Investigational drugs in phase I and phase II clinical trials targeting interleukin 23 (IL23) for the treatment of Crohn’s disease

References

• Baumgart DC, Sandborn WJ. Crohn’s disease. Lancet. 2012 Nov 3;380(9853):1590–1605. . PubMed PMID: 22914295.
   PubMed Web of Science ®Google Scholar
• Lonnfors S, Vermeire S, Greco M, et al. IBD and health-related quality of life – discovering the true impact. J Crohns Colitis. 2014 Oct;8(10):1281–1286. PubMed PMID: 24662394.
   PubMed Web of Science ®Google Scholar
• Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017;390(10114):2769–2778. PubMed PMID: 29050646.
   PubMed Web of Science ®Google Scholar
• Sartor RB. Mechanisms of disease: pathogenesis of Crohn’s disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol. 2006 Jul;3(7):390–407. . PubMed PMID: 16819502.
   PubMedGoogle Scholar
• de Souza HS, Fiocchi C. Immunopathogenesis of IBD: current state of the art. Nat Rev Gastroenterol Hepatol. 2016 Jan;13(1):13–27. . PubMed PMID: 26627550.
   PubMed Web of Science ®Google Scholar
• Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol. 2015 Sep;110(9):1324–1338. PubMed PMID: 26303131.
   PubMed Web of Science ®Google Scholar
• Duijvestein M, Battat R, Vande Casteele N, et al. Novel therapies and treatment strategies for patients with inflammatory bowel disease. Curr Treat Options Gastroenterol. 2018 Mar;16(1):129–146. 10.1007/s11938-018-0175-1. PubMed PMID: 29411220.
   PubMedGoogle Scholar
• Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002 May 4;359(9317):1541–1549. PubMed PMID: 12047962.
   PubMed Web of Science ®Google Scholar
• Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004 Feb 26;350(9):876–885. PubMed PMID: 14985485.
   PubMed Web of Science ®Google Scholar
• Targan SR, Hanauer SB, van Deventer SJ, et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. Crohn’s Disease cA2 Study Group. N Engl J Med. 1997 Oct 9;337(15):1029–1035. PubMed PMID: 9321530.
   PubMed Web of Science ®Google Scholar
• Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology. 2007 Jan;132(1):52–65. PubMed PMID: 17241859.
   PubMed Web of Science ®Google Scholar
• Hanauer SB, Sandborn WJ, Rutgeerts P, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I trial. Gastroenterology. 2006 Feb;130(2):323–33; quiz 591. PubMed PMID: 16472588.
   PubMed Web of Science ®Google Scholar
• Sandborn WJ, Feagan BG, Stoinov S, et al. Certolizumab pegol for the treatment of Crohn’s disease. N Engl J Med. 2007 Jul 19;357(3):228–238. PubMed PMID: 17634458.
   PubMed Web of Science ®Google Scholar
• Schreiber S, Khaliq-Kareemi M, Lawrance IC, et al. Maintenance therapy with certolizumab pegol for Crohn’s disease. N Engl J Med. 2007 Jul 19;357(3):239–250. PubMed PMID: 17634459.
   PubMed Web of Science ®Google Scholar
• Roda G, Jharap B, Neeraj N, et al. Loss of response to anti-TNFs: definition, epidemiology, and management. Clin Transl Gastroenterol. 2016 Jan 7;7:e135. PubMed PMID: 26741065; PubMed Central PMCID: PMCPMC4737871.
   PubMed Web of Science ®Google Scholar
• Danese S, Fiorino G, Reinisch W. Review article: causative factors and the clinical management of patients with Crohn’s disease who lose response to anti-TNF-alpha therapy. Aliment Pharmacol Ther. 2011 Jul;34(1):1–10. . PubMed PMID: 21539588.
   PubMed Web of Science ®Google Scholar
• Gisbert JP, Marin AC, McNicholl AG, et al. Systematic review with meta-analysis: the efficacy of a second anti-TNF in patients with inflammatory bowel disease whose previous anti-TNF treatment has failed. Aliment Pharmacol Ther. 2015 Apr;41(7):613–623. PubMed PMID: 25652884.
   PubMed Web of Science ®Google Scholar
• Jairath V, Levesque BG, Vande Casteele N, et al. Evolving concepts in phases I and II drug development for Crohn’s disease. J Crohns Colitis. 2017 Feb;11(2):246–255. PubMed PMID: 27487793.
   PubMed Web of Science ®Google Scholar
• Iwakura Y, Ishigame H. The IL-23/IL-17 axis in inflammation. J Clin Invest. 2006 May;116(5):1218–1222. . PubMed PMID: 16670765; PubMed Central PMCID: PMCPMC1451213.
   PubMed Web of Science ®Google Scholar
• Yen D, Cheung J, Scheerens H, et al. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest. 2006 May;116(5):1310–1316. PubMed PMID: 16670770; PubMed Central PMCID: PMCPMC1451201.
   PubMed Web of Science ®Google Scholar
• Duerr RH, Taylor KD, Brant SR, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006 Dec 1;314(5804):1461–1463. PubMed PMID: 17068223; PubMed Central PMCID: PMCPMC4410764.
   PubMed Web of Science ®Google Scholar
• Feagan BG, Sandborn WJ, Gasink C, et al. Ustekinumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2016 Nov 17;375(20):1946–1960. PubMed PMID: 27959607.
   PubMed Web of Science ®Google Scholar
• Kotze PG, Ma C, Almutairdi A, et al. Clinical utility of ustekinumab in Crohn’s disease. J Inflamm Res. 2018;11:35–47. PubMed PMID: 29445293; PubMed Central PMCID: PMCPMC5810512.
   PubMed Web of Science ®Google Scholar
• Ma C, Fedorak RN, Kaplan GG, et al. Clinical, endoscopic and radiographic outcomes with ustekinumab in medically-refractory Crohn’s disease: real world experience from a multicentre cohort. Aliment Pharmacol Ther. 2017 May;45(9):1232–1243. PubMed PMID: 28252210.
   PubMed Web of Science ®Google Scholar
• Sandborn W, Gasink C, Chan D, et al. Endoscopic healing in the ustekinumab phase 3 UNITI/IMUNITI Crohn’s disease program and relationship of clinical outcomes to baseline ulceration status. Inflamm Bowel Dis. 2017;23(Suppl_1):PD–012.
   Google Scholar
• Bowman EP, Chackerian AA, Cua DJ. Rationale and safety of anti-interleukin-23 and anti-interleukin-17A therapy. Curr Opin Infect Dis. 2006 Jun;19(3):245–252. . PubMed PMID: 16645485.
   PubMed Web of Science ®Google Scholar
• Fieschi C, Casanova JL. The role of interleukin-12 in human infectious diseases: only a faint signature. Eur J Immunol. 2003 Jun;33(6):1461–1464. . PubMed PMID: 12778462.
   PubMed Web of Science ®Google Scholar
• Meeran SM, Mantena SK, Meleth S, et al. Interleukin-12-deficient mice are at greater risk of UV radiation-induced skin tumors and malignant transformation of papillomas to carcinomas. Mol Cancer Ther. 2006 Apr;5(4):825–832. PubMed PMID: 16648552.
   PubMed Web of Science ®Google Scholar
• Papp K, Gottlieb AB, Naldi L, et al. Safety surveillance for ustekinumab and other psoriasis treatments from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). J Drugs Dermatol. 2015 Jul;14(7):706–714. PubMed PMID: 26151787.
   PubMed Web of Science ®Google Scholar
• Griffiths CE, Strober BE, van de Kerkhof P, et al. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med. 2010 Jan 14;362(2):118–128. PubMed PMID: 20071701.
   PubMed Web of Science ®Google Scholar
• Reich K, Pinter A, Lacour JP, et al. Comparison of ixekizumab with ustekinumab in moderate-to-severe psoriasis: 24-week results from IXORA-S, a phase III study. Br J Dermatol. 2017 Oct;177(4):1014–1023. PubMed PMID: 28542874.
   PubMed Web of Science ®Google Scholar
• Lebwohl M, Strober B, Menter A, et al. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N Engl J Med. 2015 Oct;373(14):1318–1328. PubMed PMID: 26422722.
   PubMed Web of Science ®Google Scholar
• Langley RG, Tsai TF, Flavin S, et al. Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double-blind, phase III NAVIGATE trial. Br J Dermatol. 2018 Jan;178(1):114–123. PubMed PMID: 28635018.
   PubMed Web of Science ®Google Scholar
• Papp KA, Blauvelt A, Bukhalo M, et al. Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis. N Engl J Med. 2017 Apr 20;376(16):1551–1560. PubMed PMID: 28423301.
   PubMed Web of Science ®Google Scholar
• Feagan BG, Sandborn WJ, D’Haens G, et al. Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn’s disease: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. 2017 Apr 29;389(10080):1699–1709. PubMed PMID: 28411872.
   PubMed Web of Science ®Google Scholar
• Sands BE, Chen J, Feagan BG, et al. Efficacy and safety of MEDI2070, an antibody against interleukin 23, in patients with moderate to severe Crohn’s disease: a phase 2a study. Gastroenterology. 2017 Jul;153(1):77–86 e6. PubMed PMID: 28390867.
   PubMed Web of Science ®Google Scholar
• Deepak P, Sandborn WJ. Ustekinumab and anti-interleukin-23 agents in Crohn’s disease. Gastroenterol Clin North Am. 2017 Sep;46(3):603–626. . PubMed PMID: 28838418.
   PubMed Web of Science ®Google Scholar
• Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations. Annu Rev Immunol. 2010;28:445–489. PubMed PMID: 20192806; PubMed Central PMCID: PMCPMC3502616.
   PubMed Web of Science ®Google Scholar
• Huang Y, Chen Z. Inflammatory bowel disease related innate immunity and adaptive immunity. Am J Transl Res. 2016;8(6): 2490–2497. PubMed PMID: 27398134; PubMed Central PMCID: PMCPMC4931145.
   PubMed Web of Science ®Google Scholar
• Gee K, Guzzo C, Che Mat NF, et al. The IL-12 family of cytokines in infection, inflammation and autoimmune disorders. Inflamm Allergy Drug Targets. 2009 Mar;8(1):40–52. PubMed PMID: 19275692.
   PubMedGoogle Scholar
• Oppmann B, Lesley R, Blom B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 2000 Nov;13(5):715–725. PubMed PMID: 11114383.
   PubMed Web of Science ®Google Scholar
• Parham C, Chirica M, Timans J, et al. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J Immunol. 2002 Jun 1;168(11):5699–5708. PubMed PMID: 12023369.
   PubMed Web of Science ®Google Scholar
• Abraham C, Dulai PS, Vermeire S, et al. Lessons learned from trials targeting cytokine pathways in patients with inflammatory bowel diseases. Gastroenterology. 2017 Feb;152(2):374–388 e4. PubMed PMID: 27780712; PubMed Central PMCID: PMCPMC5287922.
   PubMed Web of Science ®Google Scholar
• van de Wetering D, De Paus RA, van Dissel JT, et al. IL-23 modulates CD56+/CD3- NK cell and CD56+/CD3+ NK-like T cell function differentially from IL-12. Int Immunol. 2009 Feb;21(2):145–153. PubMed PMID: 19088061.
   PubMed Web of Science ®Google Scholar
• Geremia A, Arancibia-Carcamo CV, Fleming MP, et al. IL-23-responsive innate lymphoid cells are increased in inflammatory bowel disease. J Exp Med. 2011 Jun 6;208(6):1127–1133. PubMed PMID: 21576383; PubMed Central PMCID: PMCPMC3173242.
   PubMed Web of Science ®Google Scholar
• Kvedaraite E, Lourda M, Idestrom M, et al. Tissue-infiltrating neutrophils represent the main source of IL-23 in the colon of patients with IBD. Gut. 2016 Oct;65(10):1632–1641. PubMed PMID: 26160381.
   PubMed Web of Science ®Google Scholar
• Bouma G, Strober W. The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol. 2003 Jul;3(7):521–533. PubMed PMID: 12876555.
   PubMed Web of Science ®Google Scholar
• Becker C, Wirtz S, Blessing M, et al. Constitutive p40 promoter activation and IL-23 production in the terminal ileum mediated by dendritic cells. J Clin Invest. 2003 Sep;112(5):693–706. PubMed PMID: 12952918; PubMed Central PMCID: PMCPMC182190.
   PubMed Web of Science ®Google Scholar
• Wiekowski MT, Leach MW, Evans EW, et al. Ubiquitous transgenic expression of the IL-23 subunit p19 induces multiorgan inflammation, runting, infertility, and premature death. J Immunol. 2001 Jun 15;166(12):7563–7570. PubMed PMID: 11390512.
   PubMed Web of Science ®Google Scholar
• Hue S, Ahern P, Buonocore S, et al. Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J Exp Med. 2006 Oct 30;203(11):2473–2483. PubMed PMID: 17030949; PubMed Central PMCID: PMCPMC2118132.
   PubMed Web of Science ®Google Scholar
• Geremia A, Arancibia-Carcamo CV. Innate lymphoid cells in intestinal inflammation. Front Immunol. 2017;8:1296. PubMed PMID: 29081776; PubMed Central PMCID: PMCPMC5645495.
   PubMed Web of Science ®Google Scholar
• Buonocore S, Ahern PP, Uhlig HH, et al. Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology. Nature. 2010 Apr 29;464(7293):1371–1375. PubMed PMID: 20393462; PubMed Central PMCID: PMCPMC3796764.
   PubMed Web of Science ®Google Scholar
• Pearson C, Thornton EE, McKenzie B, et al. ILC3 GM-CSF production and mobilisation orchestrate acute intestinal inflammation. Elife. 2016 Jan 18;5:e10066. PubMed PMID: 26780670; PubMed Central PMCID: PMCPMC4733039.
   PubMed Web of Science ®Google Scholar
• Fuchs A, Vermi W, Lee JS, et al. Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15-responsive IFN-gamma-producing cells. Immunity. 2013 Apr 18;38(4):769–781. PubMed PMID: 23453631; PubMed Central PMCID: PMCPMC3634355.
   PubMed Web of Science ®Google Scholar
• Qiu J, Heller JJ, Guo X, et al. The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. Immunity. 2012 Jan 27;36(1):92–104. PubMed PMID: 22177117; PubMed Central PMCID: PMCPMC3268875.
   PubMed Web of Science ®Google Scholar
• Zhou L, Ivanov II, Spolski R, et al. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol. 2007 Sep;8(9):967–974. PubMed PMID: 17581537.
   PubMed Web of Science ®Google Scholar
• Huh JR, Littman DR. Small molecule inhibitors of rorgammat: targeting Th17 cells and other applications. Eur J Immunol. 2012 Sep;42(9):2232–2237. . PubMed PMID: 22949321; PubMed Central PMCID: PMCPMC3609417.
   PubMed Web of Science ®Google Scholar
• Withers DR, Hepworth MR, Wang X, et al. Transient inhibition of ROR-gammat therapeutically limits intestinal inflammation by reducing TH17 cells and preserving group 3 innate lymphoid cells. Nat Med. 2016 Mar;22(3):319–323. PubMed PMID: 26878233; PubMed Central PMCID: PMCPMC4948756.
   PubMed Web of Science ®Google Scholar
• Hueber W, Sands BE, Lewitzky S, et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut. 2012 Dec;61(12):1693–1700. PubMed PMID: 22595313; PubMed Central PMCID: PMCPMC4902107.
   PubMed Web of Science ®Google Scholar
• O’Connor W Jr., Kamanaka M, Booth CJ, et al. A protective function for interleukin 17A in T cell-mediated intestinal inflammation. Nat Immunol. 2009 Jun;10(6):603–609. PubMed PMID: 19448631; PubMed Central PMCID: PMCPMC2709990.
   PubMed Web of Science ®Google Scholar
• Sugimoto K, Ogawa A, Mizoguchi E, et al. IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. J Clin Invest. 2008 Feb;118(2):534–544. PubMed PMID: 18172556; PubMed Central PMCID: PMCPMC2157567.
   PubMed Web of Science ®Google Scholar
• Cox JH, Kljavin NM, Ota N, et al. Opposing consequences of IL-23 signaling mediated by innate and adaptive cells in chemically induced colitis in mice. Mucosal Immunol. 2012 Jan;5(1):99–109. PubMed PMID: 22089030.
   PubMed Web of Science ®Google Scholar
• Eken A, Singh AK, Oukka M. Interleukin 23 in Crohn’s disease. Inflamm Bowel Dis. 2014 Mar;20(3):587–595. . PubMed PMID: 24481050; PubMed Central PMCID: PMCPMC3966024.
   PubMed Web of Science ®Google Scholar
• Siakavellas SI, Bamias G. Role of the IL-23/IL-17 axis in Crohn’s disease. Discov Med. 2012 Oct;14(77):253–262. PubMed PMID: 23114581.
   PubMed Web of Science ®Google Scholar
• Singh S, Kroe-Barrett RR, Canada KA, et al. Selective targeting of the IL23 pathway: generation and characterization of a novel high-affinity humanized anti-IL23A antibody. MAbs. 2015;7(4):778–791. PubMed PMID: 25905918; PubMed Central PMCID: PMCPMC4622456.
   PubMed Web of Science ®Google Scholar
• Krueger JG, Ferris LK, Menter A, et al. Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol. 2015 Jul;136(1):116–124 e7. PubMed PMID: 25769911.
   PubMed Web of Science ®Google Scholar
• Feagan BG, Panes J, Ferrante M, et al. Efficacy and safety of open-label maintenance therapy with subcutaneous risankizumab in patients with moderate-to-severe Crohn’s disease. Gastroenterology. 2017;152(5):S1310.
   PubMed Web of Science ®Google Scholar
• Kock K, Pan WJ, Gow JM, et al. Preclinical development of AMG 139, a human antibody specifically targeting IL-23. Br J Pharmacol. 2015 Jan;172(1):159–172. PubMed PMID: 25205227; PubMed Central PMCID: PMCPMC4280975.
   PubMed Web of Science ®Google Scholar
• Markham A. Guselkumab: first global approval. Drugs. 2017 Sep;77(13):1487–1492. 10.1007/s40265-017-0800-7. PubMed PMID: 28819723.
   PubMed Web of Science ®Google Scholar
• Zhuang Y, Calderon C, Marciniak SJ Jr., et al. First-in-human study to assess guselkumab (anti-IL-23 mAb) pharmacokinetics/safety in healthy subjects and patients with moderate-to-severe psoriasis. Eur J Clin Pharmacol. 2016 Nov;72(11):1303–1310. 10.1007/s00228-016-2110-5. PubMed PMID: 27515978.
   PubMed Web of Science ®Google Scholar
• Kopp T, Riedl E, Bangert C, et al. Clinical improvement in psoriasis with specific targeting of interleukin-23. Nature. 2015 May 14;521(7551):222–226. PubMed PMID: 25754330.
   PubMed Web of Science ®Google Scholar
• Sandborn WJ, Ferrante M, Bhandari BR, et al. Efficacy and safety of anti-interleukin-23 therapy with mirikizumab (LY3074828) in patients with moderate-to-severe ulcerative colitis in a phase 2 study. Gastroenterology. 2018;154(6):S-1360-S-1361.
   Google Scholar
• Liu Z, Yadav PK, Xu X, et al. The increased expression of IL-23 in inflammatory bowel disease promotes intraepithelial and lamina propria lymphocyte inflammatory responses and cytotoxicity. J Leukoc Biol. 2011 Apr;89(4):597–606. PubMed PMID: 21227898.
   PubMed Web of Science ®Google Scholar
• Schmidt C, Giese T, Ludwig B, et al. Expression of interleukin-12-related cytokine transcripts in inflammatory bowel disease: elevated interleukin-23p19 and interleukin-27p28 in Crohn’s disease but not in ulcerative colitis. Inflamm Bowel Dis. 2005 Jan;11(1):16–23. PubMed PMID: 15674109.
   PubMed Web of Science ®Google Scholar
• Schmitt H, Billmeier U, Dieterich W, et al. Expansion of IL-23 receptor bearing TNFR2+ T cells is associated with molecular resistance to anti-TNF therapy in Crohn’s disease. Gut. 2018 May 30 PubMed PMID: 29848778. DOI:10.1136/gutjnl-2017-315671.
   Google Scholar
• Pariente B, Cosnes J, Danese S, et al. Development of the Crohn’s disease digestive damage score, the Lemann score. Inflamm Bowel Dis. 2011 Jun;17(6):1415–1422. PubMed PMID: 21560202; PubMed Central PMCID: PMCPMC3116198.
   PubMed Web of Science ®Google Scholar
• Khanna R, Bressler B, Levesque BG, et al. Early combined immunosuppression for the management of Crohn’s disease (REACT): a cluster randomised controlled trial. Lancet. 2015 Nov 7;386(10006):1825–1834. PubMed PMID: 26342731.
   PubMed Web of Science ®Google Scholar
• Sandborn W, Gasink C, Chan D, et al. PD-012 endoscopic healing in the ustekinumab phase 3 UNITI/IMUNITI Crohn’s disease program and relationship of clinical outcomes to baseline ulceration status. Inflamm Bowel Dis. 2017;23(suppl_1):S9–S9.
   Google Scholar
• Danese S, Feagan B, Sandborn W, et al. OP023 A phase 3b open-label multicentre study (VERSIFY) of the efficacy of vedolizumab on endoscopic healing in moderately to severely active Crohn’s disease (CD). J Crohn’s and Colitis. 2018;12(supplement_1):S016–S017.
   Google Scholar
• Hirten RP, Iacucci M, Shah S, et al. Combining biologics in inflammatory bowel disease and other immune mediated inflammatory disorders. Clin Gastroenterol Hepatol. 2018 Mar 2 PubMed PMID: 29481970. DOI:10.1016/j.cgh.2018.02.024.
   PubMedGoogle Scholar
• Blauvelt A, Papp KA, Griffiths CE, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol. 2017 Mar;76(3):405–417. PubMed PMID: 28057360.
   PubMed Web of Science ®Google Scholar
• Reich K, Armstrong AW, Foley P, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol. 2017 Mar;76(3):418–431. PubMed PMID: 28057361.
   PubMed Web of Science ®Google Scholar
• Reich K, Papp KA, Blauvelt A, et al. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials. Lancet. 2017 Jul 15;390(10091):276–288. PubMed PMID: 28596043.
   PubMed Web of Science ®Google Scholar
• Sandborn WJ, Feagan BG, Wolf DC, et al. Ozanimod induction and maintenance treatment for ulcerative colitis. N Engl J Med. 2016 May 5;374(18):1754–1762. PubMed PMID: 27144850.
   PubMed Web of Science ®Google Scholar
• Panes J, Sandborn WJ, Schreiber S, et al. Tofacitinib for induction and maintenance therapy of Crohn’s disease: results of two phase IIb randomised placebo-controlled trials. Gut. 2017 Jun;66(6):1049–1059. PubMed PMID: 28209624; PubMed Central PMCID: PMCPMC5532457.
   PubMed Web of Science ®Google Scholar
• Vermeire S, Schreiber S, Petryka R, et al. Clinical remission in patients with moderate-to-severe Crohn’s disease treated with filgotinib (the FITZROY study): results from a phase 2, double-blind, randomised, placebo-controlled trial. Lancet. 2017 Jan 21;389(10066):266–275. PubMed PMID: 27988142.
   PubMed Web of Science ®Google Scholar
• Sandborn WJ, Feagan BG, Panes J, et al. Safety and efficacy of ABT-494 (Upadacitinib), an oral jak1 inhibitor, as induction therapy in patients with Crohn’s disease: results from celest. Gastroenterology. 2017;152(5):S1308–S1309.
   Web of Science ®Google Scholar
• Jairath V, Zou G, Parker CE, et al. Systematic review with meta-analysis: placebo rates in induction and maintenance trials of Crohn’s disease. Aliment Pharmacol Ther. 2017 Apr;45(8):1021–1042. PubMed PMID: 28164348.
   PubMed Web of Science ®Google Scholar
• Ma C, Hussein IM, Al-Abbar YJ, et al. Heterogeneity in definitions of efficacy and safety endpoints for clinical trials of Crohn’s disease: a systematic review for development of a core outcome set. Clin Gastroenterol Hepatol. 2018. In press. DOI:10.1016/j.cgh.2018.02.051.
   Web of Science ®Google Scholar
• Hart AL, Lomer M, Verjee A, et al. What are the top 10 research questions in the treatment of inflammatory bowel disease? A priority setting partnership with the James Lind Alliance. J Crohns Colitis. 2017 Feb;11(2):204–211. PubMed PMID: 27506537; PubMed Central PMCID: PMCPMC5266081.
   PubMed Web of Science ®Google Scholar