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Poster Session D - Tuesday Morning

D0380 - Impact of Inflammatory Burden on Efficacy of Upadacitinib Maintenance Therapy in Ulcerative Colitis: Results From the Phase 3 U-ACHIEVE Study

Tuesday, October 25, 2022

10:00 AM – 12:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

Brian G. Feagan, MD

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

Brian G. Feagan, MD¹, Jean-Frederic Colombel, MD², Joana Torres, MD, PhD³, Toshimitsu Fujii, MD⁴, Wen Zhou, MD, PhD⁵, Xuan Yao, PhD⁶, Yuri Sanchez-Gonzalez, PhD⁶, Dapo Ilo, MBBS, MRCS, MSc⁶, Xavier Roblin, MD⁷
¹Alimentiv, Inc.; Western University, London, ON, Canada; ²Icahn School of Medicine at Mount Sinai, New York, NY; ³Hospital Beatriz Ângelo, Loures, Portugal and Hospital da Luz, Lisbon, Lisboa, Portugal; ⁴Tokyo Medical and Dental University, Tokyo, Tokyo, Japan; ⁵AbbVie Inc., North Chicago, IL; ⁶AbbVie, Inc., North Chicago, IL; ⁷University of Lyon, Saint-Etienne, Rhone-Alpes, France

Introduction: Upadacitinib (UPA) has demonstrated superior efficacy to placebo (PBO) and a favorable safety profile in patients with moderately to severely active ulcerative colitis (UC) in trial U-ACHIEVE Maintenance, in which two maintenance doses of UPA (30mg and 15mg once daily [QD]) were evaluated.^1–3 However, data are limited on the impact of inflammatory burden on the efficacy of the two maintenance doses.

Methods: The primary efficacy analysis of U-ACHIEVE Maintenance included the first 451 patients who achieved a clinical response (per Adapted Mayo score) after 8 weeks of UPA 45mg QD treatment in the induction trials. The primary endpoint was clinical remission per Adapted Mayo score at Week 52 and a key secondary endpoint was endoscopic improvement at Week 52. This post hoc analysis evaluated the efficacy, based on these endpoints, of UPA 30mg vs UPA 15mg maintenance therapy in patients in U-ACHIEVE Maintenance stratified by three measures of inflammatory burden: baseline Full Mayo score >9 vs ≤9, presence of pancolitis (yes vs no), and presence of ≥1 extraintestinal manifestation (yes vs no).

Results: Overall, 451 patients (PBO: n=149, UPA 15mg: n=148, and UPA 30mg: n=154) were included in the intent-to-treat maintenance population. Both UPA 30mg and UPA 15mg demonstrated favorable efficacy compared with PBO, regardless of the inflammatory burden (Table). However, the differences in proportions of responders who achieved clinical remission at Week 52 and who received UPA 30mg vs UPA 15mg were greater in patients with a high inflammatory burden (difference range: 12.0–22.0%) than those patients without a high inflammatory burden (difference range: 1.4–6.2%; Table). Similar results were seen for proportions of patients who achieved endoscopic improvement at Week 52 (high inflammatory burden [difference range: 12.0–26.1%] relative to those without high inflammatory burden [difference range: 0.2–14.1%]).

Discussion: Both UPA maintenance doses were efficacious compared with PBO, regardless of inflammatory burden, in the achievement of clinical remission and endoscopic improvement. Although results should be interpreted with respect to the small sample size in some subgroups and the post hoc nature of the analysis, these data suggest that patients with a high inflammatory burden of UC may have a relatively greater benefit from UPA 30mg than UPA 15mg, compared with those without high inflammatory burden.

PBO,

n/N (%)

(N=149)

UPA 15 mg QD,
n/N (%)

(N=148)

UPA 30 mg QD,
n/N (%)

(N=154)

Difference between UPA 30 mg
vs UPA 15 mg^a, %

Primary endpoint: Clinical remission^b at Week 52 per Adapted Mayo Score

BL Full Mayo score ≤9

BL Full Mayo score >9

7/74 (9.5)

11/75 (14.8)

40/75 (53.1)

23/73 (31.2)

40/73 (54.5)

40/79 (50.4)

1.4

19.2

Pancolitis at BL, no

Pancolitis at BL, yes

13/79 (16.5)

5/70 (7.1)

31/66 (46.6)

32/82 (38.8)

36/68 (52.8)

44/86 (50.8)

6.2

12.0

EIM at BL, no

EIM at BL, yes

13/112 (11.6)

5/37 (13.7)

50/112 (44.3)

13/36 (36.1)

56/113 (49.4)

24/41 (58.1)

5.1

22.0

Key secondary endpoint: Endoscopic improvement^c at Week 52

BL Full Mayo score ≤9

BL Full Mayo score >9

8/74 (10.8)

14/75 (18.1)

45/75 (60.4)

27/73 (36.7)

44/73 (60.6)

50/79 (62.8)

0.2

26.1

Pancolitis at BL, no

Pancolitis at BL, yes

16/79 (20.3)

6/70 (8.0)

33/66 (49.6)

39/82 (47.9)

43/68 (63.7)

52/86 (59.9)

14.1

12.0

EIM at BL, no

EIM at BL, yes

15/112 (13.7)

6/37 (16.9)

57/112 (50.9)

15/36 (41.7)

68/113 (60.2)

27/41 (65.4)

9.3

23.7

Data are from the ITT population, defined as the first 450 randomized and treated patients with 8-week UPA 45 mg QD induction treatment who were enrolled in Cohort 1 under the protocol for the 52-week maintenance treatment period. The actual number of patients in the analysis was 451 due to the same enrollment date of the 450^th and 451^st patients. Non-responder imputation incorporating multiple imputations was performed to handle missing data due to COVID-19 incidence.

^aNot part of the predefined statistical analyses.

^bAdapted Mayo score ≤2, with stool frequency subscore ≤1 (and not greater than induction baseline), rectal bleeding subscore of 0, and endoscopic subscore ≤1.

^cEndoscopic subscore ≤1.
BL, baseline; EIM, extraintestinal manifestation; ITT, intent-to-treat; PBO, placebo; QD, once daily; UPA, upadacitinib.

Disclosures:

Brian Feagan: AbbVie – Consultant, Member of the scientific advisory board, Speakers Bureau. AbolerIS – Consultant. AgomAB Therapeutics – Consultant. Alimentiv Inc – Employee. 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.

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.

Joana Torres: AbbVie – Advisory Committee/Board Member, Grant/Research Support, Speaker fees. Arena – Advisory Committee/Board Member. Galapagos – Advisory Committee/Board Member, Lecture fees. Janssen Pharmaceuticals – Advisory Committee/Board Member, Grant/Research Support, Lecture fees. Pfizer Inc – Advisory Committee/Board Member.

Toshimitsu Fujii: AbbVie – Grant/Research Support, Speakers Bureau. Ajinomoto – Speakers Bureau. Alfresa – Grant/Research Support. Boehringer-Ingelheim – Grant/Research Support, Speakers Bureau. Bristol-Myers Squibb(BMS) – Grant/Research Support, Speakers Bureau. Celgene – Grant/Research Support. Daiichi Sankyo – Speakers Bureau. EA Pharma – Grant/Research Support, Speakers Bureau. Eisai – Grant/Research Support. Eli Lilly – Grant/Research Support. Gilead – Grant/Research Support. Janssen – Grant/Research Support, Speakers Bureau. Kissei – Grant/Research Support, Speakers Bureau. Kyorin – Speakers Bureau. Kyowa Hakko Kirin – Speakers Bureau. Mebix – Grant/Research Support. Mitsubishi-Tanabe – Speakers Bureau. Mochida – Speakers Bureau. Nichiiko – Speakers Bureau. Nippon Kayaku – Speakers Bureau. Taiho – Speakers Bureau. Takeda – Grant/Research Support, Speakers Bureau. Zeria – Speakers Bureau.

Wen Zhou: AbbVie – Employee, Stock Options.

Xuan Yao: AbbVie – Employee, Stock Options.

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

Dapo Ilo: AbbVie – Employee, Stock Options.

Xavier Roblin indicated no relevant financial relationships.

Brian G. Feagan, MD¹, Jean-Frederic Colombel, MD², Joana Torres, MD, PhD³, Toshimitsu Fujii, MD⁴, Wen Zhou, MD, PhD⁵, Xuan Yao, PhD⁶, Yuri Sanchez-Gonzalez, PhD⁶, Dapo Ilo, MBBS, MRCS, MSc⁶, Xavier Roblin, MD⁷. D0380 - Impact of Inflammatory Burden on Efficacy of Upadacitinib Maintenance Therapy in Ulcerative Colitis: Results From the Phase 3 U-ACHIEVE Study, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.