P4379 - Efficacy and Safety of Upadacitinib After 3 Years of Treatment in Patients With Moderately to Severely Active Ulcerative Colitis: Interim Long-Term Data From the Phase 3 Open-Label Extension Study (U-ACTIVATE)

Tuesday, October 29, 2024

10:30 AM – 4:00 PM ET

Location: Exhibit Hall E

Has Audio

Presenting Author(s)

Remo Panaccione, MD

University of Calgary
Calgary, AB, Canada

Remo Panaccione, MD¹, Peter Higgins, MD², Hiroshi Nakase, MD³, Sarah C. Glover, DO⁴, Silvio Danese, MD, PhD⁵, Jean-Frédéric Colombel, MD⁶, Jason Eccleston, MD⁷, Michelle Kujawski, PhD⁷, Valencia Remple, PhD⁷, Xuan Yao, PhD⁷, Smitha Suravaram, MD⁷, Stefan Schreiber, MD⁸
¹University of Calgary, Calgary, AB, Canada; ²University of Michigan, Ann Arbor, MI; ³Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan; ⁴Tulane University School of Medicine, New Orleans, LA; ⁵Humanitas Clinical and Research Center - IRCCS, Rozzano and Humanitas University, Pieve Emanuele, Milan, Lombardia, Italy; ⁶Icahn School of Medicine at Mount Sinai, New York, NY; ⁷AbbVie Inc., North Chicago, IL; ⁸University Hospital, Kiel, Schleswig-Holstein, Germany

Introduction: Long-term efficacy and safety has been established for upadacitinib (UPA), an oral, reversible JAK inhibitor, through studies of multiple autoimmune conditions.

Methods: Efficacy and safety of UPA are reported after almost 3 years (yrs) of therapy in patients (pts) with moderately to severely active ulcerative colitis (UC) from the U-ACTIVATE study, including 1 yr maintenance and 96 weeks (wks) of long-term extension (LTE). Pts aged 16–75 yrs with UC for ≥90 days prior to study entry, Adapted Mayo score (AMS) of 5–9, and endoscopic subscore of 2 or 3 were eligible for induction studies (U-ACCOMPLISH; U-ACHIEVE) and randomized to placebo (PBO) or UPA 45 mg once daily (QD) for 8 wks. Clinical responders were re-randomized to PBO, UPA 15 mg QD (UPA15) or UPA 30 mg QD (UPA30) for 52 wks maintenance (U-ACHIEVE). Pts completing maintenance were eligible to enter LTE on their maintenance dose. Efficacy was evaluated by clinical remission (per AMS and Partial Mayo score), maintenance of clinical remission per AMS, clinical response, endoscopic remission, endoscopic improvement and maintenance of endoscopic remission at LTE Wk96 (Table). Safety was assessed by treatment-emergent adverse events (TEAEs) and exposure-adjusted event rates (EAERs). Data (cutoff: June 30, 2023) were analyzed as observed without imputation for missing values.

Results: At LTE Wk96, about 75% of UPA-treated pts achieved clinical remission (Table). Of pts in clinical remission at LTE Wk0, a similar proportion maintained response with UPA15 and slightly higher response rate was observed with UPA30 at LTE Wk96. Clinical outcomes and endoscopic improvement were observed in the majority of pts in both UPA groups. Endoscopic remission was achieved by almost half of pts treated with UPA. Of endoscopic remitters at LTE Wk0, more than half maintained remission status at LTE Wk96, with slightly higher response rate observed with UPA30. For safety, 369 pts with 789.4 patient-years (PY) of exposure were analyzed (Table). Rates of serious TEAEs and TEAEs leading to treatment discontinuation were similar across treatment groups. No deaths were reported with UPA15; 1 TEAE leading to death with UPA30 (EAER: 0.2 E/100 PY) occurred in a pt requiring prolonged hospitalization for worsening COVID-19 infection.

Discussion: Continued benefit of UPA therapy after almost 3 years in pts with UC was observed by achievement of clinical and endoscopic endpoints at LTE Wk96. The long-term safety profile for UPA was consistent with previous findings.

Note: The table for this abstract can be viewed in the ePoster Gallery section of the ACG 2024 ePoster Site or in The American Journal of Gastroenterology's abstract supplement issue, both of which will be available starting October 27, 2024.

Disclosures:

Remo Panaccione: Élan – Consultant. Abbivax – Consultant. Abbott – Consultant. AbbVie – Advisory Committee/Board Member, Consultant, Speaking Fees. Alimentiv – Advisory Committee/Board Member, Consultant. Amgen – Advisory Committee/Board Member, Consultant, Speaker Fees. Arena Pharmaceuticals – Advisory Committee/Board Member, Consultant, Speaker Fees. AstraZeneca – Advisory Committee/Board Member, Consultant. Biogen – Advisory Committee/Board Member, Consultant. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant, Speaker Fees. Celgene – Advisory Committee/Board Member, Consultant, Speaker Fees. Celltrion – Consultant. Cosmos Pharmaceuticals – Consultant. Eisai – Consultant. Ferring – Advisory Committee/Board Member, Consultant, Speaker Fees. Fresenius Kabi – Advisory Committee/Board Member, Consultant, Speaker Fees. Galapagos – Consultant. Genentech – Advisory Committee/Board Member, Consultant. Gilead – Advisory Committee/Board Member, Consultant, Speaker Fees. GlaxoSmithKline – Advisory Committee/Board Member, Consultant. JAMP Bio – Advisory Committee/Board Member, Consultant. Janssen – Advisory Committee/Board Member, Consultant, Speaker Fees. Lilly – Advisory Committee/Board Member, Consultant, Speaker Fees. Merck – Advisory Committee/Board Member, Consultant, Speaker Fees. Mylan – Advisory Committee/Board Member, Consultant. Novartis – Advisory Committee/Board Member, Consultant. Oppilan Pharma – Advisory Committee/Board Member, Consultant. Organon – Advisory Committee/Board Member, Consultant, Speaker Fees. Pandion Pharma – Advisory Committee/Board Member, Consultant. Pendopharm – Consultant. Pfizer Inc – Advisory Committee/Board Member, Consultant, Speaker Fees. Progenity – Advisory Committee/Board Member, Consultant. Prometheus Biosciences – Consultant. Protagonist Therapeutics – Advisory Committee/Board Member, Consultant. Roche – Advisory Committee/Board Member, Consultant, Speaker Fees. Sandoz – Advisory Committee/Board Member, Consultant, Speaker Fees. Satisfai Health – Consultant. Shire – Advisory Committee/Board Member, Consultant, Speaker Fees. Sublimity Therapeutics – Advisory Committee/Board Member, Consultant. Takeda – Advisory Committee/Board Member, Consultant, Speaker Fees. Theravance – Consultant. Trellus – Consultant. UCB – Consultant. Ventyx – Advisory Committee/Board Member, Consultant. Viatris – Consultant.

Peter Higgins: AbbVie – Grant/Research Support. Connectome Coordination Facility – Grant/Research Support. GI Health Foundation – Consultant. Imedex – Consultant. Lilly – Consultant. National Institute of Health and Takeda – Grant/Research Support. Pfizer – Consultant. Takeda – Consultant. Vindico Medical Education – Consultant.

Hiroshi Nakase: AbbVie – Grant/Research Support. Boehringer Ingelheim – Grant/Research Support. Bristol Myers Squibb – Grant/Research Support. Celgene – Grant/Research Support. Daiichi Sankyo Company – Grant/Research Support. EA Pharma – Grant/Research Support. Hoya Group Pentax Medical – Grant/Research Support. Janssen – Grant/Research Support. JIMRO – Grant/Research Support. Kissei Pharmaceutical – Grant/Research Support. Kyorin Pharmaceutical – Grant/Research Support. Mitsubishi Tanabe Pharma Corporation – Grant/Research Support. Mochida Pharmaceutical – Grant/Research Support. Nippon Kayaku – Grant/Research Support. Pfizer – Grant/Research Support. Takeda – Grant/Research Support. Zeria – Grant/Research Support.

Sarah C. Glover indicated no relevant financial relationships.

Silvio Danese: AbbVie – Consultant, Speakers Bureau. Alimentiv – Consultant. Allergan – Consultant. Amgen – Consultant, Speakers Bureau. Applied Molecular Transport – Consultant. AstraZeneca – Consultant. Athos Therapeutics – Consultant. Biogen – Consultant. Boehringer Ingelheim – Consultant. Bristol Myers Squibb – Consultant. Celgene – Consultant. Celltrion Healthcare – Consultant. Dr Falk Pharma – Consultant. Eli Lilly and Company – Consultant. Enthera – Consultant. Ferring – Consultant, Speakers Bureau. Gilead – Consultant, Speakers Bureau. Hospira – Consultant. Inotrem – Consultant. Janssen – Consultant, Speakers Bureau. Johnson & Johnson – Consultant. Morphic – Consultant. MSD – Consultant. Mundipharma – Consultant. Mylan – Consultant, Speakers Bureau. Pfizer Inc – Consultant, Speakers Bureau. Roche – Consultant. Sandoz – Consultant. Sublimity Therapeutics – Consultant. Takeda – Consultant, Speakers Bureau. Teladoc Health – Consultant. TiGenix – Consultant. UCB Inc. – Consultant. Vial – Consultant. Vifor – Consultant.

Jean-Frédéric Colombel: AbbVie – Consultant, Grant/Research Support. Allergan – Consultant. Amgen – Consultant. AnaptysBio – Consultant. Arena Pharmaceuticals – Consultant. Boehringer Ingelheim – Consultant. Bristol Myers Squib – Consultant, Grant/Research Support. Celgene – Consultant. Celltrion – Consultant. Eli Lilly – Consultant. Enterome – Consultant. Ferring – Consultant. Galmed Research – Consultant. Genentech – Consultant. Genfit – Stock-publicly held company(excluding mutual/index funds). Glaxo Smith Kline – Consultant. Immunic – Consultant. Intestinal Biotech Development – Stock-publicly held company(excluding mutual/index funds). Iterative Scopes – Consultant. Janssen – Consultant, Grant/Research Support. Johnson & Johnson – Consultant, Grant/Research Support. Kaleido Biosciences – Consultant. Landos – Consultant. MedImmune – Consultant. Merck – Consultant. Microba Life Science – Consultant. Novartis – Consultant. Otsuka Pharmaceutical – Consultant. Pfizer – Consultant. PPM Services – Consultant. Protagonist – Consultant. Sanofi – Consultant. Second Genome – Consultant. Seres – Consultant. Shire – Consultant. Takeda – Consultant, Grant/Research Support. Theradiag – Consultant. TiGenix – Consultant. Vifor – Consultant.

Jason Eccleston: AbbVie – Employee.

Michelle Kujawski: AbbVie – Employee, Stock Options.

Valencia Remple: AbbVie – Employee, Stock-publicly held company(excluding mutual/index funds).

Xuan Yao: AbbVie – Employee.

Smitha Suravaram: AbbVie – Employee, Stock Options.

Stefan Schreiber: AbbVie – Consultant, Personal fees, Speakers Bureau. Amgen – Personal fees. Arena Pharmaceuticals – Consultant, Personal fees, Speakers Bureau. Biogen – Consultant, Personal fees, Speakers Bureau. Bristol Myers Squibb – Consultant, Personal fees, Speakers Bureau. Celgene – Consultant, Personal fees, Speakers Bureau. Celltrion – Consultant, Personal fees, Speakers Bureau. Eli Lilly and Company – Personal fees. Falk – Consultant, Personal fees, Speakers Bureau. Ferring Pharmaceuticals – Personal fees. Fresenius – Consultant, Personal fees, Speakers Bureau. Galapagos – Personal fees. Gilead – Consultant, Personal fees. Hikma Pharmaceuticals – Advisory Committee/Board Member, Consultant. I-MAB – Consultant, Personal fees. Janssen – Consultant, Personal fees, Speakers Bureau. Morphic – Personal fees. MSD – Consultant, Personal fees, Speakers Bureau. Mylan – Consultant, Personal fees. Novartis – Personal fees. Pfizer Inc – Consultant, Personal fees, Speakers Bureau. Protagonist – Consultant, Personal fees. Provention Bio – Consultant, Personal fees. Roche – Personal fees. Sandoz/Hexal – Personal fees. Shire – Personal fees. Takeda – Consultant, Personal fees, Speakers Bureau. Theravance Biopharma – Consultant, Personal fees. Ventyx – Consultant, Personal fees.