Biologic Agents for the Treatment of Chronic Rhinosinusitis With Nasal Polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis is a complex inflammatory disorder, which is often recalcitrant to medical and surgical management. Recently, biologic agents have been studied as an adjunct treatment for this patient population. OBJECTIVE: The purpose of this study is to examine the role of biologic agents for chronic rhinosinusitis patients by reviewing literature and clinical trials. METHODS: A comprehensive review of literature and clinical trials-both recently completed and ongoing-was undertaken to examine up-to-date evidence of current biologic therapy and its role in chronic rhinosinusitis patients-including anti-IgE, anti-IL-4, anti-IL-5, anti-IL-13, and GATA-3 DNAzyme. RESULTS: Specific biologic agents discussed include omalizumab, reslizumab, mepolizumab, benralizumab, dupilumab, and Hgd40/SB010. Risks, side effects, and administration information are also reviewed. An algorithm for the use of biologics in patients with chronic rhinosinusitis with nasal polyposis is proposed. CONCLUSION: These treatments have promising results and may prove to be an important adjunct for patients with recalcitrant sinus disease.

Biodistribution of the GATA-3-specific DNAzyme hgd40 after inhalative exposure in mice, rats and dogs.

The DNAzyme hgd40 was shown to effectively reduce expression of the transcription factor GATA-3 RNA which plays an important role in the regulation of Th2-mediated immune mechanisms such as in allergic bronchial asthma. However, uptake, biodistribution and pharmacokinetics of hgd40 have not been investigated yet. We examined local and systemic distribution of hgd40 in naive mice and mice suffering from experimental asthma. Furthermore, we evaluated the pharmacokinetics as a function of dose following single and repeated administration in rats and dogs. Using intranasal administration of fluorescently labeled hgd40 we demonstrated that the DNAzyme was evenly distributed in inflamed asthmatic mouse lungs within minutes after single dose application. Systemic distribution was investigated in mice using radioactive labeled hgd40. After intratracheal application, highest amounts of hgd40 were detected in the lungs. High amounts were also detected in the bladder indicating urinary excretion as a major elimination pathway. In serum, low systemic hgd40 levels were detected already at 5 min post application (p.a.), subsequently decreasing over time to non-detectable levels at 2h p.a. As revealed by Single Photon Emission Computed Tomography, trace amounts of hgd40 were detectable in lungs up to 7 days p.a. Also in the toxicologically relevant rats and dogs, hgd40 was detectable in blood only shortly after inhalative application. The plasma pharmacokinetic profile was dose and time dependent. Repeated administration did not lead to drug accumulation in plasma of dogs and rats. These pharmacokinetic of hgd40 provide guidance for clinical development, and support an infrequent and convenient dose administration regimen.