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Poster Session B - Monday Morning

B0364 - Matching-Adjusted Indirect Comparison of Upadacitinib versus Vedolizumab as Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis

Monday, October 24, 2022

10:00 AM – 12:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

David T. Rubin, MD, FACG

University of Chicago Medicine Inflammatory Bowel Disease Center
Chicago, IL

Walter Reinisch, MD, PhD¹, Séverine Vermeire, MD, PhD², Charlotte Hedin, PhD³, David T. Rubin, MD, FACG⁴, Julian Panés, MD, PhD⁵, Huiwen Deng, PharmD⁶, Si Xuan, PhD⁷, Lani Wegrzyn, ScD⁷, John Liu, MD, MS⁷, Dapo Ilo, MBBS, MRCS, MSc⁷, Wen Zhou, MD, PhD⁸, Yuri Sanchez-Gonzalez, PhD⁷, Remo Panaccione, MD⁹
¹Medical University of Vienna, Vienna, Wien, Austria; ²University Hospitals Leuven, Leuven, Brussels Hoofdstedelijk Gewest, Belgium; ³Karolinska Institutet and Karolinska University Hospital, Stockholm, Stockholms Lan, Sweden; ⁴University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL; ⁵Formerly, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Catalonia, Spain; ⁶AbbVie, Inc. and University of Illinois at Chicago, Chicago, IL; ⁷AbbVie, Inc., North Chicago, IL; ⁸AbbVie Inc., North Chicago, IL; ⁹University of Calgary, Calgary, AB, Canada

Introduction: Aim is to conduct placebo(PBO)-anchored matching-adjusted indirect comparison (MAIC) of efficacy and safety outcomes between upadacitinib(UPA) and vedolizumab(VEDO) in patients(pts) with moderate to severe active UC.

Methods: Data from phase 3 induction studies U-ACHIEVE Induction, U‑ACCOMPLISH, and GEMINI 1 were used. Pts received UPA 45mg oral, once daily for 8 weeks; VEDO 300mg intravenous, at weeks 0 and 2; or corresponding PBO. Baseline characteristics for age, gender, duration of disease, total Mayo score, corticosteroid use, and fecal calprotectin levels from UPA trials were weighted to match that reported for pts in GEMINI for efficacy and previous anti-tumor necrosis factor/biologic therapy use/failure, Inflammatory Bowel Disease Questionnaire score, hemoglobin concentration, and white-cell count for safety. MAIC was done for bio-naïve(no exposure to any biologic at baseline) and bio-failure(inadequate response, loss of response, or intolerance to biologic treatment at baseline) pts for efficacy outcomes and all pts for safety outcomes. Efficacy outcomes evaluated at Week 6(VEDO)/Week 8(UPA) were clinical remission per full Mayo score(FMS; FMS≤2 with no subscore >1), clinical response per FMS(decrease from baseline in FMS≥3 points and ≥30%, accompanied by decrease in rectal bleeding score [RBS] of ≥1 or absolute RBS of 0 or 1), and endoscopic improvement(endoscopic subscore 0 or 1). Safety outcomes were all adverse events(AEs), serious AEs(SAEs), and serious infections.

Results: MAIC used data from 833 UPA pts and 351 VEDO pts for efficacy; 848 and 374 pts for safety. A significantly greater proportion of pts receiving UPA vs VEDO in bio-naïve and bio-failure groups achieved clinical remission, clinical response, and endoscopic improvement after weighting(P < 0.05, Table). Rate differences between UPA and VEDO cohorts for clinical remission, clinical response, and endoscopic improvement were 0.160, 0.173, and 0.270, respectively, for bio-naïve group and 0.141, 0.374, and 0.191 for bio-failed cohort. Safety outcomes, including rates of AEs, SAEs, and serious infections, were not significantly different between UPA and VEDO.

Discussion: Greater clinical efficacy with comparable safety was achieved during induction treatment with UPA vs VEDO for pts with moderate to severe active UC based on MAIC, given caveat of differences in onset of action rates and assessment times of the drugs. Additional MAIC to assess longer-term outcomes are warranted.

Efficacy/ safety outcome

Treatment

Rate^a,b,c

(Bio-naïve^d)

Rate difference

(95% CI)

UPA or VEDO vs PBO

(Bio-naïve^d)

Rate difference

(95% CI)

UPA vs VEDO

(Bio-naïve^d)

Rate^{a, b,c}

(Bio-failed)

Rate difference (95% CI)

UPA or VEDO vs PBO

(Bio-failed)

Rate difference

(95% CI)

UPA vs VEDO

(Bio-failed)

Clinical remission

UPA 45 mg /PBO

37.9%/5.4%

0.325

(0.245, 0.405)

0.160**

(0.038, 0.282)

20.7%/0.0%

0.207

(0.156, 0.257)

0.141**

(0.048, 0.233)

VEDO 300 mg /PBO

23.1%/6.6%

0.165

(0.074, 0.256)

9.8%/3.2%

0.066

(−0.012, 0.143)

Clinical response

UPA 45 mg /PBO

81.4%/37.3%

0.441

(0.332, 0.549)

0.173*

(0.003, 0.343)

65.4%/9.6%

0.558

(0.479, 0.637)

0.374***

(0.208, 0.540)

VEDO 300 mg /PBO

53.1%/26.3%

0.268

(0.137, 0.399)

39.0%/20.6%

0.184

(0.038, 0.329)

Endoscopic improve-ment

UPA 45 mg /PBO

61.5%/10.3%

0.512

(0.422, 0.601)

0.270***

(0.112, 0.427)

33.0%/4.0%

0.290

(0.221, 0.358)

0.191*

(0.034, 0.348)

VEDO 300 mg /PBO

49.2%/25.0%

0.242

(0.112, 0.372)

30.5%/20.6%

0.099

(−0.043, 0.240)

AE/SAE/

Serious infections

(overall population)

UPA 45 mg /PBO

AE: 55.0%/50.2%

SAE: 2.9%/3.8%

Serious infections:

0.6%/0.4%

AE:

0.048

(−0.040, 0.136)

SAE:

−0.009

(−0.042, 0.023)

Serious infections:

0.001

(−0.011, 0.014)

AE:

0.111

(−0.024, 0.246)

SAE:

0.036

(−0.019, 0.091)

Serious infections:

0.017

(−0.010, 0.044)

VEDO 300 mg /PBO

AE:

40.0%/46.3%

SAE:

2.2%/6.7%

Serious infections:

0.4%/2.0%

AE:

−0.063

(−0.166, 0.039)

SAE:

−0.045

(−0.089, 0.000)

Serious infections:

−0.016

(−0.040, 0.008)

^aAfter weighting. ^bAggregated numbers from both induction studies. ^cUPA data are individual level results while VEDO data are aggregated. ^dEfficacy outcomes are based on bio-naïve pts and safety outcomes are based on the overall population. P‑value equals *< 0.05, **≤0.01, ***< 0.001. Patient number (bio-naïve/bio-failed/all pts-safety):

UPA 45 mg (262/292/562), placebo-UPA (132/147/286), VEDO (130/82/225), placebo-VEDO (76/63/149). AE, all adverse events; PBO, placebo; pts, patients; SAE, serious adverse events; UPA, upadacitinib; VEDO, vedolizumab

Disclosures:

Walter Reinisch: 4SC – Advisory Committee/Board Member, Consultant. Abbott Laboratories – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. AbbVie – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Aesca – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Algernon – Consultant. AM Pharma – Advisory Committee/Board Member, Consultant. Amgen – Advisory Committee/Board Member, Consultant. AMT – Consultant. AOP Orphan – Consultant. Aptalis – Speakers Bureau. Arena Pharmaceuticals – Consultant. Astellas – Advisory Committee/Board Member, Consultant, Speakers Bureau. AstraZeneca – Advisory Committee/Board Member, Consultant. Avaxia – Advisory Committee/Board Member, Consultant. Bioclinica – Consultant. Biogen IDEC – Advisory Committee/Board Member, Consultant. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant. Celgene – Advisory Committee/Board Member, Consultant. Cellerix – Advisory Committee/Board Member, Consultant. Celltrion – Advisory Committee/Board Member, Consultant, Speakers Bureau. Centocor – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. ChemoCentryx – Advisory Committee/Board Member, Consultant. Covance – Consultant. Danone Austria – Advisory Committee/Board Member, Consultant, Speakers Bureau. DSM – Advisory Committee/Board Member, Consultant. Elan – Advisory Committee/Board Member, Consultant, Speakers Bureau. Eli Lilly – Consultant. Ernest & Young – Consultant. Falk Pharma GmbH – Consultant, Grant/Research Support, Speakers Bureau. Ferring – Advisory Committee/Board Member, Consultant, Speakers Bureau. Galapagos – Advisory Committee/Board Member, Consultant. Gatehouse Bio – Consultant. Genentech – Advisory Committee/Board Member, Consultant. Gilead – Consultant. Grünenthal – Advisory Committee/Board Member, Consultant. ICON – Consultant. Immundiagnostik – Grant/Research Support, Speaker. Index Pharma – Consultant. Inova – Advisory Committee/Board Member, Consultant. Intrinsic Imaging – Consultant. Janssen – Advisory Committee/Board Member, Consultant, Grant/Research Support. Johnson & Johnson – Advisory Committee/Board Member, Consultant. Kyowa Hakko Kirin Pharma – Advisory Committee/Board Member, Consultant. Lipid Therapeutics – Advisory Committee/Board Member, Consultant. LivaNova – Consultant. Mallinckrodt – Consultant. Medahead – Consultant. MedImmune – Advisory Committee/Board Member, Consultant. Millenium – Advisory Committee/Board Member, Consultant. Mitsubishi Tanabe Pharma Corporation – Advisory Committee/Board Member, Consultant, Speakers Bureau. MSD – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Nash Pharmaceuticals – Consultant. Nestle – Advisory Committee/Board Member, Consultant. Nippon Kayaku – Consultant. Novartis – Advisory Committee/Board Member, Consultant. Ocera – Advisory Committee/Board Member, Consultant. OMass – Consultant. Otsuka – Advisory Committee/Board Member, Consultant, Speakers Bureau. Parexel – Consultant. PDL – Advisory Committee/Board Member, Consultant, Speakers Bureau. Periconsulting – Consultant. Pfizer – Advisory Committee/Board Member, Consultant. Pharmacosmos – Advisory Committee/Board Member, Consultant, Speakers Bureau. Philip Morris Institute – Consultant. PLS Education – Speakers Bureau. Procter & Gamble – Advisory Committee/Board Member, Consultant. Prometheus – Advisory Committee/Board Member, Consultant. Protagonist – Consultant. Provention – Consultant. Quell Therapeutics – Consultant. Robarts Clinical Trial – Consultant. Roland Berger GmbH – Consultant. Sandoz – Advisory Committee/Board Member, Consultant, Grant/Research Support. Schering-Plough – Advisory Committee/Board Member, Consultant, Speakers Bureau. Second Genome – Advisory Committee/Board Member, Consultant. Seres Therapeutics – Consultant. Setpoint Medical – Advisory Committee/Board Member, Consultant. Shire – Speakers Bureau. Sigmoid – Consultant. Sublimity – Consultant. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Therakos – Advisory Committee/Board Member, Consultant, Speakers Bureau. Theravance – Consultant. TiGenix – Advisory Committee/Board Member, Consultant. UCB – Advisory Committee/Board Member, Consultant. Vifor – Consultant, Speakers Bureau. Yakult – Speakers Bureau. Zealand – Advisory Committee/Board Member, Consultant. Zyngenia – Advisory Committee/Board Member, Consultant.

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.

Charlotte Hedin: AbbVie – Speakers Bureau. Ferring – Speakers Bureau. GlaxoSmithKlein(GSK) – Local principal investigator for clinical trials. Janssen – Local principal investigator for clinical trials, Speakers Bureau. Pfizer – Consultant. Takeda – Speakers Bureau.

David Rubin: AbbVie – Consultant. Alimentiv Inc. – Consultant. AltruBio – Consultant. Arena Pharmaceuticals – Consultant. Aslan Pharmaceuticals – Consultant. Athos Therapeutics – Consultant. Bellatrix Pharmaceuticals – Consultant. Boehringer Ingelheim, Ltd. – Consultant. Bristol Myers Squibb – Consultant. Celgene Corp/Syneos – Consultant. ClostraBio – Consultant. Connect BioPharma – Consultant. EcoR1 – Consultant. Genentech/Roche – Consultant. Gilead Sciences – Consultant. Ironwood Pharmaceuticals – Consultant. Iterative Scopes – Consultant. Janssen – Consultant. Kaleido Biosciences – Consultant. Lilly, Eli & Co – Consultant. Materia Prima – Consultant. Pfizer – Consultant. Prometheus Biosciences – Consultant. Reistone Biopharma – Consultant. Seres Therapeutics, Inc – Consultant. Takeda – Consultant, Grant/Research Support. Target RWE – Consultant. Techlab – Consultant. Trellus Health – Consultant.

Julian Panés: AbbVie – Grant/Research Support, Personal fees. Arena – Personal fees. Athos – Personal fees. Boehringer Ingelheim – Personal fees. Celgene – Personal fees. Celltrion – Personal fees. Ferring Pharmaceuticals – Personal fees. Galapagos – Personal fees. Genentech/Roche – Personal fees. GSK – Personal fees. Immunic – Personal fees. Janssen Pharmaceuticals – Personal fees. Mirum – Personal fees. Morphic – Personal fees. Nestlé – Personal fees. Origo – Personal fees. Pandion – Personal fees. Pfizer Inc – Grant/Research Support, Personal fees. Progenity – Personal fees. Takeda – Personal fees. Theravance Biopharma – Personal fees. Wassermann – Personal fees.

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

Si Xuan: AbbVie – Employee, Stock Options.

Lani Wegrzyn: AbbVie – Employee, Stock Options.

John Liu: AbbVie – Employee, Stock Options.

Dapo Ilo: AbbVie – Employee, Stock Options.

Wen Zhou: AbbVie – Employee, Stock Options.

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

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.