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Efficacy and Safety of Prostaglandin D2 Receptor 2 Antagonism with Fevipiprant for Patients with Asthma: a Systematic Review and Meta-analysis of Randomized Controlled Trials

  • Asthma (V Ortega, Section Editor)
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Abstract

Purpose of Review

Accumulating evidence has shown that prostaglandin D2 (PGD2)-chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) pathway plays an important role in promoting eosinophilic airway inflammation in asthma. We aimed to assess the efficacy and safety of CRTH2 antagonist fevipiprant in patients with persistent asthma compared with placebo.

Recent Findings

We identified eligible studies by searching PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov. The study was registered as CRD 42020221714 (http://www.crd.york.ac.uk/PROSPERO). Ten randomized controlled trials with 7902 patients met our inclusion criteria. A statistically significant benefit of fevipiprant compared with placebo was shown in improving forced expiratory volume in 1 s (MD 0.05 L, 95% CI: 0.02 to 0.07; p < 0.0001), Asthma Control Questionnaire score (MD -0.10, 95% CI: -0.16 to -0.04; p = 0.001), and Asthma Quality of Life Questionnaire score (MD 0.08, 95% CI: 0.03 to 0.13; p = 0.003). Fevipiprant decreased number of patients with at least one asthma exacerbation requiring administration of systemic corticosteroids for 3 days or more (RR 0.86, 95% CI: 0.77 to 0.97; p = 0.01). Some benefits were a little more pronounced in the high eosinophil population (with an elevated blood eosinophil count or sputum eosinophil percentage) and in the 450 mg dose group. Fevipiprant was well tolerated with no safety issues compared with placebo.

Summary

Fevipiprant could safely improve asthma outcomes compared to placebo. However, most of the differences didn’t reach the minimal clinically important difference (MCID), thus the clinical benefits remained to be confirmed. 

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Abbreviations

ACQ:

Asthma Control Questionnaire

AQLQ:

Asthma Quality of Life Questionnaire

AE:

Adverse events

ASM:

Airway smooth muscle

BAL:

Bronchoalveolar lavage

CENTRAL:

Cochrane Central Register of Controlled Trials

CIs:

Confidence intervals

CRTH2:

Chemoattractant receptor-homologous molecule expressed on type 2 helper T (Th2) cells

DP2 receptor:

PGD2 receptor 2

E.g.:

For example

\({FEV}_{1}\) :

ForcedFEV expiratory volume in 1 s

FeNO:

Fraction exhaled nitric oxide

GINA:

Global Initiative for Asthma

ICS:

Inhaled corticosteroids

IgE:

Immunoglobulin E

IL:

Interleukin

ILC2s:

Type 2 innate lymphoid (cells)

LABA:

Long-acting β agonists

MCID:

Minimal clinically important difference

MD:

Mean difference

\({\mathrm{PGD}}_{2}\) :

Prostaglandin D2

RCTs:

Randomized controlled trials

RR:

Risk ratio

SABA:

Short acting β2-agonist

SAE:

Serious adverse events

SD:

Standard deviation

Th2:

Type 2 helper T (cells)

Tc2:

Type 2 cytotoxic T (cells

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Funding

This study was supported by the National Natural Science Foundation of China (Grant No. 81770035).

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Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, School of Medicine and West China Hospital, Sichuan University, No.37 Guoxue Alley, Chengdu, 610041, West China, China

    Dan Yang, Xinning Guo, Ting Liu, Yina Li, Zhuman Du & Chuntao Liu

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  1. Dan Yang
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Correspondence to Chuntao Liu.

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Yang, D., Guo, X., Liu, T. et al. Efficacy and Safety of Prostaglandin D2 Receptor 2 Antagonism with Fevipiprant for Patients with Asthma: a Systematic Review and Meta-analysis of Randomized Controlled Trials. Curr Allergy Asthma Rep 21, 39 (2021). https://doi.org/10.1007/s11882-021-01017-8

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