Role of Roflumilast in Ulcerative Colitis

Summary

This study aims to investigate possible efficacy and safety of Roflumilast in adult patients with ulcerative colitis disease .

Timeline

Start

2023-02-01

Primary completion

2024-04-15

Completion

2024-09-15

Publications

• Background Feuerstein JD, Cheifetz AS. Ulcerative colitis: epidemiology, diagnosis, and management. Mayo Clin Proc. 2014 Nov;89(11):1553-63. doi: 10.1016/j.mayocp.2014.07.002. Epub 2014 Sep 8.
• Background Thrash B, Patel M, Shah KR, Boland CR, Menter A. Cutaneous manifestations of gastrointestinal disease: part II. J Am Acad Dermatol. 2013 Feb;68(2):211.e1-33; quiz 244-6. doi: 10.1016/j.jaad.2012.10.036.
• Background Neurath MF. Targeting immune cell circuits and trafficking in inflammatory bowel disease. Nat Immunol. 2019 Aug;20(8):970-979. doi: 10.1038/s41590-019-0415-0. Epub 2019 Jun 24.
• Background de Souza HSP, Fiocchi C, Iliopoulos D. The IBD interactome: an integrated view of aetiology, pathogenesis and therapy. Nat Rev Gastroenterol Hepatol. 2017 Dec;14(12):739-749. doi: 10.1038/nrgastro.2017.110. Epub 2017 Aug 23.
• Background Elbadry M, Nour MO, Hussien M, Ghoneem EA, Medhat MA, Shehab H, Galal S, Eltabbakh M, El-Raey F, Negm M, Afify S, Abdelhamed W, Sherief A, Abdelaziz A, Abo Elkasem M, Mahrous A, Kamal G, Maher M, Abdel-Hameed O, Elbasuny A, El-Zayyadi I, Bassiony A, Moussa A, Bedewy E, Elfert A, El Kassas M. Clinico-Epidemiological Characteristics of Patients With Inflammatory Bowel Disease in Egypt: A Nationwide Multicenter Study. Front Med (Lausanne). 2022 Apr 19;9:867293. doi: 10.3389/fmed.2022.867293. eCollection 2022.
• Background Fujita Y, Khateb A, Li Y, Tinoco R, Zhang T, Bar-Yoseph H, Tam MA, Chowers Y, Sabo E, Gerassy-Vainberg S, Starosvetsky E, James B, Brown K, Shen-Orr SS, Bradley LM, Tessier PA, Ronai ZA. Regulation of S100A8 Stability by RNF5 in Intestinal Epithelial Cells Determines Intestinal Inflammation and Severity of Colitis. Cell Rep. 2018 Sep 18;24(12):3296-3311.e6. doi: 10.1016/j.celrep.2018.08.057.
• Background Zundler S, Becker E, Schulze LL, Neurath MF. Immune cell trafficking and retention in inflammatory bowel disease: mechanistic insights and therapeutic advances. Gut. 2019 Sep;68(9):1688-1700. doi: 10.1136/gutjnl-2018-317977. Epub 2019 May 24.
• Background Trivedi PJ, Adams DH. Chemokines and Chemokine Receptors as Therapeutic Targets in Inflammatory Bowel Disease; Pitfalls and Promise. J Crohns Colitis. 2018 Nov 28;12(12):1508. doi: 10.1093/ecco-jcc/jjy130. No abstract available.
• Background Zhang X, Dong G, Li H, Chen W, Li J, Feng C, Gu Z, Zhu F, Zhang R, Li M, Tang W, Liu H, Xu Y. Structure-Aided Identification and Optimization of Tetrahydro-isoquinolines as Novel PDE4 Inhibitors Leading to Discovery of an Effective Antipsoriasis Agent. J Med Chem. 2019 Jun 13;62(11):5579-5593. doi: 10.1021/acs.jmedchem.9b00518. Epub 2019 May 31.
• Background Raker VK, Becker C, Steinbrink K. The cAMP Pathway as Therapeutic Target in Autoimmune and Inflammatory Diseases. Front Immunol. 2016 Mar 31;7:123. doi: 10.3389/fimmu.2016.00123. eCollection 2016.
• Background Li H, Li J, Zhang X, Feng C, Fan C, Yang X, Zhang R, Zhu F, Zhou Y, Xu Y, Liu H, Tang W. DC591017, a phosphodiesterase-4 (PDE4) inhibitor with robust anti-inflammation through regulating PKA-CREB signaling. Biochem Pharmacol. 2020 Jul;177:113958. doi: 10.1016/j.bcp.2020.113958. Epub 2020 Apr 3.
• Background Li H, Fan C, Feng C, Wu Y, Lu H, He P, Yang X, Zhu F, Qi Q, Gao Y, Zuo J, Tang W. Inhibition of phosphodiesterase-4 attenuates murine ulcerative colitis through interference with mucosal immunity. Br J Pharmacol. 2019 Jul;176(13):2209-2226. doi: 10.1111/bph.14667. Epub 2019 May 17.
• Background Zebda R, Paller AS. Phosphodiesterase 4 inhibitors. J Am Acad Dermatol. 2018 Mar;78(3 Suppl 1):S43-S52. doi: 10.1016/j.jaad.2017.11.056. Epub 2017 Dec 15.
• Background Kokkonen K, Kass DA. Nanodomain Regulation of Cardiac Cyclic Nucleotide Signaling by Phosphodiesterases. Annu Rev Pharmacol Toxicol. 2017 Jan 6;57:455-479. doi: 10.1146/annurev-pharmtox-010716-104756. Epub 2016 Oct 12.
• Background Faleiro L, Kobayashi R, Fearnhead H, Lazebnik Y. Multiple species of CPP32 and Mch2 are the major active caspases present in apoptotic cells. EMBO J. 1997 May 1;16(9):2271-81. doi: 10.1093/emboj/16.9.2271.
• Background Kosutova P, Mikolka P, Kolomaznik M, Balentova S, Adamkov M, Calkovska A, Mokra D. Reduction of lung inflammation, oxidative stress and apoptosis by the PDE4 inhibitor roflumilast in experimental model of acute lung injury. Physiol Res. 2018 Dec 31;67(Suppl 4):S645-S654. doi: 10.33549/physiolres.934047.

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