Silvio Danese, MD, PhD1, William J. Sandborn, MD, FACG2, Walter Reinisch, MD3, Xavier Hébuterne, MD4, Maria Kłopocka, MD, PhD5, Dino Tarabar, MD, PhD6, Tomáš Vaňásek, MD, PhD7, Miloš Greguš, MD8, Paul A. Hellstern, MD9, Joo Sung Kim, PhD, MD, MS10, Miles Sparrow, MD, PhD, MBBS11, Kenneth J. Gorelick, MD12, Martina Goetsch, MD13, Caleb Bliss, PhD14, Charu Gupta, MS15, Fabio Cataldi, MD14, Séverine Vermeire, MD, PhD16
1Humanitas University, Milan, Lombardia, Italy; 2University of California San Diego, La Jolla, CA; 3Medical University of Vienna, Vienna, Wien, Austria; 4Université de Nice-Sophia-Antipolis, Nice, Provence-Alpes-Cote d'Azur, France; 5Nicolaus Copernicus University, Collegium Medicum, Bydgoszcz, Kujawsko-Pomorskie, Poland; 6Military Medical Academy, Belgrade, Vojvodina, Serbia; 7Charles University Hospital, Hradec Králové, Kralovehradecky kraj, Czech Republic; 8Gastroenterology Center, Nitra, Nitra, Slovakia; 9Nature Coast Clinical Research, Inverness, FL; 10Seoul National University College of Medicine, Seoul, Seoul-t'ukpyolsi, Republic of Korea; 11Alfred Hospital, Melbourne, Victoria, Australia; 12Zymo Consulting Group, Newtown Square, PA; 13Shire, a Takeda company, Zug, Zug, Switzerland; 14Shire, a Takeda company, Lexington, MA; 15Cytel Inc., Cambridge, MA; 16University Hospitals, Leuven, Vlaams-Brabant, Belgium
Introduction: Ontamalimab (SHP647), a human monoclonal IgG2 antibody, targets mucosal addressin cell adhesion molecule-1 (MAdCAM-1), to reduce lymphocyte homing to the gastrointestinal (GI) tract. In the TURANDOT II trial, ontamalimab was well-tolerated and clinical benefit was seen up to 144 wks in patients with ulcerative colitis (UC). Here we report long-term mucosal healing, response and remission in a subset of patients in TURANDOT II.
Methods: TURANDOT II (NCT01771809) is a phase 2, 2-part open-label (OL) extension study of ontamalimab in patients with UC who received placebo or ontamalimab 7.5, 22.5, 75 or 225mg in the feeder study (TURANDOT). At TURANDOT II baseline (TURANDOT wk 12), patients were randomized to ontamalimab 75 or 225mg every 4 wks for 72 wks (OL1). In cases of clinical exacerbation or no response, escalation from 75 to 225mg was permitted from wk 8. In OL2, patients received 75mg every 4 wks for 72 wks. Endoscopies were carried out at wk 16, and a subset of patients undergoing routine cancer surveillance had at least one follow-up endoscopy between wks 40 and 72 of OL1: all endoscopies were centrally-read. Mucosal healing (Mayo endoscopy subscore ≤1), clinical remission (total Mayo score ≤2, no subscore >1) and clinical response (≥3-point decrease in total Mayo score from TURANDOT baseline, ≥30% change; ≥1-point decrease in or ≤1 rectal bleed absolute score) were measured.
Results: Of 330 patients in TURANDOT II, 101 had follow-up endoscopies (Table 1), 25.7% (n=26) of whom had mucosal healing at TURANDOT II baseline. At wk 16, 43.6% (n=44) had mucosal healing, and 33 of these patients (75%) maintained mucosal healing up to wk 40–72. Of 65 responders in TURANDOT, 37 (56.9%) had mucosal healing at both wk 16 and wk 40–72. Of 36 non-responders, 7 (19.4%) and 9 (25%) achieved mucosal healing at wk 16 and wk 40–72, respectively (Figure 1). Of the responders, 58 (89.2%) maintained response and 27 (41.5%) were in remission at wk 16; at wk 40–72, 53 (81.5%) maintained response and 33 (50.8%) were in remission. Of non-responders, 22 (61.1%) achieved response and 5 (13.9%) achieved remission by wk 16; by wk 40–72, 17 (47.2%) had responded and 8 (22.2%) were in remission. Overall, the mean Mayo endoscopic subscore of 2 (SD, 0.1) was maintained to wk 40–72.
Discussion: Mucosal healing, response and remission persisted in a subset of patients who continued ontamalimab treatment up to 72 wks and underwent surveillance endoscopies between wks 40 and 72.
Citation: Silvio Danese, MD, PhD; William J. Sandborn, MD, FACG; Walter Reinisch, MD; Xavier Hébuterne, MD; Maria Kłopocka, MD, PhD; Dino Tarabar, MD, PhD; Tomáš Vaňásek, MD, PhD; Miloš Greguš, MD; Paul A. Hellstern, MD; Joo Sung Kim, PhD, MD, MS; Miles Sparrow, MD, PhD, MBBS; Kenneth J. Gorelick, MD; Martina Goetsch, MD; Caleb Bliss, PhD; Charu Gupta, MS; Fabio Cataldi, MD; Séverine Vermeire, MD, PhD. P1417 - LONG-TERM MUCOSAL HEALING, CLINICAL RESPONSE AND CLINICAL REMISSION IN PATIENTS WITH ULCERATIVE COLITIS TREATED WITH THE ANTI-MADCAM-1 ANTIBODY ONTAMALIMAB: RESULTS FROM THE OPEN-LABEL EXTENSION STUDY TURANDOT II. Program No. P1417. ACG 2019 Annual Scientific Meeting Abstracts. San Antonio, Texas: American College of Gastroenterology.