Breaking through the therapeutic ceiling of inflammatory bowel disease: Dual-targeted therapies

被引:10
作者
Feng, Zelin [1 ]
Kang, Guangbo [2 ,3 ,4 ,5 ]
Wang, Jiewen [2 ,3 ,4 ,5 ]
Gao, Xingjie [6 ]
Wang, Xiaoli [1 ]
Ye, Yulin [1 ]
Liu, Limin [1 ]
Zhao, Jingwen [1 ]
Liu, Xinjuan [7 ]
Huang, He [2 ,3 ,4 ]
Cao, Xiaocang [1 ]
机构
[1] Tianjin Med Univ Gen Hosp, Tianjin Inst Digest Dis, Dept Gastroenterol & Hepatol, Tianjin Key Lab Digest Dis, Tianjin 300052, Peoples R China
[2] Tianjin Univ, Sch Chem Engn & Technol, Dept Biochem Engn, Tianjin 300350, Peoples R China
[3] Tianjin Univ, Frontiers Sci Ctr Synthet Biol, Minist Educ, Tianjin 300072, Peoples R China
[4] Tianjin Univ, Key Lab Syst Bioengn, Minist Educ, Tianjin 300072, Peoples R China
[5] Tianjin Univ, Inst Shaoxing, Shaoxing 312300, Zhejiang, Peoples R China
[6] Tianjin Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Tianjin 300070, Peoples R China
[7] Capital Med Univ, Beijing Chaoyang Hosp, Dept Gastroenterol, Beijing 100016, Peoples R China
基金
中国国家自然科学基金;
关键词
Inflammatory bowel diseases; Dual-targeted therapy; Janus kinases pathway; Tumor necrosis factor-alpha; Leukocyte trafficking; SEVERE CROHNS-DISEASE; ANTITUMOR NECROSIS FACTOR; JAK-STAT PATHWAY; ANTI-TNF-ALPHA; MAINTENANCE THERAPY; ULCERATIVE-COLITIS; COMBINATION THERAPY; MONOCLONAL-ANTIBODY; DOUBLE-BLIND; OZANIMOD INDUCTION;
D O I
10.1016/j.biopha.2022.114174
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Emerging biologics and small-molecule drugs have changed the clinical status quo of inflammatory bowel disease (IBD). However, current treatments remain at a standstill in terms of response and remission in many cases. Accumulating evidence indicates that dual-targeted therapy (DTT) could be promising in overcoming the existing ceiling of IBD treatment. However, data on the efficacy and safety of DTT on Crohn's disease and ulcerative colitis are still limited or insufficient. Moreover, there is a lack of studies delineating the mechanisms of DTT. Given that various targeted drugs have different targets among the extensive redundant inflammatory networks, DTT could result in various outcomes. In this review, we have summarized the current data on the safety, effectiveness, and clinical development status of novel targeted drugs related to refractory IBD, and have explored the mechanism of action of therapy. We have categorized therapeutic agents into "Therapeutic Agents Targeting Cellular Signaling Pathways" and "Therapeutic Agents Targeting Leukocyte Trafficking" based on the different therapeutic targets, and also by classifying therapeutic agents targeting the cellular signaling pathways into "JAK-dependent" and "JAK-independent," and placed the existing drug combinations into 3 categories based on their mechanisms, namely, overlapping, synergistic, and complementary effects. Lastly, we have proposed the possible mechanisms of DTT to conceive a theoretical framework for clinical decision-making and further drug development and research from an IBD standpoint.
引用
收藏
页数:18
相关论文
共 143 条
  • [81] Combination of Biological Agents in Moderate to Severe Pediatric Inflammatory Bowel Disease: A Case Series and Review of the Literature
    Olbjorn, Christine
    Rove, Jon Bergreen
    Jahnsen, Jorgen
    [J]. PEDIATRIC DRUGS, 2020, 22 (04) : 409 - 416
  • [82] Mechanisms behind efficacy of tumor necrosis factor inhibitors in inflammatory bowel diseases
    Olesen, Caroline Meyer
    Coskun, Mehmet
    Peyrin-Biroulet, Laurent
    Nielsen, Ole Haagen
    [J]. PHARMACOLOGY & THERAPEUTICS, 2016, 159 : 110 - 119
  • [83] The use of combination biologic therapy in inflammatory bowel disease: A single tertiary-centre experience
    Panaccione, N.
    Novak, K.
    Seow, C.
    Devlin, S.
    Lu, C.
    Heatherington, J.
    Martin, M. -L.
    Kaplan, G.
    Panaccione, R.
    [J]. JOURNAL OF CROHNS & COLITIS, 2019, 13 : S480 - S480
  • [84] Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials
    Panes, Julian
    Sandborn, William J.
    Schreiber, Stefan
    Sands, Bruce E.
    Vermeire, Severine
    D'Haens, Geert
    Panaccione, Remo
    Higgins, Peter D. R.
    Colombel, Jean-Frederic
    Feagan, Brian G.
    Chan, Gary
    Moscariello, Michele
    Wang, Wenjin
    Niezychowski, Wojciech
    Marren, Amy
    Healey, Paul
    Maller, Eric
    [J]. GUT, 2017, 66 (06) : 1049 - 1059
  • [85] Therapeutic drug monitoring of biologics in inflammatory bowel disease: unmet needs and future perspectives
    Papamichael, Konstantinos
    Afif, Waqqas
    Drobne, David
    Dubinsky, Marla C.
    Ferrante, Marc
    Irving, Peter M.
    Kamperidis, Nikolaos
    Kobayashi, Taku
    Kotze, Paulo G.
    Lambert, Jo
    Noor, Nurulamin M.
    Roblin, Xavier
    Roda, Giulia
    Vande Casteele, Niels
    Yarur, Andres J.
    Arebi, Naila
    Danese, Silvio
    Paul, Stephane
    Sandborn, William J.
    Vermeire, Severine
    Cheifetz, Adam S.
    Peyrin-Biroulet, Laurent
    Monitoring, International Consortium for Therapeutic Drug
    [J]. LANCET GASTROENTEROLOGY & HEPATOLOGY, 2022, 7 (02): : 171 - 185
  • [86] Therapeutic drug monitoring with biologic agents in immune mediated inflammatory diseases
    Papamichael, Konstantinos
    Vogelzang, Erik
    Lambert, Jo
    Wolbink, Gertjan
    Cheifetz, Adam S.
    [J]. EXPERT REVIEW OF CLINICAL IMMUNOLOGY, 2019, 15 (08) : 837 - 848
  • [87] A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rβ1 and a novel cytokine receptor subunit, IL-23R
    Parham, C
    Chirica, M
    Timans, J
    Vaisberg, E
    Travis, M
    Cheung, J
    Pflanz, S
    Zhang, R
    Singh, KP
    Vega, F
    To, W
    Wagner, J
    O'Farrell, AM
    McClanahan, T
    Zurawski, S
    Hannum, C
    Gorman, D
    Rennick, DM
    Kastelein, RA
    Malefyt, RD
    Moore, KW
    [J]. JOURNAL OF IMMUNOLOGY, 2002, 168 (11) : 5699 - 5708
  • [88] Review article: remission rates achievable by current therapies for inflammatory bowel disease
    Peyrin-Biroulet, L.
    Lemann, M.
    [J]. ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2011, 33 (08) : 870 - 879
  • [89] Bispecific antibodies: The next generation of targeted inflammatory bowel disease therapies
    Peyrin-Biroulet, Laurent
    Demarest, Stephen
    Nirula, Ajay
    [J]. AUTOIMMUNITY REVIEWS, 2019, 18 (02) : 123 - 128
  • [90] Privitera Giuseppe, 2021, Therap Adv Gastroenterol, V14, p17562848211006669, DOI 10.1177/17562848211006669