Emerging drugs for the treatment of moderately to severely active ulcerative colitis: review of phase II and III clinical trials

被引:5
作者
Neurath, Laura [1 ,2 ]
D'Amico, Ferdinando [1 ,2 ,3 ]
Danese, Silvio [1 ,2 ,4 ,5 ]
机构
[1] IRCCS Osped San Raffaele, Gastroenterol & Endoscopy, Milan, Italy
[2] Univ Vita Salute San Raffaele, Milan, Italy
[3] Humanitas Univ, Dept Biomed Sci, Pieve Emanuele, Italy
[4] IRCCS Osped San Raffaele, Gastroenterol & Endoscopy, Via Olgettina 60, Milan, Italy
[5] Univ Vita Salute San Raffaele, Via Olgettina 60, Milan, Italy
关键词
Inflammatory bowel disease; ulcerative colitis; treatment; phase II and phase III trials; INFLAMMATORY-BOWEL-DISEASE; JANUS KINASE INHIBITOR; TO-SEVERE; MAINTENANCE THERAPY; CROHNS-DISEASE; DOUBLE-BLIND; BIOLOGICAL THERAPY; INDUCTION THERAPY; ANTI-TNF; VEDOLIZUMAB;
D O I
10.1080/14728214.2023.2186399
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
IntroductionCurrent therapeutic options for patients with ulcerative colitis comprise monoclonal antibodies against tumor necrosis factor (TNF), alpha4/beta7 integrin, and interleukin (IL)12/23 as well as small molecules such as tofacitinib, upadacitinib, ozanimod, and filgotinib. However, many patients fail to respond to these agents or have loss of response over time. Therefore, there is a large unmet clinical need for new therapeutic agents.Areas coveredHere, we review recent phase 2/3 studies in active ulcerative colitis and discuss preliminary data on the efficacy (clinical, endoscopic, and histologic remission) and safety of novel drugs including Janus kinase (JAK) inhibitors, IL23 blockers, integrin inhibitors, and S1P1R modulators.Expert opinionWe highlight the potential impact of these agents for the future therapeutic landscape of this disease with special emphasis on clinical impact, unmet needs, safety aspects, and advanced combination therapy.
引用
收藏
页码:27 / 42
页数:16
相关论文
共 98 条
[1]   Safety Profile of IBD Therapeutics: Infectious Risks (Reprinted from Gastroenterology Clinics of North America, vol 38) [J].
Afif, Waqqas ;
Loftus, Edward V., Jr. .
MEDICAL CLINICS OF NORTH AMERICA, 2010, 94 (01) :115-+
[2]   Patient Perspectives and Expectations in Inflammatory Bowel Disease: A Systematic Review [J].
Al Khoury, Alex ;
Balram, Bhairavi ;
Bessissow, Talat ;
Afif, Waqqas ;
Gonczi, Lorant ;
Abreu, Maria ;
Lakatos, Peter L. .
DIGESTIVE DISEASES AND SCIENCES, 2022, 67 (06) :1956-1974
[3]   The market for ulcerative colitis [J].
Al-Horani, Rami ;
Spanudakis, Eleonora ;
Hamad, Bashar .
NATURE REVIEWS DRUG DISCOVERY, 2022, 21 (01) :15-16
[4]   Environmental triggers in IBD: a review of progress and evidence [J].
Ananthakrishnan, Ashwin N. ;
Bernstein, Charles N. ;
Iliopoulos, Dimitrios ;
Macpherson, Andrew ;
Neurath, Markus F. ;
Ali, Raja A. Raja ;
Vavricka, Stephan R. ;
Fiocchi, Claudio .
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2018, 15 (01) :39-49
[5]   Cobitolimod for moderate-to-severe, left-sided ulcerative colitis (CONDUCT): a phase 2b randomised, double-blind, placebo-controlled, dose-ranging induction trial [J].
Atreya, Raja ;
Peyrin-Biroulet, Laurent ;
Klymenko, Andrii ;
Augustyn, Monica ;
Bakulin, Igor ;
Slankamenac, Dusan ;
Miheller, Pal ;
Gasbarrini, Antonio ;
Hebuterne, Xavier ;
Arnesson, Karin ;
Knittel, Thomas ;
Kowalski, Jan ;
Neurath, Markus F. ;
Sandborn, William J. ;
Reinisch, Walter .
LANCET GASTROENTEROLOGY & HEPATOLOGY, 2020, 5 (12) :1063-1075
[6]   Vedolizumab as the first line of biologic therapy for ulcerative colitis and Crohn's disease - a systematic review with meta-analysis [J].
Attauabi, Mohamed ;
Madsen, Gorm Roager ;
Bendtsen, Flemming ;
Seidelin, Jakob Benedict ;
Burisch, Johan .
DIGESTIVE AND LIVER DISEASE, 2022, 54 (09) :1168-1178
[7]   Vedolizumab as first-line biological therapy in elderly patients and those with contraindications for anti-TNF therapy: a real-world, nationwide cohort of patients with inflammatory bowel diseases [J].
Attauabi, Mohamed ;
Hoglund, Camilla ;
Fassov, Janne ;
Pedersen, Kenneth Bo ;
Hansen, Heidi Bansholm ;
Wildt, Signe ;
Jensen, Michael Dam ;
Neumann, Anders ;
Lind, Cecilie ;
Jacobsen, Henrik Albaek ;
Popa, Ana-Maria ;
Kjeldsen, Jens ;
Pedersen, Natalia ;
Molazahi, Akbar ;
Haderslev, Kent ;
Aalykke, Claus ;
Knudsen, Torben ;
Cebula, Wojciech ;
Munkholm, Pia ;
Bendtsen, Flemming ;
Seidelin, Jakob Benedict ;
Burisch, Johan .
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 2021, 56 (09) :1040-1048
[8]   Safety of JAK inhibitors: focus on cardiovascular and thromboembolic events [J].
Atzeni, Fabiola ;
Popa, Calin D. ;
Nucera, Valeria ;
Nurmohamed, Michael T. .
EXPERT REVIEW OF CLINICAL IMMUNOLOGY, 2022, 18 (03) :233-244
[9]   Mucosal Healing Predicts Sustained Clinical Remission in Patients With Early-Stage Crohn's Disease [J].
Baert, Filip ;
Moortgat, Liesbeth ;
Van Assche, Gert ;
Caenepeel, Philip ;
Vergauwe, Philippe ;
De Vos, Martine ;
Stokkers, Pieter ;
Hommes, Daniel ;
Rutgeerts, Paul ;
Vermeire, Severine ;
D'Haens, Geert .
GASTROENTEROLOGY, 2010, 138 (02) :463-468
[10]   Review article: predictors of response to vedolizumab and ustekinumab in inflammatory bowel disease [J].
Barre, A. ;
Colombel, J. -F. ;
Ungaro, R. .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2018, 47 (07) :896-905