Reducing nasal commensal viruses with a ribavirin nasal spray may improve symptoms in patients with allergic rhinitis, according to findings from a phase 2 randomized clinical trial. Parallel laboratory studies suggested that nasal commensal viruses may contribute to allergic rhinitis through activation of type I interferon signaling and downstream inflammatory pathways.
In the randomized, double-blind, placebo-controlled, single-center phase 2 trial, researchers assigned 42 patients with allergic rhinitis to receive ribavirin nasal spray (22 patients) or placebo (20 patients) twice daily for 4 weeks. The primary endpoint was the Total Nasal Symptom Score . Secondary endpoints included the Visual Analog Scale, Rhinitis Control Assessment Test, safety, and exploratory analyses of nasal commensal viruses, inflammatory cytokines, and neutrophil extracellular trap activity. Parallel mechanistic studies were conducted in mouse models of allergic rhinitis to investigate the biologic effects of reducing nasal commensal viruses.
Compared with placebo, ribavirin treatment resulted in lower otal Nasal Symptom Score after 4 weeks of therapy. Improvements were also observed in Visual Analog Scale and Rhinitis Control Assessment Test scores. Exploratory analyses showed that ribavirin reduced nasal commensal virus abundance, whereas viral abundance remained largely unchanged in the placebo group. No grade 3 or higher adverse events, serious adverse events, or adverse drug reactions were reported during the study.
Metatranscriptomic analyses showed that patients with allergic rhinitis had higher nasal commensal virus abundance than healthy controls. Viral abundance correlated with symptom severity and interferon-stimulated gene expression. Exploratory subgroup analyses suggested that patients with higher baseline viral abundance or more severe allergic rhinitis symptoms experienced greater improvement following ribavirin treatment. One-year follow-up also suggested lower symptom scores and reduced use of allergic rhinitis medications among patients who received ribavirin compared with placebo, although these findings were exploratory.
Laboratory studies supported a potential mechanism for these clinical findings. In mouse models, reducing nasal commensal viruses with ribavirin decreased sneezing and scratching behavior, eosinophilic inflammation, type II cytokine production, and nasal mucosal injury. Single-cell RNA sequencing demonstrated reduced recruitment of interferon-induced neutrophil subsets following antiviral treatment. Additional experiments suggested that nasal commensal viruses activate innate immune sensors, triggering type I interferon production, neutrophil extracellular trap formation, and allergic inflammation.
The researchers noted several limitations. The clinical trial was a small, single-center phase 2 study that requires confirmation in larger, multicenter phase 3 trials. In addition, much of the mechanistic evidence was derived from mouse models, and the specific nasal commensal viruses identified in exploratory analyses have not been established as causal drivers of allergic rhinitis in humans. The authors also noted that the effectiveness and safety of ribavirin spray remain exploratory and require validation across broader patient populations and allergen profiles.
Overall, the findings suggest that reducing nasal commensal viruses may represent a novel therapeutic strategy for allergic rhinitis, although larger clinical studies will be needed to determine whether this approach translates into routine clinical practice. "Our basic and clinical data suggest that the reduction of nasal commensal viruses using antiviral drugs may be effective in AR therapy," wrote lead study author Ye Zhou, of the National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China, and colleagues.
Disclosures: The authors reported no competing interests. Xuetao Cao is an associate editor of Signal Transduction and Targeted Therapy but was not involved in the editorial handling of the manuscript.