P2174 - Analysis of Baseline Characteristics Associated With Clinical Response to Ustekinumab IV Re-induction Strategy in Patients With Crohn’s Disease in the POWER Trial

Monday, October 23, 2023

10:30 AM – 4:15 PM PT

Location: Exhibit Hall

Presenting Author(s)

Douglas C. C. Wolf, MD

Atlanta Gastroenterology Associates
Atlanta, Georgia

Award: Presidential Poster Award

Douglas C.. Wolf, MD¹, Scott D. Lee, MD², Stefan Schreiber, MD³, C. Janneke van der Woude, MD, PhD⁴, Ignacio Marín-Jiménez, MD⁵, Elisabeth Schnoy, MD, PhD⁶, Bruce Salzberg, MD⁷, Christopher Busse, ⁸, Maciej Nazar, ⁹, Wayne Langholff, ¹⁰, Christopher Gasink, ⁸, Thomas Baker, ¹⁰, Bridget Godwin, MD⁸, Brian G. Feagan, MD¹¹
¹Atlanta Gastroenterology Associates, Atlanta, GA; ²University of Washington, Seattle, WA; ³University Hospital Schleswig-Holstein, Kiel, Schleswig-Holstein, Germany; ⁴Erasmus University Medical Center, Rotterdam, Drenthe, Netherlands; ⁵Hospital Universitario Gregorio Marañón, IiSGM, Rotterdam, Zuid-Holland, Netherlands; ⁶University Hospital of Augsburg, Augsburg, Bayern, Germany; ⁷Atlanta Gastroenterology Specialists PC, IBD Center of Atlanta, Atlanta, GA; ⁸Janssen Scientific Affairs, LLC, Horsham, PA; ⁹Janssen-Cilag Polska Sp. z o.o, Warsaw, Mazowieckie, Poland; ¹⁰Janssen Research & Development, LLC, Spring House, PA; ¹¹Western University, London, ON, Canada

Introduction: The 36-week (W) POWER trial evaluated the efficacy and safety of a single intravenous (IV) re-induction ustekinumab (UST) dose vs continued UST subcutaneous (SC) treatment in Crohn’s disease (CD) patients with secondary loss of response (LoR) to standard UST maintenance therapy. Here, we report subgroup analysis of the primary endpoint by baseline characteristics.

Methods: Adults with moderately–severely active CD who initially responded to UST IV induction therapy per label and later experienced LoR were included. LoR has been previously defined¹. At baseline (W0), randomized patients received ~6mg/kg IV UST/SC placebo (IV arm) or IV placebo/SC UST 90mg (SC arm), followed by SC UST 90mg dosing at W8/16. Descriptive statistics were used to summarize baseline characteristics. Clinical assessments occurred at W0/8/16. Primary endpoint: clinical response (CRes; decrease of ≥100 points from W0 in CD activity index [CDAI] or CDAI < 150 ) at W16. Odds ratios (ORs), confidence intervals (CIs) and p-values were estimated with a logistic regression model.

Results: The full analysis set comprised 215 patients at W0 (SC, n=107; IV, n=108). At W16, 86.0% (SC) and 92.6% (IV) of patients completed treatment. At W16, 37.4% (SC) and 49.1% (IV) of patients achieved CRes (p=0.089). Of all baseline characteristics, disease location and duration, inflammatory biomarkers and prior biologic failures were of particular interest (Table). A greater proportion of patients from the IV vs SC arm achieved CRes at W16 (OR 3.6; 95%CI 1.6–8.1; p=0.002) of those with ileum and colon involvement. Patients with disease duration of < 5 years in the IV (n=22) vs SC (n=20) arm were more likely to achieve W16 CRes (OR 4.5; 95%CI 1.2–17.4; p=0.029). A greater proportion of patients in the IV vs SC arm with elevated baseline C-reactive protein (OR 2.1; 95%CI 1.1–4.0; p=0.029) or fecal calprotectin (OR 2.0; 95%CI 1.0–4.0; p=0.045) achieved W16 CRes as did patients with 1 prior biologic failure (OR 2.8; 95%CI 1.0–7.6; p=0.042).

Discussion: POWER assessed the efficacy and safety of UST IV re-induction in patients with LoR during UST maintenance therapy. This analysis suggests that patients with fewer prior biologic exposures and shorter disease duration but a higher disease burden at baseline including greater disease extent involving ileum and colon, or elevated inflammatory biomarkers, are more likely to benefit from UST IV re-induction therapy.

1. S.W. Schreiber, et al. J Crohns Colitis. 2023;17(Suppl 1):571 (Abstract P436).

Baseline and clinical disease characteristics	UST SC (n=107), n/N (%)	UST IV (n=108), n/N (%)	OR^‡ (95%CI); p-value
Age (median years) ≤40 >40	22/62 (35.5) 18/45 (40.0)	28/52 (53.8) 25/56 (44.6)	2.1 (1.0; 4.4); p=0.060 1.3 (0.6; 2.8); p=0.587
CDAI Score ≤300 >300	24/68 (35.3) 16/39 (41.0)	30/68 (44.1) 23/40 (57.5)	1.4 (0.7; 2.9); p=0.312 2.0 (0.8; 4.8); p=0.138
Prior CD-related surgery history Total or subtotal colectomy Partial bowel resection Current draining fistula Prior perianal surgery	4/9 (44.4) 12/28 (42.9) 2/10 (20.0) 4/21 (19.0)	7/17 (41.2) 21/39 (53.8) 4/11 (36.4) 14/23 (60.9)	NE 1.5 (0.5; 4.0); p=0.472 NE 5.8 (1.5; 23.3); p=0.013
Involved gastrointestinal areas Ileum only Colon only Ileum and colon	13/28 (46.4) 11/22 (50.0) 16/55 (29.1)	10/29 (34.5) 10/24 (41.7) 33/55 (60.0)	0.6 (0.2; 2.0); p=0.434 0.7 (0.2; 2.3); p=0.505 3.6 (1.6; 8.1); p=0.002
Disease duration (years) < 5 ≥5	5/20 (25.0) 35/87 (40.2)	13/22 (59.1) 40/86 (46.5)	4.5 (1.2; 17.4); p=0.029 1.3 (0.7; 2.4); p=0.395
Prior failed biologics 0 1 2 3 4	1/8 (12.5) 15/37 (40.5) 13/35 (37.1) 10/25 (40.0) 1/2 (50.0)	5/12 (41.7) 21/33 (63.6) 18/35 (51.4) 6/23 (26.1) 3/5 (60.0)	NE 2.8 (1.0; 7.6); p=0.042 2.0 (0.7; 5.3); p=0.173 0.6 (0.2, 2.0); p=0.363 NE
Baseline biomarker levels CRP ≤3 mg/L CRP >3 mg/L fCal ≤250 mg/kg fCal >250 mg/kg	12/32 (37.5) 28/75 (37.3) 16/32 (50.0) 24/75 (32.0)	10/29 (34.5) 43/79 (54.4) 18/35 (51.4) 35/73 (47.9)	0.9 (0.3; 2.5); p=0.780 2.1 (1.1; 4.0); p=0.029 1.1 (0.4; 2.8); p=0.920 2.0 (1.0; 4.0); p=0.045

Disclosures:

Douglas Wolf: AbbVie – Advisory Committee/Board Member, Consultant, Speakers Bureau. Arena – Advisory Committee/Board Member, Consultant, Speakers Bureau. Celgene/Bristol Myers Squibb – Advisory Committee/Board Member, Consultant, Speakers Bureau. Janssen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Pfizer – Advisory Committee/Board Member, Consultant, Speakers Bureau. Takeda – Advisory Committee/Board Member, Consultant, Speakers Bureau.

Scott Lee: AbbVie – Grant/Research Support. AbGenomics – Grant/Research Support. Applied Molecular Transport, Arena, Boehringer Ingelheim – Consultant. Arena – Grant/Research Support. Bridge Biotherapeutics – Consultant. Bristol-Myers Squibb – Consultant. Celgene – Consultant. Celgene – Grant/Research Support. Celltrion Healthcare – Consultant. Celltrion Healthcare – Grant/Research Support. Cornerstones Health – Consultant. Eli Lilly and Company – Consultant. Janssen – Consultant. Janssen – Grant/Research Support. KCRN Research – Consultant. Salix – Grant/Research Support. Samsung Bioepis and UCB – Consultant. Takeda – Grant/Research Support. UCB – Grant/Research Support.

Stefan Schreiber: AbbVie – Personal fees. Amgen – Personal fees. Arena Pharmaceuticals – Personal fees. Biogen – Personal fees. Bristol Myers Squibb – Personal fees. Celgene – Personal fees. Celltrion Healthcare – Personal fees. Dr. Falk Pharma – Personal fees. Eli Lilly – personal fees. Ferring Pharmaceuticals – personal fees. Fresenius Kabi – Personal fees. Galapagos – Personal fees. Gilead – Personal fees. Hikma Pharmaceuticals – Personal fees. I-Mab – Personal fees. Janssen Pharmaceuticals – Personal fees. Morphic – Personal fees. MSD – Personal fees. Mylan – Personal fees. Pfizer – Personal fees. Protagonist – Personal fees. ProventionBio – Personal fees. Sandoz/Hexal – personal fees. Takeda – Personal fees. Theravance Biopharma – Personal fees. UCB – personal fees.

C. Janneke van der Woude: AbbVie – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. Celltrion – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. Dr. Falk Pharma Benelux – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. Falk Ben-elux – Grant/Research Support. Ferring – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. Janssen – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. Pfizer – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. Takeda – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau.

Ignacio Marín-Jiménez: Abbvie – Advisory Committee/Board Member, Consultant, Grant/Research Support. Chiesi – Advisory Committee/Board Member, Consultant, Grant/Research Support. Faes Farma – Advisory Committee/Board Member, Consultant, Grant/Research Support. FalkPharma – Advisory Committee/Board Member, Consultant, Grant/Research Support. Ferring – Advisory Committee/Board Member, Consultant, Grant/Research Support. Gebro Pharma – Advisory Committee/Board Member, Consultant, Grant/Research Support. Hospira – Advisory Committee/Board Member, Consultant, Grant/Research Support. Janssen – Advisory Committee/Board Member, Consultant, Grant/Research Support. MSD – Advisory Committee/Board Member, Consultant, Grant/Research Support. Otsuka Pharmaceutical – Advisory Committee/Board Member, Consultant, Grant/Research Support. Pfizer – Advisory Committee/Board Member, Consultant, Grant/Research Support. Shire – Advisory Committee/Board Member, Consultant, Grant/Research Support. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support. Tillots – Advisory Committee/Board Member, Consultant, Grant/Research Support. UCB Pharma – Advisory Committee/Board Member, Consultant, Grant/Research Support.

Elisabeth Schnoy: AbbVie – personal fees. Bristol Myers Squibb – personal fees. Celltrion Healthcare – personal fees. Dr. Falk Pharma – personal fees. Galapagos/Gilead – personal fees. I-Mab – personal fees. Janssen – personal fees. Lilly – personal fees. Pfizer – personal fees. Pharmacosmos – personal fees. Takeda – personal fees. Tillotts Pharma – personal fees.

Bruce Salzberg: AbbVie – honoraria as a speaker. Bristol-Myers Squibb – honoraria as a speaker. Johnson and Johnson – Consultant. Johnson and Johnson – honoraria as a speaker.

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

Maciej Nazar: Janssen-Cilag Polska Sp. z o.o. – Employee, Stock-publicly held company(excluding mutual/index funds).

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

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

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

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

Brian Feagan: AbbVie – Advisory Committee/Board Member, Consultant, Speakers Bureau. AbolerIS – Consultant. AgomAB Therapeutics – Consultant. Allianthera – Consultant. Amgen – Advisory Committee/Board Member, Consultant. AnaptysBio – Consultant. Applied Molecular Transport Inc. – Consultant. Arena Pharma – Consultant. Avir – Consultant. Azora Therapeutics – Consultant. Baxter – Consultant. BioJamp – Consultant. Biora Therapeutics – Consultant. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant. Boston Pharma – Consultant. Bristol Myers Squibb – Consultant. Celgene/BMS – Advisory Committee/Board Member, Consultant. Connect BioPharma – Consultant. Cytoki – Consultant. Disc Medicine – Consultant. Duality – Consultant. EcoR1 – Advisory Committee/Board Member, Consultant. Eli Lilly – Consultant. Equillium – Consultant. Ermium – Consultant. Everest Clinical Research Corp. – Consultant. Ferring Pharmaceuticals – Consultant. First Wave – Consultant. Galapagos – Consultant. Galen Atlantica – Consultant. Genentech/Roche – Advisory Committee/Board Member, Consultant. Gilead – Consultant. GlaxoSmithKline – Advisory Committee/Board Member, Consultant. Glenmark – Consultant. Gossamer Pharma – Consultant, stock shareholder. Hoffmann-LaRoche – Consultant. Hot Spot Therapeutics – Consultant. Imhotex – Consultant. ImmunExt – Consultant. Immunic Therapeutics – Consultant. Index Pharma – Advisory Committee/Board Member, Consultant. Intact Therapeutics – Consultant. JAKAcademy – Consultant. Janssen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Japan Tobacco Inc. – Consultant. Kaleido Biosciences – Consultant. L.E.K. Consulting – Consultant. Landos Biopharma – Consultant. Leadiant – Consultant. LifeSci Capital – Consultant. Lument AB – Consultant. Millennium – Consultant. MiroBio – Consultant. Morphic Therapeutics – Advisory Committee/Board Member, Consultant. Mylan – Consultant. Novartis – Advisory Committee/Board Member. OM Pharma – Consultant. Origo BioPharma – Advisory Committee/Board Member, Consultant. Orphagen – Consultant. Otsuka – Consultant. Pandion Therapeutics – Consultant. Pfizer – Advisory Committee/Board Member, Consultant. Play to Know AG – Consultant. Progenity – Advisory Committee/Board Member, Consultant. Prometheus Therapeutics and Diagnostics – Advisory Committee/Board Member, Consultant. Protagonist – Consultant. PTM Therapeutics – Consultant. Q32 Bio – Consultant. Rebiotix – Consultant. RedHill Biopharma – Consultant. Redx – Consultant. Roche – Consultant. Sandoz – Consultant. Sanofi – Consultant. Seres Therapeutics – Consultant. Silverback Therapeutics – Consultant. Surrozen Inc. – Consultant. Takeda – Advisory Committee/Board Member, Consultant, Speakers Bureau. Teva – Advisory Committee/Board Member, Consultant. Thelium – Consultant. Theravance – Consultant. Tigenix – Consultant. Tillotts Pharma – Advisory Committee/Board Member, Consultant. UCB Pharma – Consultant. VHSquared Ltd. – Consultant. Viatris – Consultant. Western University, Alimentiv Inc – Employee. Ysios – Consultant. Ysopia – Consultant. Zealand Pharma – Consultant.

Douglas C.. Wolf, MD¹, Scott D. Lee, MD², Stefan Schreiber, MD³, C. Janneke van der Woude, MD, PhD⁴, Ignacio Marín-Jiménez, MD⁵, Elisabeth Schnoy, MD, PhD⁶, Bruce Salzberg, MD⁷, Christopher Busse, ⁸, Maciej Nazar, ⁹, Wayne Langholff, ¹⁰, Christopher Gasink, ⁸, Thomas Baker, ¹⁰, Bridget Godwin, MD⁸, Brian G. Feagan, MD¹¹. P2174 - Analysis of Baseline Characteristics Associated With Clinical Response to Ustekinumab IV Re-induction Strategy in Patients With Crohn’s Disease in the POWER Trial, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.