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Oral Paper Presentation

Annual Scientific Meeting

Session: Plenary Session 4A - Colon / IBD

61 - Efficacy and Safety of Upadacitinib in Patients With Moderate to Severe Active Ulcerative Colitis Receiving 16 Weeks Extended Induction Treatment Followed by 52 Weeks Maintenance Treatment in U-ACHIEVE/U-ACCOMPLISH Trials

Wednesday, October 26, 2022

9:30 AM – 9:40 AM ET

Location: Hall C2

Presenting Author(s)

Edward V. Loftus, Jr., MD, FACG

Professor of Medicine
Division of Gastroenterology and Hepatology, Mayo Clinic
Rochester, MN

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Remo Panaccione, MD¹, Silvio Danese, MD, PhD², Wen Zhou, MD, PhD³, Justin Klaff, MD⁴, Dapo Ilo, MBBS, MRCS, MSc⁴, Xuan Yao, PhD⁴, Gweneth Levy, MD⁴, Peter D. Higgins, MD, PhD, MSc⁵, Edward V. Loftus, MD, FACG⁶, Séverine Vermeire, MD, PhD⁷
¹University of Calgary, Calgary, AB, Canada; ²IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Molise, Italy; ³AbbVie Inc., North Chicago, IL; ⁴AbbVie, Inc., North Chicago, IL; ⁵University of Michigan, Ann Arbor, MI; ⁶Mayo Clinic College of Medicine and Science, Rochester, MN; ⁷University Hospitals Leuven, Leuven, Brussels Hoofdstedelijk Gewest, Belgium

Introduction: This analysis evaluated efficacy and safety of UPA after extended induction treatment(UPA 45mg QD for 16 wks) and subsequent maintenance treatment(UPA 15mg QD or UPA 30mg QD for 52 wks).

Methods: Patients who did not achieve clinical response(Adapted Mayo score decrease ≥2 points and ≥30% from baseline, plus ≥1 point decrease in rectal bleeding score [RBS] or absolute RBS ≤1) following initial 8 weeks (wks) UPA 45mg once daily (QD) treatment in induction trials were eligible to receive additional 8‑wk, open-label extended treatment with UPA 45mg QD. Patients with clinical response following completion of the extended induction(Wk 16) were re-randomized 1:1 to UPA 15mg QD or UPA 30mg QD in U‑ACHIEVE Maintenance trial(NCT02819635).

Results: Of patients who received UPA 45mg QD in the induction trials, 125 did not achieve clinical response at 8 wks and received further 8 wks induction treatment. At Wk 16, 73/125(58.4%) subsequently responded and were re‑randomized to maintenance UPA 15mg QD or UPA 30mg QD. Among 16-wk responders who entered the maintenance trial, a greater proportion of patients who received UPA 30mg QD vs UPA 15mg QD achieved the primary endpoint of clinical remission at 52 wks(43.6% vs 26.5%, respectively), and secondary endpoints of clinical response(78.1% vs 49.1%, respectively) and endoscopic improvement(51.3% vs 34.3%, respectively) at 52 wks(Table). A similar pattern was seen across clinical, endoscopic, and histologic endpoints(Table). At Wk 52, the proportions of patients with serious adverse events(AEs) were 2.9% with UPA 15mg QD and 10.0% with UPA 30mg QD. Selected AEs of special interest with UPA 15mg QD and UPA 30mg QD included serious infection(2.9% vs 5.0% of patients, respectively), herpes zoster(0% vs 5.0%, respectively), adjudicated major adverse cardiovascular events(0% vs 2.5%, respectively), and non-melanoma skin cancer(NMSC; 0% vs 2.5%, respectively). No adjudicated venous thromboembolic events or cases of malignancy excluding NMSC were reported with UPA doses.

Discussion: Extended induction treatment for further 8 wks with UPA 45mg QD induced response in over half of patients with UC who did not achieve a response after 8 wks. The benefit of maintenance therapy in delayed responders was shown with both UPA doses, though UPA 30mg QD provided greater benefit than UPA 15mg QD. UPA was well tolerated with no new safety signals and selected AEs of special interest were reported infrequently with both maintenance doses.

Primary and key secondary endpoints, %

UPA 45 mg QD at Week 16 (induction)a

(N=125)

UPA 15 mg QD at Week 52 (maintenance)b

(N=34)

UPA 30 mg QD at Week 52 (maintenance)b

(N=39)

Primary endpoint: Clinical remissionc

5.6

26.5

43.6

Clinical responsed

58.4

(N=25)

49.1

(N=32)

78.1

No abdominal pain

40.0

38.2

48.7

No bowel urgency

30.4

32.4

59.0

Endoscopic improvemente

Endoscopic remissionf

14.3

4.9

34.3

12.2

51.3

17.9

Histologic-endoscopic mucosal improvementg

Mucosal healingh

11.0

3.4

21.9

12.0

41.0

12.8

Among patients who achieved clinical remission at the end of induction:

Clinical remissionc

Clinical remissionc and corticosteroid free for ≥90 days immediately prior to Week 52

N/A

(N=3)

(N=4)

100

Among patients who achieved endoscopic improvement at the end of induction:

Endoscopic improvemente

N/A

(N=7)

42.9

(N=9)

66.7

Data are presented for the ITT population comprising patients who achieved a clinical response with 16-week UPA 45 mg QD induction therapy and were re-randomized to receive UPA 15 mg or 30 mg QD maintenance therapy.

aTwo patients were excluded from analysis owing to site non-compliance as prespecified in the statistical analysis plan.

bIncluded patients who had completed, or had the potential to complete, 52 weeks’ maintenance treatment.

cPer Adapted Mayo score ≤2: stool frequency subscore ≤1 and not greater than induction baseline, RBS=0, and ES ≤1.

dInduction therapy (UPA 45 mg QD): Clincal response, defined as a decrease in Adapted Mayo score ≥2 and ≥30% from induction baseline, plus a decrease in RBS ≥1 or an absolute RBS ≤1, at Week 16. Maintenance therapy (UPA 15 mg or 30 mg, QD): Maintenance of clinical response at Week 52 among patients who achieved clinical response at the end of the 16-week induction therapy.

eES ≤1.

fES=0.

gES ≤1 and Geboes score ≤3.1.

hES=0 and Geboes score < 2.

ES, endoscopic subscore; ITT, intent-to-treat; N/A, not applicable; QD, once daily; RBS, rectal bleeding subscore; UPA, upadacitinib.

Disclosures:

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.

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.

Wen Zhou: AbbVie – Employee, Stock Options.

Justin Klaff: AbbVie – Employee, Stock Options.

Dapo Ilo: AbbVie – Employee, Stock Options.

Xuan Yao: AbbVie – Employee, Stock Options.

Gweneth Levy: 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.

Edward Loftus: AbbVie – Consultant, Grant/Research Support. Amgen – Consultant, Grant/Research Support. Arena Pharmaceuticals – Consultant. Boehringer Ingelheim – Consultant. Bristol-Myers Squibb – Consultant, Grant/Research Support. Calibr – Consultant. Celgene – Consultant, Grant/Research Support. Eli Lilly – Consultant. Genentech – Consultant, Grant/Research Support. Gilead – Consultant, Grant/Research Support. Iterative Scopes – Consultant. Janssen – Consultant, Grant/Research Support. Morphic – Consultant. Ono Pharma – Consultant. Pfizer – Consultant, Grant/Research Support. Protagonist – Consultant. Receptos – Grant/Research Support. Robarts Clinical Trials – Grant/Research Support. Scipher Medicine – Consultant. Sun Pharma – Consultant. Surrozen – Consultant. Takeda – Consultant, Grant/Research Support. Theravance – Grant/Research Support. UCB – Consultant, Grant/Research Support.

Séverine Vermeire: AbbVie – Consultant, Grant/Research Support. Arena – Consultant. Celgene – Consultant. Eli Lilly – Consultant. Ferring – Consultant. Galapagos – Consultant. Genentech/Roche – Consultant. Gilead – Consultant. Hospira – Consultant. Janssen – Consultant. Johnson & Johnson – Grant/Research Support. MSD – Consultant. Mundipharma – Consultant. Pfizer – Consultant, Grant/Research Support. Progenity – Consultant. Second Genome – Consultant. Shire – Consultant. Takeda – Consultant, Grant/Research Support.

Remo Panaccione, MD¹, Silvio Danese, MD, PhD², Wen Zhou, MD, PhD³, Justin Klaff, MD⁴, Dapo Ilo, MBBS, MRCS, MSc⁴, Xuan Yao, PhD⁴, Gweneth Levy, MD⁴, Peter D. Higgins, MD, PhD, MSc⁵, Edward V. Loftus, MD, FACG⁶, Séverine Vermeire, MD, PhD⁷, 61, Efficacy and Safety of Upadacitinib in Patients With Moderate to Severe Active Ulcerative Colitis Receiving 16 Weeks Extended Induction Treatment Followed by 52 Weeks Maintenance Treatment in U-ACHIEVE/U-ACCOMPLISH Trials, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.