Date Published: January 31, 2019
Publisher: Public Library of Science
Author(s): Hang Li, Kai Wang, Huiting Huang, Wenbin Cheng, Xiaohong Liu, Lise Lotte Gluud.
More and more clinical trials have tried to assess the clinical benefit of anti-interleukin (IL)-13 monoclonal antibodies for uncontrolled asthma. The aim of this study is to evaluate the efficacy and safety of anti-IL-13 monoclonal antibodies for uncontrolled asthma. Major databases were searched for randomized controlled trials comparing the anti-IL-13 treatment and a placebo in uncontrolled asthma. Outcomes, including asthma exacerbation rate, forced expiratory volume in 1 second (FEV1), Asthma Quality of Life Questionnaire (AQLQ) scores, rescue medication use, and adverse events were extracted from included studies for systematic review and meta-analysis. Five studies involving 3476 patients and two anti-IL-13 antibodies (lebrikizumab and tralokinumab) were included in this meta-analysis. Compared to the placebo, anti-IL-13 treatments were associated with significant improvement in asthma exacerbation, FEV1 and AQLQ scores, and reduction in rescue medication use. Adverse events and serious adverse events were similar between two groups. Subgroup analysis showed patients with high periostin level had a lower risk of asthma exacerbation after receiving anti-IL-13 treatment. Our study suggests that anti-IL-13 monoclonal antibodies could improve the management of uncontrolled asthma. Periostin may be a good biomarker to detect the specific subgroup who could get better response to anti-IL-13 treatments. In view of blocking IL-13 alone is possibly not enough to achieve asthma control because of the overlapping pathophysiological roles of IL-13/IL-4 in inflammatory pathways, combined blocking of IL-13 and IL-4 with monoclonal antibodies may be more encouraging.
With the clinical use of inhaled corticosteroid (ICS) and long-acting inhaled bronchodilators, the symptoms of most of asthma patients can be well controlled. However, despite regular treatment in current guidelines, there are still about 40% of asthma patients still have trouble controlling their symptoms[1, 2]. Unsatisfactory control of symptom is closely related to an increased risk of asthma exacerbation and mortality—impairing patients’ life quality and accounting for a high financial burden[3, 4]. Thus, it is quite necessary to improve management and control of asthma. Some novel therapeutic options for uncontrolled asthma have been used in clinic or undergoing clinical trials. Some monoclonal antibodies, such as anti-Interleukin (IL)-5 (benralizumab and mepolizumab) and anti-IgE (omalizumab), have showed clinical efficacy in treating severe refractory asthma by inhibiting T helper 2 (Th2) cytokine-mediated inflammation response[5, 6]. They have been recommended to be add-on treatments for asthma in Global Initiative for Asthma (GINA) guideline.
Asthma is a heterogeneous disease with different phenotypes, clinical features, and responses to treatments [22, 23]. Specific molecular patterns in different phenotypes of asthma could be possible target of treatment. Some patients with uncontrolled asthma still have a high level of IL-13 even when treated by inhaled or systemic glucocorticoid, which is consistent with the hypothesis that IL-13 can contribute to steroid resistance[25, 26]. A systematic review published in 2016 assessed the efficacy of anti-IL-13 antibodies in patients with mild to severe asthma. It showed anti-IL-13 antibodies could improve peak expiratory flow, decrease FeNO and asthma exacerbation. However, that systematic review included asthma patients in different severity from mild to severe, and it didn’t assess the possibility of periostin level as biomarker for anti-IL-13 treatments. Our meta-analysis focused on studying patients with uncontrolled asthma, because mild asthma could be comparatively easier to be controlled by common therapies. In the 2017 GINA guideline, anti-IL-13 therapies haven’t been recommended to be add-on treatments for asthma. Our meta-analysis investigated the potential of anti-IL-13 to be an addition on current asthma controller therapies in patients with uncontrolled asthma.