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Poster Session D - Tuesday Morning

Category: IBD

D0383 - Baseline and Early Predictors of Response to Risankizumab Induction and Maintenance Treatment in Patients With Moderate to Severe Crohn's Disease

Tuesday, October 25, 2022

10:00 AM – 12:00 PM ET

Location: Crown Ballroom

Has Audio

Presenting Author(s)

Javier Zambrano, MD

AbbVie, Inc.
North Chicago, Illinois

Jean-Frederic Colombel, MD¹, Walter Reinisch, MD, PhD², Stefan Schreiber, MD³, Silvio Danese, MD, PhD⁴, Ken Sugimoto, MD⁵, Maria T. Abreu, MD⁶, Naomi Martin, MD⁷, Kristina Kligys, PhD⁷, Valerie Pivorunas, PhD⁷, Alexandra Song, MD⁷, Javier Zambrano, MD⁷, Yafei Zhang, PhD⁷, Remo Panaccione, MD⁸
¹Icahn School of Medicine at Mount Sinai, New York, NY; ²Medical University of Vienna, Vienna, Wien, Austria; ³University Hospital Schleswig-Holstein, Kiel University, Kiel, Schleswig-Holstein, Germany; ⁴IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Molise, Italy; ⁵Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan; ⁶The University of Miami Health System, Miami, FL; ⁷AbbVie, Inc., North Chicago, IL; ⁸University of Calgary, Calgary, AB, Canada

Introduction: Pivotal phase 3 induction (ADVANCE and MOTIVATE) and maintenance (FORTIFY) studies established that treatment with risankizumab (RZB), a humanized monoclonal antibody with high specificity for the p19 subunit of interleukin-23, was superior to placebo for achieving clinical remission and endoscopic response in patients with moderate to severe Crohn's disease (CD). This exploratory analysis aimed to determine predictors of response to risankizumab induction and maintenance therapy.

Methods: Pooled data from patients in the RZB 600 mg intravenous (IV) dosing groups in ADVANCE + MOTIVATE induction studies (n=527) and data from the RZB 360 mg subcutaneous (SC) dosing group in FORTIFY (n=141) were evaluated. Multivariate logistic regression models were used to determine predictors of clinical and endoscopic outcomes at Weeks 12 and 52. For FORTIFY, separate logistic regression models were used to access end-of-induction characteristics for the achievement of outcomes at Week 52.

Results: Baseline characteristics found to be predictive of clinical and/or endoscopic outcomes at Week 12 and Week 52 are highlighted in the table. Age and duration of disease were evaluated but were not predictive. Compared to patients with ileal disease, patients with colonic disease were more likely to achieve endoscopic endpoints at Week 12, while patients with ileal-colonic disease were more likely to achieve endoscopic response at Week 12; patients with either colonic or ileal-colonic disease were more likely to achieve endoscopic response at Week 52. Conversely, patients with prior bio-failure at BL were less likely to achieve endoscopic response at Week 12, and clinical and endoscopic responses at Week 52. Patients using corticosteroids at BL were less likely to achieve clinical endpoints at Weeks 12 and 52. Patients achieving clinical or endoscopic endpoints at Week 12 were more likely to achieve these endpoints at Week 52.

Discussion: For patients treated with risankizumab, baseline disease location predicted achievement of endoscopic responses, corticosteroid use predicted achievement of clinical endpoints, and prior bio-failure status predicted achievement of both clinical and endoscopic endpoints at Week 52. Notably, achievement of clinical or endoscopic outcomes after induction with risankizumab were associated with a higher likelihood of achieving long-term clinical and endoscopic outcomes.

Week 12

SF/APS Clinical Remission

RZB 600 mg IV

Week 12

CDAI Clinical Remission

RZB 600 mg IV

Week 12

CDAI Clinical Response

RZB 600 mg IV

Week 12

Endoscopic Response

RZB 600 mg IV

Week 12

Endoscopic Remission

RZB 600 mg IV

Week 12

Ulcer-free Endoscopy

RZB 600 mg IV

Week 52

SF/APS Clinical Remission

RZB 360 mg SC

Week 52

CDAI Clinical Remission

RZB 360 mg SC

Week 52

CDAI Clinical Response

RZB 360 mg SC

Week 52

Endoscopic Response

RZB 360 mg SC

Week 52

Endoscopic Remission

RZB 360 mg SC

Week 52

Ulcer-free Endoscopy

RZB 360 mg SC

Induction Baseline Characteristics as Predictors of Response

Odds Ratio

[95% CI]

P-value

Colonic Disease Only

1.436 [0.766, 2.693]

P=0.260

1.653 [0.883, 3.094]

P=0.116

1.448 [0.774, 2.709]

P=0.247

5.178 [2.411, 11.123] P< 0.001

3.077 [1.425, 6.644]

P=0.004

3.393 [1.510, 7.624]

P=0.003

0.654 [0.265, 1.614]

P=0.357

0.886 [0.357, 2.203]

P=0.795

0.938 [0.378, 2.328]

P=0.890

4.909 [1.468, 16.410]

P=0.010

2.135 [0.722, 6.317]

P=0.170

2.428

[0.731, 8.060]

P=0.147

Ileal-colonic Disease Only

0.751 [0.411, 1.370] P=0.350

0.821 [0.451, 1.492] P=0.517

0.906 [0.506, 1.622] P=0.739

2.880 [1.379, 6.017] P=0.005

1.262 [0.590, 2.702] P=0.548

0.767

[0.331, 1.775] P=0.535

0.634 [0.263, 1.529] P=0.311

1.032 [0.426, 2.503] P=0.944

0.806 [0.333, 1.952] P=0.632

4.351 [1.318, 14.366] P=0.016

1.826 [0.627, 5.321] P=0.270

2.018 [0.617, 6.602] P=0.246

Bio-Failure Status

0.675 [0.423, 1.076] P=0.098

0.789 [0.495, 1.258] P=0.320

0.867 [0.540, 1.393] P=0.556

0.438 [0.271, 0.709] P< 0.001

0.597 [0.352, 1.013] P=0.056

0.570 [0.317, 1.026] P=0.061

0.425 [0.229, 0.787] P=0.006

0.373 [0.200, 0.698] P=0.002

0.426 [0.225, 0.805] P=0.009

0.443 [0.233, 0.844] P=0.013

0.444 [0.228, 0.863] P=0.017

0.295 [0.144, 0.606] P< 0.001

Corticosteroid Use

0.506 [0.321, 0.799] P=0.003

0.491 [0.313, 0.769] P=0.002

0.440 [0.283, 0.683] P< 0.001

0.742 [0.466, 1.181] P=0.208

0.786 [0.463, 1.334] P=0.372

0.891 [0.493, 1.609] P=0.701

0.443 [0.243, 0.805] P=0.008

0.331 [0.178, 0.613] P< 0.001

0.374 [0.210, 0.668] P< 0.001

0.796 [0.430, 1.474] P=0.468

0.787 [0.403, 1.539] P=0.485

0.939 [0.450, 1.959] P=0.866

Induction Week 12 Clinical Outcomes as Predictors of Response at Maintenance Week 52

Odds Ratio

[95% CI]

P-value

SF/APS Clinical Response

1.538 [0.969, 2.442] P=0.068

1.418 [0.894, 2.249] P=0.137

1.596 [1.005, 2.535] P=0.048

2.880 [1.737, 4.774] P< 0.001

4.417 [2.466, 7.909] P< 0.001

3.517 [1.884, 6.565] P< 0.001

SF/APS Clinical Remission

2.084 [1.095, 3.967] P=0.025

1.429 [0.760, 2.684] P=0.268

1.704 [0.889, 3.267] P=0.109

3.696 [1.904, 7.172] P< 0.001

5.368 [2.542, 11.337] P< 0.001

5.091 [2.264, 11.448] P< 0.001

Endoscopic Response

1.066 [0.527, 2.156] P=0.860

0.886 [0.438, 1.793] P=0.736

1.279 [0.613, 2.666] P=0.512

3.592 [1.712, 7.540] P< 0.001

5.765 [2.663, 12.479] P< 0.001

6.314 [2.824, 14.120] P< 0.001

Endoscopic Remission

1.186 [0.503, 2.796] P=0.696

0.810 [0.344, 1.907] P=0.629

1.067 [0.433, 2.625] P=0.888

4.342 [1.732, 10.887] P=0.002

9.227 [3.436, 24.776] P< 0.001

8.036 [2.934, 22.006] P< 0.001

Table: Table. Induction Baseline Characteristics and FORTIFY Week 0 Clinical Outcomes as Predictors of Week 12 Response to Risankizumab Induction and Week 52 Response to Risankizumab Maintenance Dosing

Disclosures:

Jean-Frederic Colombel: AbbVie – Consultant, Grant/Research Support. Amgen – Consultant. Arena – Consultant. BMS – Consultant. Boehringer Ingelheim – Consultant. Celgene Corporation – Consultant. Celltrion – Personal Fees. Eli Lilly – Consultant. Enterome – Personal Fees. Ferring Pharmaceuticals – Consultant. Galmed Research – Consultant. Galxo Smith Kline – Consultant. Genentech – Consultant. Genfit – Stock Options. Imedex – Consultant. Immunic – Consultant. Intestinal Biotech Development – Stock Options. Intestinal Biotech Development – Stock Options. Iterative Scopes – Consultant. Janssen Pharmaceuticals – Advisory Committee/Board Member, Consultant, Grant/Research Support. Kaleido Biosciences – Consultant. MedImmune – Personal Fees. Merck – Consultant. Microba – Consultant. Novartis – Consultant. PBM Capital – Consultant. Pfizer – Consultant. PPM Services – Personal Fees. Protagonist Therapeutics – Consultant. Sanofi – Consultant. Second Genome – Personal Fees. Seres – Personal Fees. Shire – Personal Fees. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support. Theradiag – Personal Fees. TiGenix – Consultant. Vifor – Consultant.

Walter Reinisch: 4SC – Advisory Committee/Board Member, Consultant. Abbott Laboratories – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. AbbVie – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Aesca – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Algernon – Consultant. AM Pharma – Advisory Committee/Board Member, Consultant. Amgen – Advisory Committee/Board Member, Consultant. AMT – Consultant. AOP Orphan – Consultant. Aptalis – Speakers Bureau. Arena Pharmaceuticals – Consultant. Astellas – Advisory Committee/Board Member, Consultant, Speakers Bureau. AstraZeneca – Advisory Committee/Board Member, Consultant. Avaxia – Advisory Committee/Board Member, Consultant. Bioclinica – Consultant. Biogen IDEC – Advisory Committee/Board Member, Consultant. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant. Celgene – Advisory Committee/Board Member, Consultant. Cellerix – Advisory Committee/Board Member, Consultant. Celltrion – Advisory Committee/Board Member, Consultant, Speakers Bureau. Centocor – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. ChemoCentryx – Advisory Committee/Board Member, Consultant. Covance – Consultant. Danone Austria – Advisory Committee/Board Member, Consultant, Speakers Bureau. DSM – Advisory Committee/Board Member, Consultant. Elan – Advisory Committee/Board Member, Consultant, Speakers Bureau. Eli Lilly – Consultant. Ernest & Young – Consultant. Falk Pharma GmbH – Consultant, Grant/Research Support, Speakers Bureau. Ferring – Advisory Committee/Board Member, Consultant, Speakers Bureau. Galapagos – Advisory Committee/Board Member, Consultant. Gatehouse Bio – Consultant. Genentech – Advisory Committee/Board Member, Consultant. Gilead – Consultant. Grünenthal – Advisory Committee/Board Member, Consultant. ICON – Consultant. Immundiagnostik – Grant/Research Support, Speaker. Index Pharma – Consultant. Inova – Advisory Committee/Board Member, Consultant. Intrinsic Imaging – Consultant. Janssen – Advisory Committee/Board Member, Consultant, Grant/Research Support. Johnson & Johnson – Advisory Committee/Board Member, Consultant. Kyowa Hakko Kirin Pharma – Advisory Committee/Board Member, Consultant. Lipid Therapeutics – Advisory Committee/Board Member, Consultant. LivaNova – Consultant. Mallinckrodt – Consultant. Medahead – Consultant. MedImmune – Advisory Committee/Board Member, Consultant. Millenium – Advisory Committee/Board Member, Consultant. Mitsubishi Tanabe Pharma Corporation – Advisory Committee/Board Member, Consultant, Speakers Bureau. MSD – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Nash Pharmaceuticals – Consultant. Nestle – Advisory Committee/Board Member, Consultant. Nippon Kayaku – Consultant. Novartis – Advisory Committee/Board Member, Consultant. Ocera – Advisory Committee/Board Member, Consultant. OMass – Consultant. Otsuka – Advisory Committee/Board Member, Consultant, Speakers Bureau. Parexel – Consultant. PDL – Advisory Committee/Board Member, Consultant, Speakers Bureau. Periconsulting – Consultant. Pfizer – Advisory Committee/Board Member, Consultant. Pharmacosmos – Advisory Committee/Board Member, Consultant, Speakers Bureau. Philip Morris Institute – Consultant. PLS Education – Speakers Bureau. Procter & Gamble – Advisory Committee/Board Member, Consultant. Prometheus – Advisory Committee/Board Member, Consultant. Protagonist – Consultant. Provention – Consultant. Quell Therapeutics – Consultant. Robarts Clinical Trial – Consultant. Roland Berger GmbH – Consultant. Sandoz – Advisory Committee/Board Member, Consultant, Grant/Research Support. Schering-Plough – Advisory Committee/Board Member, Consultant, Speakers Bureau. Second Genome – Advisory Committee/Board Member, Consultant. Seres Therapeutics – Consultant. Setpoint Medical – Advisory Committee/Board Member, Consultant. Shire – Speakers Bureau. Sigmoid – Consultant. Sublimity – Consultant. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Therakos – Advisory Committee/Board Member, Consultant, Speakers Bureau. Theravance – Consultant. TiGenix – Advisory Committee/Board Member, Consultant. UCB – Advisory Committee/Board Member, Consultant. Vifor – Consultant, Speakers Bureau. Yakult – Speakers Bureau. Zealand – Advisory Committee/Board Member, Consultant. Zyngenia – Advisory Committee/Board Member, Consultant.

Stefan Schreiber: AbbVie – Consultant, Personal fees. Arena – Consultant, Personal fees. Biogen – Consultant, Personal fees. Bristol-Myers Squibb – Consultant, Personal fees. Celgene – Consultant, Personal fees. Celltrion – Consultant, Personal fees. Eli Lilly and Company – Consultant, Personal fees. Falk – Consultant, Personal fees. Ferring – Consultant, Personal fees. Fresenius – Consultant, Personal fees. Galapagos/Gilead Sciences – Consultant, Personal fees. IMAB – Consultant, Personal fees. Janssen – Consultant, Personal fees. MSD – Consultant, Personal fees. Mylan – Consultant, Personal fees. Pfizer Inc – Consultant, Personal fees. Protagonist – Consultant, Personal fees. Provention Bio – Consultant, Personal fees. Takeda – Consultant, Personal fees. Theravance – Consultant, Personal fees.

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.

Ken Sugimoto: AbbVie – Consultant, Joint research agreement. Asahi Kasei Medical Co. – Consultant, Grant/Research Support. Astellas BioPharma – Joint research agreement. Bristol-Myers Squibb(BMS) – Joint research agreement. Chugai Pharmaceutical – Grant/Research Support. Daiichi Sankyo – Consultant. EA Pharma – Consultant, Grant/Research Support. Eli Lilly – Consultant, Grant/Research Support. Janssen – Consultant. JIMRO Co. – Consultant. Kissei Pharmaceutical – Grant/Research Support. Kyorin – Consultant, Grant/Research Support. Mitsubishi Tanabe Pharma Corporation – Consultant, Grant/Research Support, Joint research agreement. Mochida Pharmaceutical – Consultant, Joint research agreement. Nippon Kayaku – Consultant, Grant/Research Support. Otsuka Pharmaceutical – Consultant, Grant/Research Support. Pfizer – Consultant. Sanofi – Grant/Research Support. Taiho – Consultant, Grant/Research Support. Takeda – Consultant. Tsumura & Co., – Grant/Research Support. Zeria Pharmaceutical – Consultant.

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.

Naomi Martin: AbbVie – Employee, Stock Options.

Kristina Kligys: AbbVie – Employee, Stock Options.

Valerie Pivorunas: AbbVie – Employee, Stock Options.

Alexandra Song: AbbVie – Employee, Stock Options.

Javier Zambrano: AbbVie – Employee, Stock Options.

Yafei Zhang: AbbVie – Employee, Stock Options.

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.