Novel Therapeutics Development for Complex Chronic Rhinosinusitis

Download or read book Novel Therapeutics Development for Complex Chronic Rhinosinusitis written by Anastasios Maniakas and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Background: Chronic rhinosinusitis (CRS) is one of the most common chronic diseases in the developed world, with a significant proportion of patients remaining refractory to the standard of care treatment. This difficult-to-treat population is often left with few therapeutic options that provide low-morbidity, low-cost, and long-term meaningful symptomatologic improvement. Objectives: Evaluate the efficacy of a low-dose, long-term macrolide in a high-risk and carefully selected CRS population, refractory to appropriate medical (budesonide irrigations [BNI]) and surgical therapy (endoscopic sinus surgery [ESS]). Evaluate factors associated with treatment response following low-dose, long-term macrolide. Evaluate the effect of low-dose, long-term macrolide in modulating the sinonasal microbiome. Methodology: Patients at high-risk of disease recurrence following ESS+BNI were enrolled in a prospective clinical trial (Phase 1) at a tertiary care center. Serologic samples, microbial swabs, and patient-reported outcomes measures (PROM) were completed on the day of surgery (Visit-1) and four months postoperatively (Visit-2). Outcomes were evaluated using the Lund-Kennedy endoscopic score. If disease persisted on Visit-2, they were randomized (Phase 2) to receive 250gm azithromycin or a placebo three times per week for 16 weeks (Visit-3). Results: A total of 128 patients were enrolled in the Phase 1 prospective trial. At the first four-month follow-up, 48 patients showed disease persistence and were randomized to azithromycin or placebo. Overall, azithromycin did not show a statistically significant difference in disease clearance at Visit-3 compared to placebo (54% vs. 33%, respectively; p=0.146). When patients with aspirin-exacerbated respiratory disease (AERD) were excluded from the analysis, azithromycin showed a significant improvement in disease clearance compared to placebo (71% vs. 35%, respectively; p=0.031), with a number needed to treat of 3 (2.8). In a subgroup analysis looking at all patients with disease clearance, those on azithromycin reported significantly better PROM improvements than patients on placebo (p=0.046). Twenty patients received azithromycin in an open-label setting, either at Visit-2 or following failure of placebo, with 14 of 20 (70%) showing disease clearance. When analyzing the sinonasal microbiome, patients on azithromycin demonstrated a significant log-fold decrease in 29 different operational taxonomic units (OTUs) of Staphylococcus aureus compared to patients on placebo, while also showing a significant difference in beta diversity (p