1 - Benefits of High versus Low Dose Upadacitinib as Maintenance Treatment in Ulcerative Colitis Patients Who Were Responders to 8-week Induction with Upadacitinib: Results From the U-ACHIEVE Phase 3 Maintenance Trial

Monday, October 24, 2022

8:00 AM – 8:12 AM ET

Location: Hall C2

Presenting Author(s)

Brian G. Feagan, MD

Alimentiv, Inc.; Western University
London, ON, Canada

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Award: Outstanding Research Award in the IBD Category

Brian G. Feagan, MD¹, Gareth Parkes, DO², Pascal Juillerat, MD³, Krisztina Gecse, MD⁴, Xuan Yao, PhD⁵, Wen Zhou, MD, PhD⁶, Huiwen Deng, PharmD⁷, Dapo Ilo, MBBS, MRCS, MSc⁵, Yuri Sanchez-Gonzalez, PhD⁵, Peter D. Higgins, MD, PhD, MSc⁸
¹Alimentiv, Inc.; Western University, London, ON, Canada; ²Barts Health NHS Trust and London School of Medicine and Dentistry, London, England, United Kingdom; ³Inselspital Bern and Bern University, Bern, Bern, Switzerland; ⁴Academic Medical Center, Amsterdam, Zuid-Holland, Netherlands; ⁵AbbVie, Inc., North Chicago, IL; ⁶AbbVie Inc., North Chicago, IL; ⁷AbbVie, Inc. and University of Illinois at Chicago, Chicago, IL; ⁸University of Michigan, Ann Arbor, MI

Introduction: Evaluate the benefits of upadacitinib (UPA) 30mg (UPA30) vs 15mg (UPA15) once daily (QD) as maintenance treatment in patients (pts) with active ulcerative colitis (UC).

Methods: This post-hoc analysis included pts with clinical response after 8 wks of induction (16-wk induction responders were excluded) with UPA 45mg QD who were enrolled in U-ACHIEVE maintenance trial and re-randomized 1:1:1 to UPA15, UPA30, or placebo (PBO) QD for 52 wks. Clinical remission per Partial Adapted Mayo score were evaluated in subgroups of pts with mild (Adapted Mayo score < 5), moderate (Adapted Mayo score 5 to ≤7), or severe (Adapted Mayo score >7) UC at wks 0 and 52 of maintenance. For each UPA dose, area under the curve (AUC) analysis on proportion of pts in clinical remission per Partial Adapted Mayo score at wks 0, 4, 8, 12, 20, 28, 36, 44 and 52 of maintenance was used to calculate the number of wks pts were in clinical remission. To assess these benefits in the non-elder population, analysis was replicated for UPA doses in pts < 65 years.

Results: Data from 451 pts (UPA15, n=149; UPA30, n=148; PBO, n=154) were analyzed. At Wk 0 of maintenance, at least 91% of pts had mild disease and no pts had severe disease across treatment groups (Table). At the end of 52-wks maintenance, 19.7% more UPA30 pts were in lesser disease severity (10.5% and 9.2% more pts with mild and moderate disease, respectively) vs UPA15. Based on AUC analysis, PBO pts, UPA15 and UPA30 pts were in clinical remission for 15.8 (95% CI: 12.2, 19.5), 30.5 (95% CI: 26.4, 34.6), and 34.4 (95% CI: 30.5, 38.3) wks, respectively. UPA30 pts were in clinical remission for an additional 3.8 wks (26.9 days) over a year of maintenance vs UPA15. In pts < 65 years old (n=411), 26% more UPA30 pts were in lesser disease severity (14% and 12% more pts with mild and moderate disease, respectively) vs UPA15 and were in clinical remission for an additional 4.2 wks (29.3 days) over a year of maintenance vs UPA15.

Discussion: After 52-wks of maintenance treatment with UPA 30mg QD, pts had less severe disease and were in clinical remission for approximately 1 additional month/year vs pts treated with UPA 15mg QD indicating clinical benefit of high dose UPA as maintenance treatment in UC.

Patients with mild, moderate, and severe UC at Weeks 0 and 52 and weeks in clinical remission
		Week 0			Week 52^a			Weeks in Clinical Remission^b
n (%)	N	Mild	Moderate	Severe	Mild	Moderate	Severe	Mean (95% CI)
PBO	149	137 (92.0)	12 (8.1)	0	34 (22.8)	70 (47.0)	45 (30.2)	15.8 (12.2, 19.5)
UPA 15 mg	148	136 (91.9)	11 (7.4)	0	94 (63.5)	25 (16.9)	28 (18.9)	30.5 (26.4, 34.6)
UPA 30 mg	154	141 (91.6)	13 (8.4)	0	114 (74.0)	24 (15.6)	15 (9.7)	34.4 (30.5, 38.3)
^aPatients with Adapted Mayo scores collected at or after initiation of UC-related rescue medications through the end of the maintenance study or who prematurely discontinued from the study were assumed to have Week 52 Adapted Mayo score return to baseline. Patients with missing data for reasons other than UC-related rescue medications or premature discontinuation were handled by last observation carried forward. Disease severity was defined by Adapted Mayo score: mild (Adapted Mayo < 5), moderate (Adapted Mayo 5 to ≤7), and severe (Adapted Mayo >7). ^bClinical remission was defined as Partial Adapted Mayo score ≤2 with no subscore >1.

Table: Patients with mild, moderate, and severe UC at Weeks 0 and 52 and weeks in clinical remission

Disclosures:

Brian Feagan: AbbVie – Consultant, Member of the scientific advisory board, Speakers Bureau. AbolerIS – Consultant. AgomAB Therapeutics – Consultant. Alimentiv Inc – Consultant. Allianthera – Consultant. Amgen – Consultant, Member of the scientific advisory board. AnaptysBio – Consultant. Applied Molecular Transport Inc. – Consultant. Arena Pharma – Consultant. Avir – Consultant. Azora Therapeutics – Consultant. BioJamp – Consultant. Biopharma – Consultant. Biora Therapeutics – Consultant. Boehringer-Ingelheim – Consultant, Member of scientific advisory board. Boston Pharma – Consultant. Boxer – Consultant. Celgene/BMS – Consultant, Member of scientific advisory board. Connect BioPharma – Consultant. Cytoki – Consultant. Disc Medicine – Consultant. Duality – Consultant. EcoR1 Capital – Consultant, Member of the scientific advisory board. Eli Lilly and Company – Consultant. Equillium – Consultant. Ermium – Consultant. Everest Clinical Research Corp. – Consultant. Ferring – Consultant. First Wave – Consultant. Galapagos – Consultant. Galen Atlantica – Consultant. Genentech/Roche – Consultant, Member of scientific advisory board. Gilead – Consultant. Glenmark – Consultant. Gossamer Pharma – Consultant, Stock Shareholder. GSK – Consultant, Member of the scientific advisory board. Hoffmann-LaRoche – Consultant. Hot Spot Therapeutics – Consultant. Imhotex – Consultant. ImmunExt – Consultant. Immunic Therapeutics – Consultant. Index Pharma – Consultant, Member of the scientific advisory board. Intact Therapeutics – Consultant. JAKAcademy – Consultant. Janssen – Consultant, Member of scientific advisory board, 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 – Consultant, Member of the scientific advisory board. Mylan – Consultant. Novartis – Member of the scientific advisory board. OM Pharma – Consultant. Origo BioPharma – Consultant, Member of scientific advisory board. Orphagen – Consultant. Otsuka – Consultant. Pandion Therapeutics – Consultant. Pfizer – Consultant, Member of the scientific advisory board. Play to Know AG – Consultant. Progenity – Consultant, Member of the scientific advisory board. Prometheus – Member of scientific advisory board. Prometheus Therapeutics and Diagnostics – Consultant. Protagonist – Consultant. PTM Therapeutics – Consultant. Q32 Bio – Consultant. Rebiotix – Consultant. RedHill – Consultant. REDX – Consultant. Roche – Consultant. Sandoz – Consultant. Sanofi – Consultant. Seres Therapeutics – Consultant. Silverback Therapeutics – Consultant. Surrozen Inc. – Consultant. Takeda – Consultant, Member of the scientific advisory board, Speakers Bureau. Teva – Consultant, Member of the scientific advisory board. Thelium – Consultant. Theravance – Consultant. Tigenix – Consultant. Tillotts Pharma – Consultant, Member of the scientific advisory board. UCB Pharma – Consultant. VHsquared Ltd. – Consultant. Viatris – Consultant. Western University – Employee. Ysios – Consultant. Ysopia – Consultant. Zealand Pharma – Consultant.

Gareth Parkes: AbbVie – Personal payments/honoraria/speaker fees, Speakers Bureau. Allergan – Personal payments/honoraria/speaker fees, Speakers Bureau. Ampersand Health – Director and Shareholder. Ferring – Personal payments/honoraria/speaker fees, travel grants or fellowships, Speakers Bureau. Janssen – Personal payments/honoraria/speaker fees, travel grants or fellowships, Speakers Bureau. Napp – Speakers Bureau. Takeda – Personal payments/honoraria/speaker fees, travel grants or fellowships, Speakers Bureau. Tillots Pharma – Speakers Bureau.

Pascal Juillerat: AbbVie – Consultant, Speakers Bureau. Amgen – Consultant, Speakers Bureau. Arena – Consultant, Speakers Bureau. Bristol-Myers Squibb(BMS) – Consultant, Speakers Bureau. Eli Lilly – Consultant, Speakers Bureau. Ferring – Consultant, Speakers Bureau. Gilead – Consultant, Speakers Bureau. Janssen – Consultant, Speakers Bureau. MSD – Consultant, Speakers Bureau. Pfizer – Consultant, Speakers Bureau. Pierre Fabre – Consultant, Speakers Bureau. Roche – Consultant, Speakers Bureau. Sandoz – Consultant, Speakers Bureau. Takeda – Consultant, Speakers Bureau. Tillots Pharma – Consultant, Speakers Bureau. UCB – Consultant, Speakers Bureau. Vifor Pharma – Grant/Research Support.

Krisztina Gecse: AbbVie – Consultant. Arena Pharmaceuticals – Consultant. Ferring – Speakers Bureau. Gilead – Consultant. Immunic Therapeutics – Consultant. Janssen – Consultant, Speakers Bureau. Novartis – Consultant, Speakers Bureau. Samsung Bioepis – Consultant, Speakers Bureau. Takeda – Consultant, Speakers Bureau. Tillots Pharma – Speakers Bureau.

Xuan Yao: AbbVie – Employee, Stock Options.

Wen Zhou: AbbVie – Employee, Stock Options.

Huiwen Deng: AbbVie – Employee. University of Illinois at Chicago – Employee, Research fellow and student.

Dapo Ilo: AbbVie – Employee, Stock Options.

Yuri Sanchez-Gonzalez: AbbVie – Employee, Stock Options.

Peter Higgins: AbbVie – Consultant. Amgen – Consultant. Eli Lilly – Consultant. Gastrointestinal Health Foundation – Consultant. Genentech – Consultant. Imedex – Consultant. JBR Pharma – Consultant. Lycera – Consultant. National Institutes of Health – Grant/Research Support. Pfizer – Consultant. Takeda – Consultant, Grant/Research Support. The Crohn’s & Colitis Foundation – Grant/Research Support. Vindico Medical Education – Consultant.

Brian G. Feagan, MD¹, Gareth Parkes, DO², Pascal Juillerat, MD³, Krisztina Gecse, MD⁴, Xuan Yao, PhD⁵, Wen Zhou, MD, PhD⁶, Huiwen Deng, PharmD⁷, Dapo Ilo, MBBS, MRCS, MSc⁵, Yuri Sanchez-Gonzalez, PhD⁵, Peter D. Higgins, MD, PhD, MSc⁸, 1, Benefits of High versus Low Dose Upadacitinib as Maintenance Treatment in Ulcerative Colitis Patients Who Were Responders to 8-week Induction with Upadacitinib: Results From the U-ACHIEVE Phase 3 Maintenance Trial, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.