Spotlight on Fevipiprant and Its Potential in the Treatment of Asthma: Evidence to Date

Overview

Journal J Asthma Allergy

Publisher Dove Medical Press

Date 2019 Jan 22

PMID 30662272

Citations 6

Authors

Christina C Kao

Amit D Parulekar

Affiliations

Soon will be listed here.

Abstract

Asthma is a heterogeneous disease, which may be classified into phenotypes and endotypes based on clinical characteristics and molecular mechanisms. The best described endotype of severe asthma is type 2 (T2)-high asthma, characterized by release of inflammatory cytokines by T helper 2 (T2) cells and type 2 innate lymphoid cells cells. Prostaglandin D2 contributes to T2 inflammation through binding of the G-protein-coupled receptor chemoattractant receptor-homologous molecule expressed on T2 cells (CRTH2). Fevipiprant is an oral competitive antagonist of CRTH2. Early-phase trials have demonstrated safety and potential efficacy in patients with asthma, specifically, improvement in FEV and eosinophilic airway inflammation. However, no clear biomarker identified patients who responded favorably to fevipiprant, although patients with moderate-to-severe asthma and evidence of T2 inflammation may be more likely to respond to treatment. Additional studies are needed to determine the efficacy and target population for use of this drug in patients with asthma.

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References

Nagata K, Hirai H, Tanaka K, Ogawa K, Aso T, Sugamura K . CRTH2, an orphan receptor of T-helper-2-cells, is expressed on basophils and eosinophils and responds to mast cell-derived factor(s). FEBS Lett. 1999; 459(2):195-9. DOI: 10.1016/s0014-5793(99)01251-x. View

Hirai H, Tanaka K, Yoshie O, Ogawa K, Kenmotsu K, Takamori Y . Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. J Exp Med. 2001; 193(2):255-61. PMC: 2193345. DOI: 10.1084/jem.193.2.255. View

Gervais F, Cruz R, Chateauneuf A, Gale S, Sawyer N, Nantel F . Selective modulation of chemokinesis, degranulation, and apoptosis in eosinophils through the PGD2 receptors CRTH2 and DP. J Allergy Clin Immunol. 2001; 108(6):982-8. DOI: 10.1067/mai.2001.119919. View

Kabashima K, Narumiya S . The DP receptor, allergic inflammation and asthma. Prostaglandins Leukot Essent Fatty Acids. 2003; 69(2-3):187-94. DOI: 10.1016/s0952-3278(03)00080-2. View

Crea A, Nakhosteen J, Lee T . Mediator concentrations in bronchoalveolar lavage fluid of patients with mild asymptomatic bronchial asthma. Eur Respir J. 1992; 5(2):190-5. View

Johnston S, Bardin P, Harrison J, Ritter W, Joubert J, Holgate S . The effects of an oral thromboxane TP receptor antagonist BAY u 3405, on prostaglandin D2- and histamine-induced bronchoconstriction in asthma, and relationship to plasma drug concentrations. Br J Clin Pharmacol. 1992; 34(5):402-8. PMC: 1381468. DOI: 10.1111/j.1365-2125.1992.tb05649.x. View

Hata A, Breyer R . Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation. Pharmacol Ther. 2004; 103(2):147-66. DOI: 10.1016/j.pharmthera.2004.06.003. View

Kostenis E, Ulven T . Emerging roles of DP and CRTH2 in allergic inflammation. Trends Mol Med. 2006; 12(4):148-58. DOI: 10.1016/j.molmed.2006.02.005. View

Takatsu K, Nakajima H . IL-5 and eosinophilia. Curr Opin Immunol. 2008; 20(3):288-94. DOI: 10.1016/j.coi.2008.04.001. View

10.

Moore W, Meyers D, Wenzel S, Teague W, Li H, Li X . Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med. 2009; 181(4):315-23. PMC: 2822971. DOI: 10.1164/rccm.200906-0896OC. View

11.

Levine S, Wenzel S . Narrative review: the role of Th2 immune pathway modulation in the treatment of severe asthma and its phenotypes. Ann Intern Med. 2010; 152(4):232-7. PMC: 2846792. DOI: 10.7326/0003-4819-152-4-201002160-00008. View

12.

Mutalithas K, Guillen C, Day C, Brightling C, Pavord I, Wardlaw A . CRTH2 expression on T cells in asthma. Clin Exp Immunol. 2010; 161(1):34-40. PMC: 2901512. DOI: 10.1111/j.1365-2249.2010.04161.x. View

13.

Balzar S, Fajt M, Comhair S, Erzurum S, Bleecker E, Busse W . Mast cell phenotype, location, and activation in severe asthma. Data from the Severe Asthma Research Program. Am J Respir Crit Care Med. 2010; 183(3):299-309. PMC: 3056228. DOI: 10.1164/rccm.201002-0295OC. View

14.

Siroux V, Basagana X, Boudier A, Pin I, Garcia-Aymerich J, Vesin A . Identifying adult asthma phenotypes using a clustering approach. Eur Respir J. 2011; 38(2):310-7. DOI: 10.1183/09031936.00120810. View

15.

Barnes N, Pavord I, Chuchalin A, Bell J, Hunter M, Lewis T . A randomized, double-blind, placebo-controlled study of the CRTH2 antagonist OC000459 in moderate persistent asthma. Clin Exp Allergy. 2011; 42(1):38-48. DOI: 10.1111/j.1365-2222.2011.03813.x. View

16.

Busse W, Wenzel S, Meltzer E, Kerwin E, Liu M, Zhang N . Safety and efficacy of the prostaglandin D2 receptor antagonist AMG 853 in asthmatic patients. J Allergy Clin Immunol. 2012; 131(2):339-45. DOI: 10.1016/j.jaci.2012.10.013. View

17.

Fajt M, Gelhaus S, Freeman B, Uvalle C, Trudeau J, Holguin F . Prostaglandin D₂ pathway upregulation: relation to asthma severity, control, and TH2 inflammation. J Allergy Clin Immunol. 2013; 131(6):1504-12. PMC: 3889167. DOI: 10.1016/j.jaci.2013.01.035. View

18.

Liu M, Bleecker E, Lichtenstein L, Niv Y, McLemore T, PERMUTT S . Evidence for elevated levels of histamine, prostaglandin D2, and other bronchoconstricting prostaglandins in the airways of subjects with mild asthma. Am Rev Respir Dis. 1990; 142(1):126-32. DOI: 10.1164/ajrccm/142.1.126. View

19.

Xue L, Salimi M, Panse I, Mjosberg J, McKenzie A, Spits H . Prostaglandin D2 activates group 2 innate lymphoid cells through chemoattractant receptor-homologous molecule expressed on TH2 cells. J Allergy Clin Immunol. 2014; 133(4):1184-94. PMC: 3979107. DOI: 10.1016/j.jaci.2013.10.056. View

20.

Pettipher R, Hunter M, Perkins C, Collins L, Lewis T, Baillet M . Heightened response of eosinophilic asthmatic patients to the CRTH2 antagonist OC000459. Allergy. 2014; 69(9):1223-32. DOI: 10.1111/all.12451. View