Efficacy and Safety of Specific Immunotherapy Combined with Biologics in Allergic Rhinitis and Asthma: A Systematic Review and Network Meta-Analysis

Introduction: Allergic diseases are common clinical diseases. Although allergen-specific immunotherapy (AIT) and biologics have been widely recognized, the clinical efficacy, safety, advantages, and disadvantages of the combined application have not yet been sufficiently recognized. We aimed to investigate the efficacy and safety of AIT combined with biologics in patients with allergic rhinitis and asthma. Methods: PubMed, Embase, the Cochrane Library, and Web of Science were systematically searched to identify studies investigating AIT combined with biologics for treating allergic rhinitis and asthma. The relevant outcome indicators, including incidences of emergency drug use, severe nasal symptoms, severe adverse effects (AEs), local reactions at the site of administration, headache, and general AEs, were collected and extracted. Routine and network meta-analyses were conducted using RevMan-5.4 and STATA-MP-14 to assess efficacy and safety. Results: Eight RCTs and a retrospective study involving 1,494 patients aged 5-65 years with allergic rhinitis and asthma were included in this review. (1) Routine meta-analysis revealed that AIT combined with biologics was significantly better than control treatment (placebo, AIT, or biologics) in terms of the incidence of emergency drug use, severe nasal symptoms, and severe AEs (p = 0.0002; p = 0.01; p = 0.02). However, the differences in the incidence of local reactions at the site of administration, headache, and general AEs were not significant. (2) In the network meta-analysis, compared with AIT or placebo alone, AIT combined with biologics observably reduced the incidence of emergency drug use and severe nasal symptoms (OR = 0.32, 95% CI 0.14-0.73; OR = 0.41, 95% CI: 0.26-0.63). Furthermore, AIT combined with biologics yielded an evidently lower incidence of serious adverse reactions than AIT alone (OR = 0.42, 95% CI: 0.23-0.74). Conclusion: The combined application of AIT and biologics has promising prospects in the clinical treatment of allergic rhinitis and asthma due to the improvement of both clinical efficacy and safety (trial registration: Systemic Review Registration; PROSPERO #CRD42024496277).