Background: Smell impairment is more commonly related to chronic rhinosinusitis with nasal polyps (CRSwNP) than without, especially given associated asthma and/or NSAID-exacerbated respiratory disease and type 2 inflammation. Therapeutic options include intranasal and systemic corticosteroids, surgery and, more recently, biological therapy. We summarize current knowledge on the effect of biologics on olfaction in patients with CRSwNP.
Methods: We performed a systematic search of the PubMed and Cochrane databases from January 2001 to June 2022. Inclusion criteria were: adult patients with CRS treated with dupilumab, omalizumab, mepolizumab, benralizumab or reslizumab; studies published in English reporting outcomes in sense of smell using a psychophysical and/or subjective tools. Exclusion criteria covered reports that did not assess CRSwNP, smell loss evaluated with a different method according to mentioned inclusion criteria, review articles and expert opinion. No source of funding is available.
Results: Dupilumab has demonstrated rapid and sustained long-term improvement in smell in clinical trials and real-life. Omalizumab improves smell at 24w with a long-term maintenance but do not reach clinically relevant improvement. Mepolizumab and benralizumab improved smell at long-term measured with a subjective scale. No studies regarding the improvement of smell in patients with CRSwNP treated with reslizumab were found. Indirect comparisons by meta-analysis consistently conclude that dupilumab is the most effective biologic to improve the sense of smell. Conclusion: Dupilumab may have the highest efficacy in improving sense of smell, compared to omalizumab, mepolizumab and benralizumab.

Key words: Smell, Chronic rhinosinusitis with nasal polyps (CRSwNP), Dupilumab, Omalizumab, Mepolizumab, Benralizumab, Monoclonal antibodies