Efficacy and Safety of Sublingual versus Subcutaneous Immunotherapy for Patients with Allergic Rhinitis with Asthma: A Systematic Review and Meta-analysis.

Abstract

Introduction: Allergic rhinitis (AR) and asthma are common chronic respiratory disorders that frequently coexist. Allergen immunotherapy (AIT) is a disease-modifying treatment; however, the comparative efficacy and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) remain uncertain in patients with concomitant AR and asthma.

Methods: PubMed/MEDLINE, Scopus, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception to March 2026. Studies directly comparing SCIT and SLIT in patients with AR and concomitant asthma were eligible. Outcomes included symptom scores, medication use, reported asthma exacerbations or worsening events, visual analog scale (VAS) scores, immunological markers, and adverse events.

Results: Nine studies were included in the systematic review, seven of which contributed to the meta-analysis. SLIT was associated with fewer reported asthma exacerbations or worsening events than SCIT (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.09-0.89; moderate-certainty evidence). SCIT was associated with greater improvement in VAS scores (mean difference [MD], 1.80; 95% CI, 0.82-2.78; low-certainty evidence). No statistically significant differences were observed in the total rhinitis symptom score (TRSS; MD, 0.44; 95% CI, -0.14 to 1.02; very-low-certainty evidence), total medication score (TMS; MD, -0.48; 95% CI, -1.12 to 0.16; low-certainty evidence), or total asthma symptom score (TASS; MD, -0.24; 95% CI, -1.03 to 0.55; very-low-certainty evidence). No statistically significant differences were found in systemic reactions (OR, 0.28; 95% CI, 0.05-1.43), skin reactions (OR, 0.72; 95% CI, 0.41-1.28), nausea or vomiting (OR, 1.25; 95% CI, 0.23-6.94), or withdrawal rates (OR, 0.72; 95% CI, 0.21-2.51).

Conclusion: Limited comparative evidence suggests that SLIT may be associated with fewer reported asthma-worsening events than SCIT, whereas SCIT may be associated with greater improvement in VAS scores. However, these findings were based on a small number of clinically heterogeneous studies using nonstandardized outcome definitions. No clear differences were observed in rhinitis symptoms, medication use, asthma symptom scores, or most safety outcomes. Further high-quality head-to-head randomized controlled trials are needed.