Application of Omalizumab combined with allergen immunotherapy in the treatment of allergic asthma in children / 中华实用儿科临床杂志

ABSTRACT

Objective:To analyze the efficacy and safety of Omalizumab (OMA) combined with allergen immunotherapy (AIT) on children with allergic asthma.Methods:Clinical data of 43 children with allergic asthma from the Second Hospital of Tianjin Medical University between August 2018 and October 2022, who were managed by OMA combined with double mite subcutaneous immunotherapy (SCIT) were retrospectively analyzed, including 30 males and 13 females with the age of 5-15 years.Twenty children with allergic asthma who were managed by the monotherapy for SCIT during the same period, including 16 males and 4 females with the age of 4-13 years were included in the control group(group1: conventional immunotherapy; group2: cluster immunotherapy). Among the 43 cases managed by OMA combined with SCIT, 20 were treated with OMA, followed by AIT (OMA-AIT group), and 23 were treated with AIT, followed by OMA (AIT-OMA group). Notably, 6 cases in AIT-OMA group who were additionally given OMA due to the difficulty in increasing doses were subgrouped in AO1 group, and 17 who were additionally given OMA due to poor control of asthma or comorbidities during the course of AIT and frequent adverse events were subgrouped in AO2 group.The number of asthma exacerbations within 1 year and during the combination therapy, the Childhood Asthma Control Test/Asthma Control Test (C-ACT/ACT) findings, the Visual Analogue Scale (VAS) for grading rhinitis, inhaled corticosteroid (ICS) dosage converted to budesonide equivalent, the Total Medication Score (TMS), comorbidities, lung function [percent-predicted forced expiratory volume in 1 second(FEV 1% pred), percent-predicted peak expiratory flow(PEF%pred), percent-predicted maximal mild-expiratory flow(MMEF%pred)], exhaled nitric oxide (FeNO), completion of the initial SCIT and adverse effects [local adverse reactions (LRs) and systemic adverse reactions (SRs)] were analyzed for assessing the efficacy and safety of OMA combined with AIT on children with allergic asthma.The t-test of two independent samples was used for comparison of measurement data that followed normal distribution.Wilcoxon′s test was used for non-normally distributed between-group comparisons.The χ2 test was used for the between-group comparison of counting data. Results:(1)Baseline comparison showed that the male ratio (17/20 cases vs.13/23 cases) and the proportion of moderate-to-severe persistent asthma (18/20 cases vs.18/23 cases) in the OMA-AIT group were significantly higher than those of the AIT-OMA group (all P<0.05). (2)Efficacy: ①In OMA-AIT group, all children reached the AIT maintenance treatment stage successfully after combination therapy.At the maintenance treatment stage, the C-ACT/ACT, VAS and TMS scores(26.0±1.25 vs.24.55±2.28, 1.50±1.24 vs.2.55±1.70, 3.60±1.47 vs.5.45±1.19)were significantly improved from baseline(all P<0.05). There were no significant differences in lung function indexes FEV 1%pred, PEF%pred, and MMEF%pred ( P>0.05), and FeNO level did not change significantly than baseline.After the combination treatment, ICS dosage significantly decreased from 240.00 (160.00, 380.00) μg/d at baseline to 140.00 (80.00, 300.00) μg/d ( P<0.05). Comorbidities, including allergic rhinitis, food allergy, atopic dermatitis and angioedema were improved.Five cases (25.00%) had once asthma exacerbation during the treatment.The duration of maintenance dose of conventional (22.70±7.10 vs.15.20±1.32) and cluster immunotherapy (13.00±4.97 vs.7.30±1.06) were longer than those of the corresponding control group(all P<0.05). ②AIT-OMA group: In AO1 group, the C-ACT/ACT score were improved from baseline( P<0.05), and VAS score, TMS score decreased from 3.00(1.75, 3.00), (4.67±1.97) points at baseline to 1.00(0, 1.00), (2.83±1.60) points by the maintenance dose in AO1 group (all P<0.05). There were no significant differences in the FEV 1%pred, PEF%pred, MMEF%pred and FeNO compared with baseline in AO1 group.ICS dosage in AO1 group significantly decreased from (180.00±78.99) μg/d at baseline to (88.88±26.23) μg/d ( P<0.05). In AO2 group, the C-ACT/ACT, VAS and TMS scores at the completion of OMA treatment[26.53±0.94 vs.25.06±2.05, 1.00 (0, 2.00) vs.2.00(2.00, 3.50), 3.41±0.94 vs.5.53±1.23]were significantly improved from baseline (all P<0.05). PEF%pred[(106.47±22.37)% vs.(94.47±26.39)%] significantly increased than baseline ( P<0.05), and the remaining lung function indexes and FeNO were not significantly improved.ICS dosage significantly decreased from 240.00(160.00, 400.00) μg/d at baseline to 80.00 (20.00, 160.00) μg/d ( P<0.05). During the combination treatment, 1 case (5.88%) had once asthma exacerbation, and all 8 cases with food allergy or atopic dermatitis or conjunctivitis had improved comorbidities.(3)Safety: adverse events during OMA injection were not reported.①In OMA-AIT group, a total of 165 OMA injections were performed in the initial treatment stage of the conventional immunotherapy group, with 13 (7.88%) reported LRs and 2 (1.21%) grade-1 SRs.A total of 143 OMA injections were performed in the initial treatment stage of the cluster immunotherapy group, with 19(13.29%) reported LRs and none of SRs.②In AIT-OMA group, there were 6 cases of adverse events in the initial treatment stage of AIT who were successfully reached the maintenance treatment stage after the addition of OMA in AO1 group.In AO2 group, children who were additionally given OMA due to adverse events in the maintenance treatment phase did not report adverse events during the combination therapy. Conclusions:OMA combined with AIT not only expands the scope of AIT, improves allergic and asthma symptoms in children, reduces the use of drugs, but also enhance the safety of AIT and compliance, reduces adverse events during AIT treatment, and even shortens the time of initial treatment.