – Consultant, Stock Options. Vimalan Biosciences – Consultant, Stock Options. Vivelix Pharmaceuticals – Consultant. Vivreon Biosciences – Consultant, Stock Options. Zealand Pharma – Consultant.

Ye Miao: Janssen Research & Development, LLC – Employee, Stock-publicly held company(excluding mutual/index funds).

Hongyan Zhang: Johnson & Johnson – Employee, Stock-publicly held company(excluding mutual/index funds).

Remo Panaccione: Abbott – Consultant. AbbVie – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Alimentiv – Consultant. Amgen – Advisory Committee/Board Member, Consultant. Arena – Advisory Committee/Board Member, Consultant, Speakers Bureau. AstraZeneca – Consultant. Boehringer Ingelheim – Consultant. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant. Celgene – Advisory Committee/Board Member, Consultant, Speakers Bureau. Celltrion – Advisory Committee/Board Member, Consultant. Cosmos Pharmaceuticals – Consultant. Eisai – Consultant. Elan – Consultant. Eli Lilly – Advisory Committee/Board Member, Consultant, Speakers Bureau. Ferring – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Galapagos – Advisory Committee/Board Member, Consultant. Genentech – Advisory Committee/Board Member, Consultant. Gilead Sciences – Advisory Committee/Board Member, Consultant, Speakers Bureau. GlaxoSmithKline – Advisory Committee/Board Member, Consultant. Janssen – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Merck – Advisory Committee/Board Member, Consultant, Speakers Bureau. Mylan – Advisory Committee/Board Member, Consultant. Oppilan Pharma – Advisory Committee/Board Member, Consultant. Pandion Pharma – Advisory Committee/Board Member. Pandion Therapeutics – Consultant. Pfizer – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Progenity – Consultant. Protagonist Therapeutics – Consultant. Roche – Consultant, Speakers Bureau. Sandoz – Advisory Committee/Board Member, Consultant, Speakers Bureau. Satisfai Health – Consultant. Schering-Plough – Consultant. Shire – Advisory Committee/Board Member, Consultant, Speakers Bureau. Sublimity Therapeutics – Advisory Committee/Board Member, Consultant. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Theravance – Advisory Committee/Board Member, Consultant. UCB – Consultant.

Waqqas Afif: Janssen Research & Development, LLC – Grant/Research Support.

Tadakazu Hisamatsu: AbbVie – Consultant, Grant/Research Support, Lecture fees. Celgene – Consultant. Daiichi-Sankyo – Grant/Research Support. EA Pharma Co, Ltd – Consultant, Grant/Research Support, Lecture fees. Janssen Research & Development, LLC – Consultant, lecture fees. JIMRO – Grant/Research Support. JIMRO Co – Consultant, Grant/Research Support. Kyorin Pharmaceutical Co. Ltd – Consultant, Grant/Research Support. Mitsubishi Tanabe Pharma Corporation – Grant/Research Support, Lecture fees. Mochida Pharmaceutical Co., Ltd – Grant/Research Support, lecture fees. Nichi-Iko Pharmaceutical Co., Ltd – Consultant. Nippon Kayaku Co., Ltd – Grant/Research Support. Pfizer Inc – Consultant, Grant/Research Support, lecture fees. Takeda Pharmaceutical Co., Ltd – Grant/Research Support, Lecture fees. Zeria Pharmaceutical Co. Ltd – Grant/Research Support.

Rupert Leong: AbbVie – Consultant. Aspen – Consultant. Bristol Myers Squibb – Consultant. Celgene – Consultant. Chiesi – Consultant. Dr Falk Pharma – Consultant. Endochoice – Grant/Research Support. Ferring – Consultant, Grant/Research Support. GESA – Grant/Research Support. Glutagen – Consultant. Gutsy Group – Grant/Research Support. Hospira – Consultant. Janssen – Consultant, Grant/Research Support. MSD – Consultant. NHMRC – Grant/Research Support. Novartis – Consultant. Pfizer – Consultant, Grant/Research Support. Shire – Grant/Research Support. Takeda – Consultant, Grant/Research Support.

Bruce Sands: Abivax – Consultant, Speaking. Amgen – Consultant. Arena Pharmaceuticals – Consultant. Artugen Therapeutics – Consultant. AstraZeneca – Consultant. Bacainn Therapeutics – Consultant. Boehringer-Ingelheim – Consultant. Boston Pharmaceuticals – Consultant. Bristol Myers Squibb – Consultant, speaking, research funding. Calibr – Consultant. Celltrion Healthcare – Consultant. ClostraBio – Consultant. Eli Lilly and Company – Consultant. Entera – Consultant. Evommune – Consultant. Galapagos – Consultant. Genentech – Consultant. Gilead Sciences – Consultant. GlaxoSmithKline – Consultant. Gossamer Bio – Consultant. InDex Pharmaceuticals – Consultant. Innovation Therapeutics – Consultant. Inotrem – Consultant. Ironwood Pharmaceuticals – Consultant. Janssen – Consultant, Grant/Research Support, speaking. Kaleido – Consultant. Kallyope – Consultant. Miro Bio – Consultant. Morphic Therapeutics – Consultant. MRM Health – Consultant. Pfizer – Consultant, speaking. Progenity – Consultant. Prometheus Biosciences – Consultant. Protagonist Therapeutics – Consultant. Q32 Bio – Consultant. Surrozen – Consultant. Takeda – Consultant, Speaking. Teva – Consultant. TLL Pharmaceutical – Consultant. USWM Enterprises – Consultant. VielaBio – Consultant.

Ramesh Arasaradnam: AbbVie – Consultant, Grant/Research Support. Dr Falk Pharma – Consultant, Grant/Research Support. Janssen Research & Development, LLC – Consultant, Grant/Research Support.

Colleen Marano: Janssen Research & Development, LLC – Employee, Stock-publicly held company(excluding mutual/index funds).