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28.12.2023 | Original Research Paper

Sphingosine 1-phosphate (S1P) receptor modulators as an induction and maintenance therapy for ulcerative colitis: a systematic review and meta-analysis of randomized controlled trials

verfasst von: Husam Abu Suilik, Fouad Jaber, Mohamed Abuelazm, Alaa Ramadan, Mohamed A. Elzeftawy, Amr Elrosasy, Rana Ahmed Youssef, Basel Abdelazeem, Jana G. Hashash, Francis A. Farraye, Hassan Ghoz

Erschienen in: Inflammation Research | Ausgabe 2/2024

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Abstract

Background and objective

One sphingosine-1-phosphate (S1P) receptor modulator is approved (ozanimod) and another (etrasimod) is under investigation for the induction and maintenance of remission of ulcerative colitis (UC). We aim to evaluate the efficacy and safety of S1P modulators in patients with active UC.

Methods

We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching: PubMed, Web of Science, SCOPUS, and Cochrane through May 13th, 2023. We used the fixed-effect model to pool dichotomous data using risk ratio (RR) with a 95% confidence interval (CI).

Results

Five RCTs with a total of 1990 patients were included. S1P receptor modulators were significantly associated with increased clinical response during both the induction (RR 1.71 with 95% CI [1.50, 1.94], P = 0.00001) and maintenance phases (RR 1.89 with 95% CI [1.33, 2.69], P = 0.0004); clinical remission rates during both induction (RR 2.76 with 95% CI [1.88, 4.05], P = 0.00001) and maintenance phases (RR 3.34 with 95% CI [1.41, 7.94], P = 0.006); endoscopic improvement during both induction (RR 2.15 with 95% CI [1.71, 2.70], P = 0.00001) and maintenance phases (RR 2.41 with 95% CI [1.15, 5.05], P = 0.02); and histologic remission during both induction (RR 2.60 with 95% CI [1.89, 3.57] [1.17, 2.10], P = 0.00001) and maintenance phases (RR 2.52 with 95% CI [1.89, 3.37], P = 0.00001). Finally, there was no difference regarding safety outcomes as compared to placebo in both the induction and maintenance phases.

Conclusion

S1P receptor modulators are effective in inducing and maintaining remission in patients with moderate to severe UC.

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Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults: American college of gastroenterology, practice parameters committee. Am J Gastroenterol. 2010;105:501–23.CrossRefPubMed

Ungaro R, Mehandru S, Allen PB, et al. Ulcerative colitis. Lancet. 2017;389:1756–1770. https://pubmed.ncbi.nlm.nih.gov/27914657/.

Olivera P, Danese S, Peyrin-Biroulet L. Next generation of small molecules in inflammatory bowel disease. Gut. 2017;66:199–209. https://pubmed.ncbi.nlm.nih.gov/27856614/.

Sandborn WJ, Feagan BG, Wolf DC, et al. Ozanimod induction and maintenance treatment for ulcerative colitis. N Engl J Med. 2016;374:1754–62. https://doi.org/10.1056/NEJMoa1513248.CrossRefPubMed

Sandborn WJ, Vermeire S, Peyrin-Biroulet L, et al. Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies. Lancet. 2023;401:1159–71. https://doi.org/10.1016/S0140-6736(23)00061-2.CrossRefPubMed

Kihara Y, Maceyka M, Spiegel S, et al. Lysophospholipid receptor nomenclature review: IUPHAR Review 8. Br J Pharmacol. 2014;171:3575–94.CrossRefPubMedPubMedCentral

Pérez-Jeldres T, Tyler CJ, Boyer JD, et al. Cell trafficking interference in inflammatory bowel disease: therapeutic interventions based on basic pathogenesis concepts. Inflamm Bowel Dis. 2019;25:270–82.CrossRefPubMed

Sandborn WJ, Peyrin-Biroulet L, Zhang J, et al. Efficacy and safety of etrasimod in a phase 2 randomized trial of patients with ulcerative colitis. Gastroenterology. 2020;158:550–61.CrossRefPubMed

Blaho VA, Hla T. Thematic review series: Lysophospholipids and their receptors: an update on the biology of sphingosine 1-phosphate receptors. J Lipid Res. 2014;55:1596–608.CrossRefPubMedPubMedCentral

10.

Camm J, Hla T, Bakshi R, et al. Cardiac and vascular effects of fingolimod: Mechanistic basis and clinical implications. Am Heart J. 2014;168:632–44.CrossRefPubMed

11.

Marsolais D, Rosen H. Chemical modulators of sphingosine-1-phosphate receptors as barrier-oriented therapeutic molecules. Nat. Rev. Drug Discov. 2009;8:297–307. https://pubmed.ncbi.nlm.nih.gov/19300460/.

12.

Mandala S, Hajdu R, Bergstrom J, et al. Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science (-80). 2002;296:346–9.CrossRef

13.

Gräler MH, Goetzl EJ. The immunosuppressant FTY720 down-regulates sphingosine 1-phosphate G-protein-coupled receptors. FASEB J. 2004;18:551–3.CrossRefPubMed

14.

Brinkmann V, Billich A, Baumruker T, et al. Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov. 2010;9:883–97.CrossRefPubMed

15.

Garris CS, Blaho VA, Hla T, et al. Sphingosine-1-phosphate receptor 1 signalling in T cells: trafficking and beyond. Immunology. 2014;142:347–53.CrossRefPubMedPubMedCentral

16.

Arlt O, Schwiebs A, Japtok L, et al. Sphingosine-1-phosphate modulates dendritic cell function: Focus on non-migratory effects in vitro and in vivo. Cell Physiol Biochem. 2014;34:27–44.CrossRefPubMed

17.

Walzer T, Chiossone L, Chaix J, et al. Natural killer cell trafficking in vivo requires a dedicated sphingosine 1-phosphate receptor. Nat Immunol. 2007;8:1337–44.CrossRefPubMed

18.

Xiong Y, Hla T. S1P control of endothelial integrity. Curr. Top. Microbiol. Immunol. 2014;378:85–105. https://pubmed.ncbi.nlm.nih.gov/24728594/.

19.

Brinkmann V, Baumruker T. Pulmonary and vascular pharmacology of sphingosine 1-phosphate. Curr Opin Pharmacol. 2006;6:244–50.CrossRefPubMed

20.

Jain N, Bhatti MT. Fingolimod-associated macular edema: Incidence, detection, and management. Neurology. 2012;78:672–680. https://pubmed.ncbi.nlm.nih.gov/22371414/.

21.

Anon. Gilenya [package insert], E.H., NJ: Novartis; Pharmaceuticals Corp. 2016.

22.

Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362:402–15.CrossRefPubMed

23.

Calabresi PA, Radue EW, Goodin D, et al. Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2014;13:545–56.CrossRefPubMed

24.

Peyrin-Biroulet L, Christopher R, Behan D, et al. Modulation of sphingosine-1-phosphate in inflammatory bowel disease. Autoimmun Rev. 2017;16:495–503.CrossRefPubMed

25.

Al-Shamma H, Lehmann-Bruinsma K, Carroll C, et al. The selective sphingosine 1-phosphate receptor modulator etrasimod regulates lymphocyte trafficking and alleviates experimental colitis. J Pharmacol Exp Ther. 2019;369:311–7.CrossRefPubMed

26.

Cohen JA, Arnold DL, Comi G, et al. Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016;15:373–81.CrossRefPubMed

27.

Scott FL, Clemons B, Brooks J, et al. Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1) and receptor-5 (S1P5) agonist with autoimmune disease-modifying activity. Br J Pharmacol. 2016;173:1778–92.CrossRefPubMedPubMedCentral

28.

Sandborn WJ, Feagan BG, D’Haens G, et al. Ozanimod as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2021;385:1280–91.CrossRefPubMed

29.

Anon. Highlights of prescribing information. Zeposia (ozanimod) capsules. 2020. Jan 9, 2023]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209899s000lbl.pdf.

30.

Buzard DJ, Kim SH, Lopez L, et al. Discovery of APD334: design of a clinical stage functional antagonist of the sphingosine-1-phosphate-1 receptor. ACS Med Chem Lett. 2014;5:1313–7.CrossRefPubMedPubMedCentral

31.

Lee C, Taylor C, Tang Y, et al. P207 Effects of fluconazole, gemfibrozil, and rifampin on the pharmacokinetics, safety, and tolerability of etrasimod. In: 2022:A142.1-A142

32.

Vermeire S, Chiorean M, Panés J, et al. Long-term safety and efficacy of etrasimod for ulcerative colitis: results from the open-label extension of the OASIS study. J Crohn’s Colitis. 2021;15:950–9.CrossRef

33.

Higgins JPT, Thomas J, Chandler J, et al. Cochrane handbook for systematic reviews of interventions. Cochrane Handb Syst Rev Interv. 2019. https://doi.org/10.1002/9781119536604.CrossRef

34.

Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. PLoS Med. 2021;18:e1003583. https://doi.org/10.1371/journal.pmed.1003583.CrossRefPubMedPubMedCentral

35.

Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366. https://www.bmj.com/content/366/bmj.l4898 [Accessed July 16, 2022].

36.

Guyatt GH, Oxman AD, Vist GE, et al. GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336:924–6.CrossRefPubMedPubMedCentral

37.

Guyatt GH, Oxman AD, Kunz R, et al. GRADE: what is “quality of evidence” and why is it important to clinicians? Chinese J. Evidence-Based Med. 2009;9:133–137. https://www.bmj.com/content/336/7651/995.

38.

Anon. Review Manager (RevMan). Version 5.4, The Cochrane Collaboration. 2020.

39.

Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–76.CrossRefPubMed

40.

Sandborn WJ, Van AG, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012;142:253–7.CrossRef

41.

Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369:699–710.CrossRefPubMed

42.

Sands BE, Sandborn WJ, Panaccione R, et al. Ustekinumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2019;381:1201–14.CrossRefPubMed

43.

Feagan BG, Danese S, Loftus EV, et al. Filgotinib as induction and maintenance therapy for ulcerative colitis (SELECTION): a phase 2b/3 double-blind, randomised, placebo-controlled trial. Lancet. 2021;397:2372–84. https://doi.org/10.1016/S0140-6736(21)00666-8.CrossRefPubMed

44.

Danese S, Vermeire S, Zhou W, et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. Lancet. 2022;399:2113–28.CrossRefPubMed

45.

Juif PE, Kraehenbuehl S, Dingemanse J. Clinical pharmacology, efficacy, and safety aspects of sphingosine-1-phosphate receptor modulators. Expert Opin Drug Metab Toxicol. 2016;12:879–95.CrossRefPubMed

46.

Kiyomi K, Caroline L, Lisette A, et al. P045 effect of etrasimod on circulating lymphocyte subsets: data from a randomized phase 1 study in healthy japanese and caucasian men. Am J Gastroenterol. 2020;115:S12.CrossRefPubMed

47.

Siegmund B, Melmed GY, Irving PM, et al. P402 Incidence and outcomes of herpes zoster in the ozanimod phase, 3 ulcerative colitis and relapsing multiple sclerosis clinical program. J Crohn’s Colitis. 2022;16:i395–6.CrossRef

48.

Singh S, Allegretti JR, Siddique SM, et al. AGA technical review on the management of moderate to severe ulcerative colitis. Gastroenterology. 2020;158:1465-1496.e17.CrossRefPubMed

49.

Agrawal M, Kim ES, Colombel JF. Jak inhibitors safety in ulcerative colitis: Practical implications. J Crohn’s Colitis. 2020;14:S755–60.CrossRef

50.

Kappos L, Radue E-W, O’Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010;362:387–401.CrossRefPubMed

51.

Tran JQ, Hartung JP, Peach RJ, et al. Results from the first-in-human study with ozanimod, a novel, selective sphingosine-1-phosphate receptor modulator. J Clin Pharmacol. 2017;57:988–96.CrossRefPubMedPubMedCentral

52.

Vaclavkova A, Chimenti S, Arenberger P, et al. Oral ponesimod in patients with chronic plaque psoriasis: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet. 2014;384:2036–45.CrossRefPubMed

53.

Cannavo A, Liccardo D, Komici K, et al. Sphingosine kinases and sphingosine 1-phosphate receptors: Signaling and actions in the cardiovascular system. Front Pharmacol. 2017. https://doi.org/10.3389/fphar.2017.00556.CrossRefPubMedPubMedCentral

54.

Gergely P, Nuesslein-Hildesheim B, Guerini D, et al. The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate. Br J Pharmacol. 2012;167:1035–47.CrossRefPubMedPubMedCentral

Titel: Sphingosine 1-phosphate (S1P) receptor modulators as an induction and maintenance therapy for ulcerative colitis: a systematic review and meta-analysis of randomized controlled trials
verfasst von: Husam Abu Suilik
Fouad Jaber
Mohamed Abuelazm
Alaa Ramadan
Mohamed A. Elzeftawy
Amr Elrosasy
Rana Ahmed Youssef
Basel Abdelazeem
Jana G. Hashash
Francis A. Farraye
Hassan Ghoz
Publikationsdatum: 28.12.2023
Verlag: Springer International Publishing
Erschienen in: Inflammation Research / Ausgabe 2/2024
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-023-01829-6

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Background and objective

Methods

Results

Conclusion

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