41 - The Effect of Guselkumab Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Results at Week 12 by Prior Inadequate Response or Intolerance to Advanced Therapy

Tuesday, October 25, 2022

2:55 PM – 3:05 PM ET

Location: Hall C2

Presenting Author(s)

David T. Rubin, MD, FACG

University of Chicago Medicine Inflammatory Bowel Disease Center
Chicago, IL

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David T. Rubin, MD, FACG¹, Jessica R. Allegretti, MD, MPH², Bruce E. Sands, MD, MS, FACG³, Kuan-Hsiang Huang, MD, PhD⁴, Mary Kavalam, RN, EdD⁴, Matthew Germinaro, MD⁵, Rebbecca Wilson, DPH⁴, Hongyan Zhang, PhD⁴, Emese Mihály, MD, PhD⁶, Tadakazu Hisamatsu, MD, PhD⁷, Axel Dignass, MD, PhD⁸, Julian Panés, MD⁹
¹University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL; ²Brigham and Women’s Hospital Crohn’s and Colitis Center, Boston, MA; ³Icahn School of Medicine at Mount Sinai, New York, NY; ⁴Janssen Research & Development, LLC, Spring House, PA; ⁵Janssen Research & Development, LLC., Spring House, PA; ⁶Semmelweis University, Budapest, Budapest, Hungary; ⁷Kyorin University School of Medicine, Tokyo, Tokyo, Japan; ⁸Agaplesion Markus Hospital / Goethe University, Frankfurt, Hessen, Germany; ⁹Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Catalonia, Spain

Introduction: QUASAR (NCT04033445) is a phase 2b randomized, double-blind, placebo-controlled study that evaluates guselkumab (GUS), an interleukin-23 p19 subunit antagonist, as induction treatment in patients with moderately to severely active ulcerative colitis (UC) who had an inadequate response or intolerance to conventional (ie, thiopurines or corticosteroids) or advanced therapy (ADT; ie, tumor necrosis factor alpha antagonists, vedolizumab, or tofacitinib). Here we report efficacy results at Week 12 by prior inadequate response or intolerance to ADT.

Methods: Patients included had moderately to severely active UC (defined as a modified Mayo score of 5 to 9 with a Mayo rectal bleeding subscore ≥ 1 and a Mayo endoscopy subscore ≥ 2 obtained during central review of video endoscopy at baseline). Patients were randomized 1:1:1 to receive IV GUS 400 mg, 200 mg, or placebo at Weeks 0, 4, and 8. At Week 12, clinical response, clinical remission, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, and endoscopic normalization were compared for GUS vs placebo by prior response/intolerance to ADT.

Results: Three hundred thirteen patients were assessed; 148 patients (47.3%) had prior inadequate response/intolerance to ADT, approximately half of these patients had prior inadequate response/intolerance to 2 or more ADT classes. Clinical response at Week 12 was achieved by a higher proportion of patients treated with GUS vs placebo: 50.5% vs 25.5% for patients with prior inadequate response/intolerance to ADT and 70.3% vs 29.6% for those without prior inadequate response/intolerance to ADT. Higher proportions of patients treated with GUS vs placebo achieved clinical and endoscopic/histologic outcomes at Week 12 in both the ADT inadequate response/intolerant and non-ADT inadequate response/intolerant populations (Table 1). The efficacy of IV GUS 200 mg and 400 mg was comparable in patients with or without a history of inadequate response/intolerance to ADT.

Discussion: Treatment with GUS resulted in greater improvements compared with placebo across key clinical and endoscopic/histologic outcome measures at Week 12 in patients with moderately to severely active UC with or without a history of inadequate response/intolerance to ADT.

	Placebo IV (N=105)	GUS 200 mg IV (N=101)	GUS 400 mg IV (N=107)	GUS Combined (N=208)
Patients with a history of inadequate response/intolerance to ADT	51	46	51	97
Clinical response ^a1,b,c,d,e (95% CI)	25.5% (14.3, 39.6)	54.3% * (39.0, 69.1)	47.1%* (32.9, 61.5)	50.5%* (40.2, 60.8)
Clinical remission ^a2,b,c,d,e (95% CI)	7.8% (2.2, 18.9)	17.4% (7.8, 31.4)	17.6% (8.4, 30.9)	17.5% (10.6, 26.6)
Symptomatic remission ^a3,b,c,d,e (95% CI)	17.6% (8.4, 30.9)	39.1%* (25.1, 54.6)	37.3%* (24.1, 51.9)	38.1%* (28.5, 48.6)
Endoscopic improvement ^a4,b,c,d,e (95% CI)	9.8% (3.3, 21.4)	23.9% (12.6, 38.8)	21.6% (11.3, 35.3)	22.7% (14.8, 32.3)
Histo-endoscopic mucosal improvement ^a5,b,c,d,e (95% CI)	5.9% (1.2, 16.2)	13.0% (4.9, 26.3)	19.6%* (9.8, 33.1)	16.5% (9.7, 25.4)
Endoscopic normalization ^a6,b,c,d,e (95% CI)	5.9% (1.2, 16.2)	10.9% (3.6, 23.6)	5.9% (1.2, 16.2)	8.2% (3.6, 15.6)
Patents with no history of inadequate response/intolerance to ADT	54	55	56	111
Clinical response^a1,b,c,d,e (95% CI)	29.6% (18.0, 43.6)	67.3%** (53.3, 79.3)	73.2%** (59.7, 84.2)	70.3%** (60.9, 78.6)
Clinical remission^a2,b,c,d,e (95% CI)	11.1% (4.2, 22.6)	32.7%* (20.7, 46.7)	32.1%* (20.3, 46.0)	32.4%* (23.9, 42.0)
Symptomatic remission^a3,b,c,d,e (95% CI)	22.2% (12.0, 35.6)	58.2%** (44.1, 71.3)	57.1%** (43.2, 70.3)	57.7%** (47.9, 67.0)
Endoscopic improvement ^a4,b,c,d,e (95% CI)	14.8% (6.6, 27.1)	36.4%* (23.8, 50.4)	39.3%* (26.5, 53.2)	37.8%* (28.8, 47.5)
Histo-endoscopic mucosal improvement^a5,b,c,d,e (95% CI)	11.1% (4.2, 22.6)	27.3%* (16.1, 41.0)	33.9%* (21.8, 47.8)	30.6%* (22.2, 40.1)
Endoscopic normalization^a6,b,c,d,e (95% CI)	7.4% (2.1, 17.9)	23.6%* (13.2, 37.0)	21.4%* (11.6, 34.4)	22.5%* (15.1, 31.4)
Nominal p-value < 0.05. *Nominal p-value < 0.001. ^a1Clinical response is defined as decrease from induction baseline in the modified Mayo score by ≥30% and ≥2 points, with either a ≥1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1. ^a2 Clinical remission is defined as stool frequency subscore of 0 or 1 with no increase from induction baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. ^a3 Symptomatic remission is defined as a stool frequency subscore of 0 or 1 with no increase from induction baseline and a rectal bleeding subscore of 0. ^a4Endoscopic improvement is defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. ^a5Histo-endoscopic mucosal improvement is defined as achieving a combination of histologic improvement (neutrophil infiltration in < 5% of crypts, no crypt destruction, and no erosions, ulcerations or granulation tissue according to the Geboes grading system) and endoscopic improvement, ^a6Endoscopic normalization is defined as an endoscopy subscore of 0. ^b Patients who had a prohibited change in UC medication, an ostomy or colectomy, or discontinued study agent due to lack of efficacy or an adverse event of worsening of UC prior to the Week 12 visit were considered not to have achieved the endpoint. ^c Data after discontinuation of study agent due to COVID-19 related reasons (excluding COVID-19 infection) were considered to be missing. ^dPatients who were missing one or more components pertaining to a specified endpoint at Week 12 were considered not to have achieved the endpoint. ^eThe p-values were based on the Cochran-Mantel-Haenszel (CMH) chi-square test.

Table: Table 1. Efficacy at Week 12 by prior response/intolerance to ADT

Disclosures:

David Rubin: AbbVie – Consultant. Alimentiv Inc. – Consultant. AltruBio – Consultant. Arena Pharmaceuticals – Consultant. Aslan Pharmaceuticals – Consultant. Athos Therapeutics – Consultant. Bellatrix Pharmaceuticals – Consultant. Boehringer Ingelheim, Ltd. – Consultant. Bristol Myers Squibb – Consultant. Celgene Corp/Syneos – Consultant. ClostraBio – Consultant. Connect BioPharma – Consultant. EcoR1 – Consultant. Genentech/Roche – Consultant. Gilead Sciences – Consultant. Ironwood Pharmaceuticals – Consultant. Iterative Scopes – Consultant. Janssen – Consultant. Kaleido Biosciences – Consultant. Lilly, Eli & Co – Consultant. Materia Prima – Consultant. Pfizer – Consultant. Prometheus Biosciences – Consultant. Reistone Biopharma – Consultant. Seres Therapeutics, Inc – Consultant. Takeda – Consultant, Grant/Research Support. Target RWE – Consultant. Techlab – Consultant. Trellus Health – Consultant.

Jessica Allegretti: Artugen – Consultant. Baccain – Consultant. Bristol Myers Squibb – Consultant, Speaker. Ferring Pharmaceuticals – Consultant. Finch Therapeutics – Consultant, Grant/Research Support. Iterative Scopes – Consultant. Janssen – Consultant, Grant/Research Support. Merck – Grant/Research Support. Morphic – Consultant. Pfizer – Consultant, Grant/Research Support. Seres Therapeutics – Consultant. Servatus – Consultant. Takeda – Consultant.

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.

Kuan-Hsiang Huang: Johnson & Johnson – Employee, Stock-publicly held company(excluding mutual/index funds).

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

Matthew Germinaro: Janssen Research & Development – Employee. Johnson & Johnson – Stock-publicly held company(excluding mutual/index funds).

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

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

Emese Mihály: Abbvie – Lecture fees. Abivax – Grant/Research Support. Amgen – Grant/Research Support. Berlin-Chemie – Lecture fees. Boehringer-Ingelheim – Grant/Research Support. Bristol Myers Squibb – Grant/Research Support. Celgene – Grant/Research Support. Dr. Falk Pharma – Grant/Research Support. F.Hoffmann-La Roche – Grant/Research Support. Gilead – Grant/Research Support. Goodwill – Lecture fees. Janssen – Grant/Research Support, Lecture fees. Lilly – Grant/Research Support. Linical – Grant/Research Support. Pfizer – Grant/Research Support, Lecture fees. Roche – Lecture fees. Takeda – Grant/Research Support. Theravance Biopharma R&D – 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.

Axel Dignass: AbbVie – Consultant, Speakers Bureau. Abivax – Consultant. Amgen – Consultant. Biogen – Consultant. Boehringer Ingelheim – Consultant. Celgene/Bristol Myers Squibb – Consultant. Eli Lilly – Consultant, Speakers Bureau. Falk Foundation – Consultant, Speakers Bureau. Ferring – Consultant, Speakers Bureau. Fresenius Kabi – Consultant. Galapagos – Consultant, Speakers Bureau. Gilead – Consultant, Speakers Bureau. Janssen – Consultant, Speakers Bureau. MSD – Consultant, Speakers Bureau. Pfizer – Consultant, Speakers Bureau. Pharmacosmos – Consultant. Roche/Genentech – Consultant. Sandoz/Hexal – Consultant. Takeda – Consultant, Speakers Bureau. Tillotts – Consultant, Speakers Bureau. Vifor – Consultant, Speakers Bureau.

Julian Panés: Abbott – payment for the development of educational presentations, Speakers Bureau. AbbVie – Consultant, Grant/Research Support, support for travel to meetings, during the conduct of the study; payment for development of educational presentations. Arena – Consultant. Athos – Consultant. Boehringer Ingelheim – Consultant. Celgene – Consultant. Celltrion – Consultant. Ferring – Consultant. Galapagos – Consultant. Genentech-Roche – Consultant. GSK – Consultant. Janssen – Consultant, Payment for development of educational presentations, Speakers Bureau. Mirum – Consultant. Morphic – Consultant. MSD – Consultant. Nestlé – Consultant. Origo – Consultant. Pandion – Consultant. Pfizer – Consultant, Grant/Research Support, Payment for development of educational presentations, Speakers Bureau. Progenity – Consultant. Protagonist – Consultant. Revolo – Consultant. Robarts – Consultant. Roche – Payment for development of educational presentations. Takeda – Consultant, Support for travel to meetings during the conduct of the study, Speakers Bureau. Theravance – Consultant, Speakers Bureau. Wassermann – Consultant.