P1640 - Efficacy of Upadacitinib Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis by Biologic Inadequate Responder Status: Results From Two Randomized Phase 3 Studies

Monday, October 25, 2021

10:30 AM – 4:15 PM PT

Location: Shoreline Exhibit Hall

Has Audio

Presenting Author(s)

David T. Rubin, MD, FACG

University of Chicago Medicine, Inflammatory Bowel Disease Center
Chicago, IL, United States

Severine Vermeire, MD, PhD¹, Satoshi Tanida, MD², Renwei Hu, MD³, Remo Panaccione, MD, FRCP⁴, Xavier Hébuterne, MD⁵, David T. Rubin, MD, FACG⁶, Dapo Ilo, MD⁷, Wen Zhou, PhD⁸, Michael Weinreich, PhD⁸, Qing Zhou, MD⁸, Silvio Danese, MD, PhD⁹
¹University Hospitals Leuven, Leuven, Brussels Hoofdstedelijk Gewest, Belgium; ²Naogoya City University Hospital, Nagoya, Aichi, Japan; ³West China Hospital, Chengdu, Sichuan, China; ⁴Inflammatory Bowel Disease Clinic, Gastrointestinal Research, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; ⁵CHU de Nice, Université Côte d’Azur, Nice, Lorraine, France; ⁶University of Chicago Medicine, Inflammatory Bowel Disease Center, Chicago, IL; ⁷AbbVie, Inc., North Chicago, IL; ⁸AbbVie Inc., North Chicago, IL; ⁹Inflammatory Bowel Diseases Center, Humanitas Clinical and Research Center IRCCS and Hunimed, Milan, Lombardia, Italy

Introduction: Upadacitinib (UPA), an oral JAK inhibitor, showed significantly greater efficacy vs placebo (PBO) in induction treatment of patients (pts) with moderately-to-severely active ulcerative colitis (UC) in two phase 3 induction trials, U-ACHIEVE and U-ACCOMPLISH. We evaluated efficacy of UPA in pts who had an inadequate response (IR), loss of response, or intolerance to biologic therapies (Bio-IR) or were non-Bio-IR.

Methods: U-ACHIEVE and U-ACCOMPLISH, multicentre, double-blind, placebo (PBO)-controlled trials, randomized pts with moderately to severely active UC to UPA 45 mg QD or PBO for 8 weeks (wks). Randomization was stratified by status of previous biologic failure, ie an inadequate response (IR), loss of response, or intolerance to biologic therapies (Bio-IR or bio-failure) vs non-Bio-IR (non-bio-IR or non-bio-failure), baseline corticosteroid use (yes or no), and baseline adapted Mayo score (≤7 or >7). Efficacy endpoints included primary endpoint of clinical remission (adapted Mayo score) at Wk 8 and ranked secondary endpoints of clinical response (partial adapted Mayo score at Wk 2 and adapted Mayo score at Wk 8), endoscopic improvement (Mayo endoscopic subscore 0 or 1), endoscopic remission (Mayo endoscopic subscore 0) and histologic-endoscopic mucosal improvement at Wk 8 (HEMI; endoscopic subscore ≤1 and Geboes score ≤3.1). Results using non-responder imputation incorporating multiple imputation for missing data due to COVID-19 are reported.

Results: In both studies, approximately half the pts were Bio-IR (Table). In both Bio-IR and non-Bio-IR pts, significantly higher proportion of pts receiving UPA achieved primary endpoint of clinical remission versus PBO; the magnitude of clinical remission at Wk 8 was greater in non-Bio-IR pts (UPA, 35% vs PBO, 9%; treatment difference [95% CI]: 26.0% [16.0, 36.1]) versus Bio-IR (UPA, 18% vs PBO, 0%; 17.5% [11.4, 23.6]) in U-ACHIEVE and non-Bio-IR (UPA, 38% vs PBO, 6%; 31.6% [22.8, 40.5]) versus Bio-IR (UPA, 30% vs PBO, 2%; 27.1% [19.6, 34.7]; Table) in U-ACCOMPLISH. Results were generally similar for ranked secondary endpoints (Table). UPA 45 mg QD was well-tolerated and no new safety signals were observed.

Discussion: UPA 45 mg QD is an effective induction treatment for pts with moderately to severely active UC. A significantly higher proportion of pts in both Bio-IR and non-Bio-IR groups receiving UPA achieved primary and secondary endpoints versus PBO. The magnitude of difference was greater among pts who were non-Bio-IR versus Bio-IR.

	U-ACHIEVE Bio-IR		U-ACHIEVE Non-Bio-IR		U-ACCOMPLISH Bio-IR		U-ACCOMPLISH Non-Bio-IR
n (%) [95% CI]	PBO (n=78)	UPA (n=168)	PBO (n=76)	UPA (n=151)	PBO (n=89)	UPA (n=173)	PBO (n=85)	UPA (n=168)
Clinical remission at week 8	0 [0.0, 2.3]	30 (18%) [12.1, 23.8]	7 (9%) [2.7, 15.7]	53 (35%) [27.6, 42.9]	2 (2%) [0.0, 5.7]	51 (30%) [22.8, 36.4]	5 (6%) [0.9, 10.9]	63 (38%) [30.2, 44.8]
Clinical response at week 2	13 (17%) [8.4, 24.9]	91 (54%) 46.6, 61.7]	29 (38%) [27.2, 49.1]	101 (67%) [59.2, 74.3]	18 (20%) [11.9, 28.6]	108 (62%) [55.2, 69.6]	27 (32%) [21.9, 41.7]	108 (64%) [57.0, 71.5]
Clinical response at week 8	10 (13%) [5.4, 20.2]	108 (64%) [57.1, 71.6]	32 (42%) [31.0, 53.2]	124 (82%) [75.6, 88.0]	17 (19%) [11.0, 27.5]	120 (69%) [62.5, 76.2]	27 (32%) [21.9, 41.7]	134 (80%) [73.7, 85.8]
Endoscopic improvement at week 8	1 (2%) [0.0, 4.8]	45 (27%) [20.2, 33.7]	10 (13%) [5.6, 20.8]	71 (47%) [38.7, 54.8]	4 (5%) [0.2, 9.4]	64 (37%) [29.9, 44.3]	10 (12%) [5.0, 18.9]	86 (51%) [43.6, 58.7]
Endoscopic remission at week 8	0 [0.0, 0.0]	15 (9%) [4.6, 13.3]	2 (3%) [0.0, 6.2]	29 (19%) [12.7, 25.4]	1 (1%) [0.0, 3.4]	22 (13%) [7.8, 17.7]	2 (2%) [0.0, 5.6]	40 (24%) [17.4, 30.3]
HEMI at week 8	1 (1%) [0.0, 4.1]	38 (23%) [16.3, 29.1]	9 (12%) [4.6, 19.1]	57 (38%) [30.2, 45.9]	4 (5%) [0.2, 8.9]	53 (31%) [23.8, 37.6]	6 (7%) [1.6, 12.7]	72 (43%) [35.4, 50.3]

Table: Table. Efficacy endpoints in Bio-IR and non-Bio-IR patients based on randomized treatment
IR: inadequate response; Bio-IR: inadequate response, loss of response, or intolerance to biologic therapies.
Clinical response at week 2 per partial adapted Mayo score (stool frequency subscore + rectal bleeding subscore).
Clinical response at week 8 per adapted Mayo score (stool frequency subscore + rectal bleeding subscore + endoscopic subscore).

Disclosures:
Severine Vermeire: AbbVie – Consultant, Grant/Research Support. Arena Pharmaceuticals, Avaxia, Boehringer Ingelheim – Consultant, Speaker's Bureau. Celgene, Dr Falk Pharma, Ferring, – Consultant, Speaker's Bureau. Galapagos, Genentech-Roche, Gilead, Hospira, – Consultant, Speaker's Bureau. J&J – Grant/Research Support. Janssen, Mundipharma, MSD – Consultant, Speaker's Bureau. Pfizer – Consultant, Grant/Research Support. Prodigest, Progenity, Prometheus, Robarts Clinical Trials, – Consultant, Speaker's Bureau. Second Genome, Shire, – Consultant, Speaker's Bureau. Takeda – Consultant, Grant/Research Support. Theravance, and Tillots Pharma AG. – Consultant, Speaker's Bureau.
Satoshi Tanida: AbbVie – Grant/Research Support. EA Pharma Co., Ltd – Grant/Research Support.
Renwei Hu indicated no relevant financial relationships.
Remo Panaccione: Abbott, Alimentiv (formerly Robarts), – Consultant. AbbVie – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speaker's Bureau. Amgen – Advisory Committee/Board Member, Consultant. Arena Pharmaceuticals – Advisory Committee/Board Member, Consultant, Speaker's Bureau. AstraZeneca, Boehringer Ingelheim – Consultant. Bristol-Myers Squibb – Advisory Committee/Board Member, Consultant. Celgene – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Celltrion – Advisory Committee/Board Member, Consultant. Cosmos Pharmaceuticals, Eisai, Elan, – Consultant. Eli Lilly – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Ferring – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speaker's Bureau. Galapagos – Advisory Committee/Board Member, Consultant. Genentech, – Advisory Committee/Board Member, Consultant. Gilead Sciences, – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Glaxo-Smith Kline – Consultant, Speaker's Bureau. Janssen – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speaker's Bureau. Merck & Co – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Mylan – Advisory Committee/Board Member, Consultant. Oppilan Pandion, Oppilan Pandion – Advisory Committee/Board Member, Consultant. Pfizer – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speaker's Bureau. Pharma, UCB, Schering-Plough – Consultant. Progenity, Protagonist Therapeutics, – Consultant. Roche – Advisory Committee/Board Member, Speaker's Bureau. Sandoz, Shire, – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Satisfai Health – Consultant. Sublimity Therapeutics – Advisory Committee/Board Member, Consultant. Takeda Pharmaceuticals – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speaker's Bureau. Theravance Biopharma – Advisory Committee/Board Member, Consultant.
Xavier Hébuterne: AbbVie – Advisory Committee/Board Member, Grant/Research Support, Other Financial or Material Support, lectures and educational activities. Abivax, Alphasigma, – Grant/Research Support. Amgen, Baxter, Fresenius Kabi, Janssen – Other Financial or Material Support, lectures and educational activities. Arena Pharmaceuticals – Advisory Committee/Board Member, Grant/Research Support. Celgene, Eli Lilly, Enterome, – Grant/Research Support. Gilead, Janssen, – Advisory Committee/Board Member, Grant/Research Support. InDex Pharmaceuticals – Grant/Research Support. MSD, Mylan, Nutricia, Pfizer, Tillots, – Other Financial or Material Support, lectures and educational activities. Pfizer, – Advisory Committee/Board Member, Grant/Research Support. Roche – Advisory Committee/Board Member, Grant/Research Support. Salix, Sangamo, – Grant/Research Support. Takeda – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, lectures and educational activities. Theravance, – Grant/Research Support.
David Rubin: Abbvie, Altrubio, Allergan Inc., Arena Pharmaceuticals – Consultant. Bellatrix Pharmaceuticals, Boehringer Ingelheim Ltd., – Consultant. Bristol-Myers Squibb, Celgene Corp/Syneos, GalenPharma/Atlantica, – Consultant. Genentech/Roche, Gilead Sciences, InDex Pharmaceuticals, – Consultant. Ironwood Pharmaceuticals, Iterative Scopes, – Consultant. Janssen Pharmaceuticals, Lilly, Materia Prima, Pfizer, – Consultant. Prometheus Biosciences, Reistone, Techlab Inc – Consultant. Takeda – Consultant, Grant/Research Support.
Dapo Ilo: AbbVie – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Wen Zhou: AbbVie – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Michael Weinreich: AbbVie – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Qing Zhou: AbbVie – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Silvio Danese: Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Ferring, Genentech, Grunenthal, Johnson and Johnson – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Millenium Takeda, MSD, Nikkiso Europe GmbH – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Novo Nordisk, Nycomed, Pfizer, – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Pharmacosmos, UCB Pharma and Vifor. – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Schering-Plough, AbbVie, Actelion – Advisory Committee/Board Member, Consultant, Speaker's Bureau.

Severine Vermeire, MD, PhD¹, Satoshi Tanida, MD², Renwei Hu, MD³, Remo Panaccione, MD, FRCP⁴, Xavier Hébuterne, MD⁵, David T. Rubin, MD, FACG⁶, Dapo Ilo, MD⁷, Wen Zhou, PhD⁸, Michael Weinreich, PhD⁸, Qing Zhou, MD⁸, Silvio Danese, MD, PhD⁹. P1640 - Efficacy of Upadacitinib Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis by Biologic Inadequate Responder Status: Results From Two Randomized Phase 3 Studies, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.