Predictors of Refractory Primary Chronic Rhinosinusitis Following Endoscopic Sinus Surgery

ABSTRACT Background Refractory chronic rhinosinusitis (CRS) after functional endoscopic sinus surgery (FESS) has traditionally been defined by revision surgery alone. With the emergence of biologic therapies, treatment escalation now includes revision surgery and/or biologic initiation. We sought to identify independent predictors of refractory primary CRS using a composite outcome incorporating surgery and/or biologic initiation. Methods Adult patients with primary CRS undergoing FESS after 2015 were identified in the TriNetX Research Network. Patients with secondary CRS, prior biologic therapy, or sinonasal neoplasms were excluded. The primary outcome was refractory CRS, defined as revision FESS or biologic initiation from 3 months to 5 years postoperatively. Preoperative covariates were evaluated using Cox proportional hazards modeling with stepwise selection. Results Among 24,759 patients, 2866 (11.6%) had refractory CRS after FESS. Of these, 66.6% underwent revision FESS, 42.0% initiated biologic therapy, and 8.7% had revision surgery and initiated a biologic therapy. In multivariable analysis, asthma was the strongest predictor (HR 2.06, p < 0.001), followed by allergy to analgesic agents (e.g., NSAIDs) (HR 1.87, p < 0.001), nasal polyps (HR 1.67, p < 0.001), food allergy (HR 1.37, p = 0.096), COPD (HR 1.27, p = 0.006), eosinophilia (HR 1.27, p < 0.001), and Black or African American race (HR 1.16, p = 0.044). Conclusion Refractory CRS following FESS is strongly associated with type 2 inflammatory comorbidities and select demographic factors. Incorporating biologic therapy into outcome definitions provides a contemporary framework for risk stratification and postoperative counseling.