54A - Safety and Efficacy of Ustekinumab Induction Therapy in Patients With Moderate to Severe Ulcerative Colitis: Results From the Phase 3 UNIFI Study (late-breaking abstract)
Tuesday, October 9
3:45 PM - 3:55 PM
Location: Terrace Ballroom 2-3 (level 400)
Bruce E. Sands, MD1, William J. Sandborn, MD2, Remo Panaccione, MD3, Christopher D. O’Brien, MD, PhD4, Hongyan Zhang, PhD4, Jewel Johanns, PhD4, Laurent Peyrin-Biroulet, MD, PhD5, Gert van Assche, MD, PhD6, Silvio Danese, MD, PhD7, Stephan Targan, MD8, Maria T Abreu, MD9, Tadakazu Hisamatsu, MD, PhD10, Philippe Szapary, MD4, Colleen Marano, PhD4
1Icahn School of Medicine at Mount Sinai, New York, NY; 2University of California San Diego, La Jolla, CA; 3University of Calgary, Calgary, AB, Canada; 4Janssen Research & Development, LLC, Spring House, PA; 5Nancy University Hospital, Université de Lorraine, Nancy, France; 6University of Leuven, Louvain, Belgium; 7Humanitas Research Hospital, Milano, Italy; 8Cedars Sinai Medical Center, Los Angeles, CA; 9University of Miami Miller School of Medicine, Miami, FL; 10Kyorin University, Tokyo, Japan
Bruce Sands, MD, MS
Chief, Division of Gastroenterology
Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai
New York, NY, US
Purpose: To evaluate the safety and efficacy of intravenous (IV) ustekinumab (UST) induction therapy in patients with moderately to severely active ulcerative colitis (UC) who demonstrated an inadequate response to or were unable to tolerate conventional (ie, corticosteroids, immunomodulators) or biologic therapies (ie, 1 or more TNF blockers or vedolizumab).
Methods: UNIFI was a Phase 3 randomized, double-blind, placebo-controlled study in which patients were randomized 1:1:1 at Week (Wk) 0 to receive a single IV induction dose of UST 130 mg or a dose approximating UST 6 mg/kg [~6 mg/kg]: 260 mg [weight ≤55 kg], 390 mg [weight >55 kg and <85 kg], or 520 mg [weight >85 kg]) or placebo (PBO). At Wk 8, patients were evaluated for clinical remission, endoscopic healing, clinical response, change from baseline in the IBDQ score, and mucosal healing (an endpoint that includes both endoscopic healing and histologic healing).
Results: Nine hundred sixty-one patients, of which about 50% had failed biologic therapy, were randomized to treatment in the primary analysis population; 941 patients (98%) completed through Wk 8. Baseline demographics, UC disease characteristics and concomitant UC medications were generally similar among treatment groups (Tables 1 and 2). Significantly (p<0.001) higher proportions of patients receiving UST IV 130 mg and ~6 mg/kg achieved clinical remission, endoscopic healing, clinical response, and mucosal healing at Wk 8 and significant improvement from baseline in IBDQ was achieved (Table 3) compared to PBO. Significant (p<0.05) decreases in median levels of fecal biomarkers (calprotectin and lactoferrin) were also observed at Wk 8. Similar proportions of patients reported adverse events (41.4%, 50.0%, and 48.0%), serious adverse events (3.7%, 3.1%, and 6.6%), infections (15.9%, 15.3%, and 15.0%) and serious infections (0.6%, 0.3%, and 1.3%) in the UST IV 130 mg, ~6 mg/kg and PBO groups, respectively. No malignancies, opportunistic infections or tuberculosis were reported through Wk 8. One death from esophageal varices hemorrhage was reported for a patient with no known history of cirrhosis in the UST ~6mg/kg group prior to Wk 8.
Conclusion: A single IV dose of UST resulted in significant improvements in clinical, endoscopic and health-related quality of life outcomes at Wk 8 compared to PBO in patients with moderate-severe UC who had previously failed conventional or biologic therapy. The therapy was well tolerated through induction.
Table 1. Patient characteristics at baseline
Table 2. Concomitant medications for UC at baseline and medication history
Table 3. Primary and other multiplicity-controlled endpoints at Week 8
Bruce E. Sands: Consultant – 4D Pharma, AbbVie, Allergan, Amgen, Arena Pharmaceuticals, Boehringer-Ingelheim, Capella Biosciences, Celltrion Healthcare, EnGene, Ferring, Gilead, Lyndra, Oppilan Pharma, Otsuka, Palatin Technologies, Progenity, Protagonist Therapeutics, Rheos Medicines, Seres Therapeutics, Sienna Biopharmaceuticals, Takeda, Theravance Pharmaceuticals, Vivelix Pharmaceuticals. Advisory Committee/Board Member – Celgene, Janssen, Lilly, MedImmune, Millennium Pharmaceuticals, Pfizer. Grant/Research Support – Janssen, Takeda.
William J. Sandborn: Consultant – Abbvie, Akros Pharma, Allergan, Ambrx Inc., Amgen, Ardelyx, Arena Pharmaceuticals, Atlantic Pharmaceuticals, Avaxia, Biogen, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Conatus, Cosmo Technologies, Escalier Biosciences, Ferring, Ferring Research Institute, Forward Pharma, Galapagos, Genentech, Gilead Sciences, Immune Pharmaceuticals, Index Pharmaceuticals, Janssen, Kyowa Hakko Kirin Pharma, Lilly, Medimmune, Mesoblast, Miraca Life Sciences, Nivalis Therapeutics, Novartis, Nutrition Science Partners, Oppilan Pharma, Otsuka, Palatin, Paul Hastings, Pfizer, Precision IBD, Progenity, Prometheus Laboratories, Qu Biologics, Regeneron, Ritter Pharmaceuticals, Robarts Clinical Trials (owned by Health Academic Research Trust or HART), Salix, Seattle Genetics, Seres Therapeutics, Shire, Sigmoid Biotechnologies, Takeda, Theradiag, Theravance, Tigenix, Tillotts Pharma, UCB Pharma, Vascular Biogenics, Vivelix. Grant/Research Support – Atlantic Healthcare Limited, Amgen, Genentech, Gilead Sciences, Abbvie, Janssen, Takeda, Lilly, Celgene/Receptos. Speakers Bureau – Abbvie, Janssen, Takeda. Stockholder/Ownership Interest (excluding diversified mutual funds) – Escalier Biosciences, Oppilan Pharma, Precision IBD, Progenity, Ritter Pharmaceuticals.
Remo Panaccione: Consultant – AbbVie, Allergan, Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado Biosciences, Eisai Medical Research, Elan, EnGene, Eli Lilly, Ferring, Genentech, Genzyme, Gilead, Given Imaging, GlaxoSmithKline, Human Genome Sciences, Janssen, Merck & Co., Merck Research Laboratories, MerckSerono, Millennium, Novo Nordisk, Pfizer, Procter and Gamble, Prometheus Laboratories, Receptos, Salix, Santarus, Shire Pharmaceuticals, Sigmoid Pharma, Sirtris (a GSK company), Takeda, Therakos, Theradvance, and Tillotts. Advisory Committee/Board Member – Abbvie, Abbott, Allergan, Amgen, Aptalis, AstraZeneca, Baxter, Biogen Idec, Celgene, Eisai, Ferring, Genentech, Janssen, Merck, Shire, Elan, Glaxo-Smith Kline, Hospira, Pfizer, Bristol-Myers Squibb, Takeda, Cubist, Salix. Speakers Bureau – Abbvie, Aptalis, AstraZeneca, Celgene, Ferring, Janssen, Merck, Pfizer, Prometheus, Sandoz, Shire, and Takeda. Grant/Research Support – Abbvie, Ferring, Janssen, Shire, Takeda.
Christopher D. O’Brien: Employee – Janssen Research & Development, LLC.
Hongyan Zhang: Employee – Janssen Research & Development, LLC.
Jewel Johanns: Employee – Janssen Research & Development, LLC.
Laurent Peyrin-Biroulet: Advisory Committee/Board Member – Abbvie, Janssen, Msd, Genentech, Takeda, Celltrion, Biogen, Amgen, Pfizer, Lilly, Tillots, Ferring, Arena, Index. Consultant – Abbvie, Janssen, Msd, Genentech, Takeda, Celltrion, Biogen, Amgen, Pfizer, Lilly, Tillots, Ferring, Arena, Index. Grant/Research Support – Pfizer, Abbvie, Takeda, Merck Sharp Dohme.
Gert van Assche: Consultant – Janssen Research & Development, LLC. Advisory Committee/Board Member – Janssen Research & Development, LLC. Grant/Research Support – Janssen Research & Development, LLC.
Silvio Danese: Speakers Bureau – AbbVie, Allergan, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Hospira, Janssen Johnson & Johnson, Merck, MSD, Takeda, Mundipharma, Pfizer, Sandoz, Tigenix, UCB Pharma, Vifor. Consultant – AbbVie, Allergan, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Hospira, Janssen Johnson & Johnson, Merck, MSD, Takeda, Mundipharma, Pfizer, Sandoz, Tigenix, UCB Pharma, Vifor. Advisory Committee/Board Member – AbbVie, Allergan, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Hospira, Janssen Johnson & Johnson, Merck, MSD, Takeda, Mundipharma, Pfizer, Sandoz, Tigenix, UCB Pharma, Vifor.
Stephan Targan: Consultant – Janssen, Precision IBD Inc. (co-founder). Advisory Committee/Board Member – Symbiotix.
Maria T. Abreu: Consultant – Prometheus Laboratories, Takeda, UCB, Inc., Pfizer, Janssen, Focus Medical Communications, Eli Lilly Pharmaceuticals, Theravance Biopharma Us, Inc. Advisory Committee/Board Member – Abbvie Laboratories, Celgene Corporation, Shire Pharmaceuticals, Roche Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, AMGEN ABP 710 Biosimilar Infliximab, Allergam Brazikumab, SERES, Nestle Health Science, GILEAD. Speakers Bureau – CME Outfitters.
Tadakazu Hisamatsu: Consultant – EA pharma Co. Ltd., AbbVie GK, Celgene K.K., Janssen Pharmaceutical K.K., Pfizer Inc., Nichi-Iko Pharmaceutical Co., Ltd., Pfizer Inc. Grant/Research Support – Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, JIMRO Co. Ltd., Asahi Kasei Kuraray Medical Co, Ltd., Zeria Pharmaceutical Co. Ltd., Daiichi-Sankyo, Kyorin Pharmaceutical Co. Ltd. Nippon Kayaku Co. Ltd., Astellas Pharma Inc., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Mochida Pharmaceutical Co., Ltd. Speakers Bureau – Mitsubishi Tanabe Pharma Corporation, AbbVie GK, EA pharma Co. Ltd., Kyorin Pharmaceutical Co. Ltd., JIMRO Co., Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd.
Philippe Szapary: Employee – Janssen Research & Development, LLC.
Colleen Marano: Employee – Janssen Research & Development, LLC.