Comparison of adverse events between cluster and conventional immunotherapy for allergic rhinitis patients with or without asthma: A systematic review and meta-analysis

Background: Cluster schedule of allergen-specific immunotherapy (AIT) is a cost-effective choice for allergic rhinitis (AR) patients, but its safety has been questioned due to the greater dosages required at each treatment compared with conventional immunotherapy. It remains a question that whether cluster schedule leads to a higher risk of side effects. Objective: This study was designed to update the evidence and investigate whether cluster schedule leads to a higher risk of local adverse reactions (LARs) and systemic adverse reactions (SARs) than cluster schedule does. Methods: We searched the Cochrane Central Register of Controlled Trials, EMBASE and Medline thoroughly and included studies comparing cluster and conventional schedules. A meta-analysis of 5 outcomes related to adverse events was performed after bias and heterogeneity assessments. And as a result of language limitations, we considered only articles in Chinese and English. Results: 5 observational studies and 6 interventional studies were included in the meta-analysis. There were no differences between cluster and conventional schedules when analyzing SARs by the number of patients, delayed SARs, grade 2 SARs and LARs. Analyses of SARs by injection, grade 1 SARs and LARs by injection in observational studies showed that cluster schedule had a lower risk of adverse events than did conventional schedule. Conclusion: Our data suggest that cluster schedule is as safe as or even safer than conventional schedule for AR patients with or without asthma (AS).