Researchers Link Smell Loss, Disease Burden, and Dupilumab Efficacy in CRSwNP

Greater disease burden in chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with increased loss of smell severity. Outcomes of CRSwNP were significantly improved with dupilumab, regardless of loss of smell severity at baseline. These are among the post-hoc analysis findings presented at the American College of Allergy, Asthma & Immunology (ACAAI) 2022 Annual Scientific Meeting, held from November 10 to 14, in Louisville, Kentucky.

Investigators sought to assess the association between smell loss (at baseline) and other disease aspects in CRSwNP, and to evaluate dupilumab effects according to severity of smell loss (at baseline). Endpoints included patient-reported nasal congestion/obstruction (NC), measured on a scale of 0 to 3; symptoms as measured via a 22-item sinonasal outcome test (SNOT-22), which uses a 0 to 110 scoring system; and nasal polyp score (NPS), using a 0 to 8 scale.

Investigators conducted a post-hoc analysis of pooled data from the SINUS-24 (ClinicalTrials.gov Identifier: NCT02912468) and SINUS-52 (ClinicalTrials.gov Identifier: NCT02898454) trials. They evaluated dupilumab effects in these studies according to severity of baseline monthly average patient-reported loss of smell (LoS), measured on a scale of 0 to 3 (moderate LoS = more than 1 and up to 2; severe LoS = more than 2 and up to 3). Analysis included 724 patients randomly assigned to receive either dupilumab 300 mg or placebo every 2 weeks.

At baseline, 601 patients (83%) reported severe LoS and 106 patients (15%) reported moderate LoS. Investigators also calculated odds ratios for severe vs moderate LoS at baseline (OR, 1.12; 95% CI, 0.96-1.32); with 1-point increase in NPS (OR, 6.01; 95% CI, 3.95-9.15); with 1-point increase in NC (OR, 1.03; 95% CI, 1.02-1.05); and with 1-point increase in SNOT-22 (OR, 3.01; 95% CI, 1.97-4.59), for with vs without prior sinonasal surgery.

Investigators then calculated least squares mean differences (LSMD) in symptom scores at week 24 for the dupilumab vs placebo groups in change from baseline. These endpoints were calculated by symptom score for those with moderate baseline LoS (NPS, -1.90; 95% CI, -2.56 to -1.25; NC, -0.35; 95% CI, -0.64 to -0.06; SNOT-22, -7.52; 95% CI, -14.55 to -0.48) and for those with severe baseline LoS (NPS, -1.95; 95% CI, -2.20 to -1.70; NC, -1.00; 95% CI, -1.13 to -0.87; SNOT-22, -21.72; 95% CI, -24.63 to -18.82) (all P <.05).

Investigators concluded “Increased severity of loss of smell is associated with greater disease burden in CRSwNP. Dupilumab significantly improved outcomes and HRQoL regardless of baseline severity of smell loss.”