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Poster Session A - Sunday Afternoon

Category: IBD

A0329 - Benefit–Risk Assessment of Upadacitinib Treatment in Patients With Moderately to Severely Active Ulcerative Colitis

Sunday, October 23, 2022

5:00 PM – 7:00 PM ET

Location: Crown Ballroom

Has Audio

Presenting Author(s)

RV

Ramona Vladea, PhD

AbbVie, Inc.
North Chicago, Illinois

Remo Panaccione, MD¹, Irina Blumenstein, MD², Peter Irving, MD, MA³, Ramona Vladea, PhD⁴, Dapo Ilo, MBBS, MRCS, MSc⁴, Wen Zhou, MD, PhD⁵, Gweneth Levy, MD⁴, Xuan Yao, PhD⁴, Iris Dotan, MD⁶
¹University of Calgary, Calgary, AB, Canada; ²Goethe University Hospital, Frankfurt, Hessen, Germany; ³Guy’s and St. Thomas’ NHS Foundation Trust, London, England, United Kingdom; ⁴AbbVie, Inc., North Chicago, IL; ⁵AbbVie Inc., North Chicago, IL; ⁶Rabin Medical Center, Petah Tikva, Israel and Tel Aviv University, Ramat Aviv, Tel Aviv, Israel

Introduction: Efficacy and safety of upadacitinib(UPA) as induction and maintenance therapy in patients with moderate to severe active ulcerative colitis have been demonstrated in a Phase 3 clinical trial program.^1–3

Methods: Patients with clinical response(per Adapted Mayo score) after 8 weeks (wks) of UPA 45mg once daily(QD) induction treatment in U-ACHIEVE Induction(NCT02819635) or U-ACCOMPLISH(NCT03653026) were re-randomized to U‑ACHIEVE Maintenance(NTC02819635) receiving UPA 15mg QD, UPA 30mg QD, or placebo(PBO) maintenance therapy. We present 52wk efficacy and safety benefit–risk assessment of UPA 15mg and UPA 30mg vs PBO. For efficacy outcomes, point estimates and 95% confidence intervals(CI) of PBO-adjusted treatment effect were calculated. For risk analysis, exposure-adjusted event rates(events per 100 patient-years [E/100 PY]) of selected adverse events of special interest were evaluated.

Results: Overall, 681 patients were analyzed for efficacy(UPA 15mg, 225; UPA 30mg, 233; PBO, 223). For primary endpoint of clinical remission at wk 52, point estimates of PBO-adjusted treatment effect were 30.1%(95% CI: 22.7, 37.4) with UPA 15mg and 42.9%(35.4, 50.4) with UPA 30mg(p< 0.001 for both; Table). Significant differences were observed across secondary endpoints for UPA doses vs PBO(all p< 0.001; Table). Rates of serious infections were 5.9 E/100 PY with PBO vs 5.0 and 3.2 for UPA 15mg and UPA 30mg, respectively. No events of herpes zoster were reported with PBO, while rates with UPA 15mg and UPA 30mg were 6.0 and 7.3 E/100 PY, respectively. Rates of malignancy excluding non-melanoma skin cancer were 0.7 E/100 PY with PBO vs 0.5 and 0.9 with UPA 15mg and UPA 30mg, respectively; rates of non-melanoma skin cancer were 1.4 E/100 PY with UPA 30mg, with no cases reported with UPA 15mg or PBO. Adjudicated venous thromboembolic events were low in UPA groups and no cases were reported with PBO; adjudicated major adverse cardiovascular events were low with PBO and UPA 30mg, and none with UPA 15mg(Table).

Discussion: Response rates were significantly greater with UPA 15mg and UPA 30mg versus PBO across endpoints assessed. UPA doses were well tolerated. Rates of herpes zoster and creatine phosphokinase elevation, known safety signals of JAK inhibitors,⁴ were dose-dependent. The data suggest that UPA 15mg and UPA 30mg QD have a favorable benefit–risk profile after 52wks maintenance therapy. The safety of UPA continues to be monitored in long-term extension study.

Primary and key secondary endpoints at Week 52

UPA 15 mg QD – PBO
response rate difference,
% (95% CI)^a

UPA 30 mg QD – PBO
response rate difference,
% (95% CI)^a

Clinical remission^b

Endoscopic improvement^c

Maintenance of clinical remission^d

Corticosteroid-free clinical remission^e

Maintenance of endoscopic improvement^f

Endoscopic remission^g

Histologic-endoscopic mucosal improvement^h

Mucosal healingⁱ

30.1 (22.7, 37.4)***

34.4 (26.7, 42.1)***

34.9 (21.2, 48.5)***

33.7 (20.0, 47.3)***

42.2 (30.4, 53.9)***

18.6 (12.2, 25.0)***

28.5 (21.1, 35.9)***

13.5 (7.8, 19.3)***

42.9 (35.4, 50.4)***

49.0 (41.4, 56.7)***

46.9 (34.0, 59.8)***

45.5 (32.6, 58.5)***

51.5 (40.9, 62.1)***

21.9 (15.4, 28.5)***

43.8 (36.1, 51.5)***

17.2 (11.2, 23.3)***

Selected adverse events of special interest^j

PBO,
E (E/100 PY)
(N=245)

UPA 15 mg QD,
E (E/100 PY)

(N=250)

UPA 30 mg QD,
E (E/100 PY)

(N=251)

Serious infection

Herpes zoster

CPK elevation

Malignancy (excluding NMSC)

NMSC

Adjudicated MACE

Adjudicated VTE

8 (5.9)

5 (3.7)

1 (0.7)

10 (5.0)

12 (6.0)

16 (8.0)

1 (0.5)

2 (1.0)

7 (3.2)

16 (7.3)

22 (10.1)

2 (0.9)

3 (1.4)

1 (0.5)

2 (0.9)

***p< 0.001.
^aThe efficacy analysis was based on the ITT population. Results are based on non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19. The point estimate and 95% CI for treatment difference are based on Cochran–Mantel–Haenszel tests adjusted for strata (corticosteroid use at Week 0 [yes or no], clinical remission status at Week 0 [yes or no], biologic-IR status at baseline [biologic-IR or non-biologic-IR]).
^bStool frequency subscore ≤1 and not greater than baseline (of induction), RBS=0, and ES ≤1.
^cES ≤1.
^dAmong patients with clinical remission at the end of the induction therapy.
^eClinical remission at Week 52 and corticosteroid free for ≥90 days prior to Week 52 among patients with clinical remission at the end of the induction therapy.
^fEndoscopic improvement at Week 52 among patients with endoscopic improvement at the end of the induction therapy.

^gES=0.

^hES ≤1 and Geboes score ≤3.1.

ⁱES=0 and Geboes score < 2.

^jThe safety analysis included all patients who received ≥1 dose of study therapy (ITT population plus patients who received up to 44 weeks’ maintenance therapy under earlier versions of protocol amendments).

CI, confidence interval; CPK, creatine phosphokinase; E, event; ES, endoscopic subscore; IR, inadequate responder; ITT, intention-to-treat; MACE, major adverse cardiovascular event; NMSC, non-melanoma skin cancer; QD, once daily; PBO, placebo; PY, patient-years; RBS, rectal bleeding subscore; UPA, upadacitinib; VTE, venous thromboembolic event.

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.

Irina Blumenstein: AbbVie – Consultant, Speakers Bureau. Amgen – Consultant, Speakers Bureau. Arena – Consultant, Speakers Bureau. Biogen – Consultant, Speakers Bureau. Bristol Myers Squibb – Consultant, Speakers Bureau. Celgene – Speakers Bureau. Celltrion – Consultant, Speakers Bureau. Ferring – Consultant, Speakers Bureau. Galapagos – Consultant, Speakers Bureau. Janssen – Consultant, Speakers Bureau. Mylan – Speakers Bureau. Pfizer – Consultant, Speakers Bureau. Shire – Consultant, Speakers Bureau. Takeda – Consultant, Speakers Bureau.

Peter Irving: AbbVie – Advisory Committee/Board Member, Speakers Bureau. Arena – Advisory Committee/Board Member. Boehringer Ingelheim – Advisory Committee/Board Member. Bristol Myers Squibb – Advisory Committee/Board Member. Celgene – Advisory Committee/Board Member, Speakers Bureau. Celltrion – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. Dr Falk Pharma – Speakers Bureau. Eli Lilly – Advisory Committee/Board Member. Ferring – Speakers Bureau. Galapagos – Speakers Bureau. Genentech – Advisory Committee/Board Member. Gilead – Advisory Committee/Board Member, Speakers Bureau. Hospira – Advisory Committee/Board Member. Janssen – Advisory Committee/Board Member, Speakers Bureau. MSD – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. Pfizer – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. Pharmacosmos – Advisory Committee/Board Member. Prometheus Biosciences – Advisory Committee/Board Member. Roche – Advisory Committee/Board Member. Samsung Bioepis – Advisory Committee/Board Member. Sandoz – Advisory Committee/Board Member, Speakers Bureau. Sapphire Medical – Speakers Bureau. Shire – Speakers Bureau. Takeda – Advisory Committee/Board Member, Grant/Research Support. Tillotts – Speakers Bureau. Topivert – Advisory Committee/Board Member. VH2 – Advisory Committee/Board Member. Vifor – Advisory Committee/Board Member. Warner Chilcott – Advisory Committee/Board Member, Speakers Bureau.

Ramona Vladea: AbbVie – Employee, Stock Options.

Dapo Ilo: AbbVie – Employee, Stock Options.

Wen Zhou: AbbVie – Employee, Stock Options.

Gweneth Levy: AbbVie – Employee, Stock Options.

Xuan Yao: AbbVie – Employee, Stock Options.

Iris Dotan: Abbott – Consultant, Grant/Research Support, Honorarium. Abbvie – Consultant, Grant/Research Support, Honorarium. Altman – Consultant, Grant/Research Support, Honorarium. Arena – Consultant, Grant/Research Support, Honorarium. Athos – Consultant, Grant/Research Support, Honorarium. Cambridge Healthcare – Consultant, Grant/Research Support, Honorarium. Celgene/BMS – Consultant, Grant/Research Support, Honorarium. Celltrion – Consultant, Grant/Research Support, Honorarium. Falk Pharma – Consultant, Grant/Research Support, Honorarium. Ferring – Consultant, Grant/Research Support, Honorarium. Food Industries Organisation – Consultant, Grant/Research Support, Honorarium. Galapagos – Consultant, Grant/Research Support, Honorarium. Genentech/Roche – Consultant, Grant/Research Support, Honorarium. Gilead – Consultant, Grant/Research Support, Honorarium. GSK – Consultant, Grant/Research Support, Honorarium. Hospital for Sick Children – Consultant, Grant/Research Support, Honorarium. Integra Holdings – Consultant, Grant/Research Support, Honorarium. Iterative Scopes – Consultant, Grant/Research Support, Honorarium. Janssen – Consultant, Grant/Research Support, Honorarium. Mediahuset – Consultant, Grant/Research Support, Honorarium. Medscape – Consultant, Grant/Research Support, Honorarium. Neopharm – Consultant, Grant/Research Support, Honorarium. Peer voice – Consultant, Grant/Research Support, Honorarium. Pfizer Inc – Consultant, Grant/Research Support, Honorarium. Sangamo – Consultant, Grant/Research Support, Honorarium. Sublimity – Consultant, Grant/Research Support, Honorarium. Takeda – Consultant, Grant/Research Support, Honorarium. Wilbio – Consultant, Grant/Research Support, Honorarium.

Remo Panaccione, MD¹, Irina Blumenstein, MD², Peter Irving, MD, MA³, Ramona Vladea, PhD⁴, Dapo Ilo, MBBS, MRCS, MSc⁴, Wen Zhou, MD, PhD⁵, Gweneth Levy, MD⁴, Xuan Yao, PhD⁴, Iris Dotan, MD⁶. A0329 - Benefit–Risk Assessment of Upadacitinib Treatment in Patients With Moderately to Severely Active Ulcerative Colitis, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.