Dupilumab improves CRSwNP outcomes despite severity of baseline loss of smell
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LOUISVILLE, Ky. — Dupilumab improved symptoms among patients with chronic rhinosinusitis with nasal polyps regardless of baseline severity of smell loss, according to study results.
CRSwNP is associated with a high symptom burden and poor health-related quality of life, according to Zachary M. Soler, MD, MSc, professor in the department of otolaryngology, head and neck surgery at Medical University of South Carolina, and colleagues. Smell loss correlates with disease severity and is one of its cardinal symptoms, with a significant detrimental impact on quality of life, the researchers continued.
In a study presented at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting, the researchers conducted a post-hoc analysis of the phase 3 SINUS-24 and SINUS-52 studies of 724 patients with severe CRSwNP assigned 300 mg of dupilumab (Dupixent, Sanofi Genzyme/Regeneron) or placebo every 2 weeks.
Researchers categorized patients according to their baseline daily self-reported loss-of-smell score, with 0 representing no symptoms, 1 for mild symptoms, 2 for moderate symptoms and 3 indicating severe symptoms. Also, researchers assessed patients’ nasal polyp score (NPS), nasal congestion or obstruction and 22-item sino-nasal outcome test scores.
Nearly all the patients, 97.7%, had a loss-of-smell score greater than 1 at baseline, with 83% having a score greater than 2. The patients with severe loss of smell at baseline had greater incidence of prior surgery, asthma and nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (AERD-ERD) than those with moderate loss of smell as well.
“The presence of prior surgery, asthma or AERD-ERD each increases the odds of having severe vs. moderate loss of smell,” Soler said during his presentation.
Specific odds ratios for severe loss of smell at baseline included 3.01 (95% CI, 1.97-4.59) for prior surgery, 1.72 (95% CI, 1.35-2.18) for each additional prior surgery, 2.62 (95% CI, 1.72-4) for asthma history and 2.5 (95% CI, 1.43-4.38) for AERD-ERD history.
Moreover, odds of severe vs. moderate loss of smell increased with each one-point increase in the severity of patient-reported nasal congestion score (OR = 6.01; 95% CI, 3.95-9.15) and SNOT-22 score (OR = 1.03; 95% CI, 1.02-1.05).
Overall, compared with those patients on placebo, the patients assigned dupilumab experienced significant improvements in NPS, nasal congestion or obstruction and SNOT-22 scores regardless of whether they had moderate or severe loss of smell at baseline, the researchers found.
Patients with moderate baseline loss of smell (n = 106) reported least-square mean changes from baseline in nasal polyp score of –1 (95% CI, –1.53 to –0.47) at week 8 and –1.9 (95% CI, –2.56 to –1.25; P < .001 for both) at week 24 with dupilumab vs. placebo.
Those with severe baseline loss of smell (n = 601) reported least-square mean changes from baseline in nasal polyp score of –1.38 (95% CI, –1.6 to –1.15) at week 8 and –1.95 (95% CI, –2.2 to –1.7; P < .001 for both) at week 24.
Nasal congestion score least-square mean changes from baseline increased from weeks 4 to 24, from –0.16 (95% CI, –32 to 0) to –0.35 (95% CI, –0.64 to –0.06; P < .05) for those with moderate baseline loss of smell and from –0.44 (95% CI, –0.52 to –0.36) to –1 (95% CI, –1.13 to –0.87; P < .001 for both) for those with severe baseline loss of smell.
Finally, least-square mean changes from baseline in SNOT-22 scores included –8.8 (95% CI, –15 to –2.5; P < .01) at week 8 and –7.5 (95% CI, –14.6 to –0.5; P < .05) for patients with baseline moderate loss of smell, with corresponding changes of –16.6 (95% CI, –19.5 to –13.8; P < .001) and –21.7 (95% CI, –24.6 to –18.8; P < .001) for those with severe loss of smell.
“The magnitude of improvements with dupilumab were numerically greater in patients with severe vs. moderate baseline loss of smell, and improvements at the first post-baseline assessment were sustained or increased at week 24 irrespective of baseline loss of smell,” Soler said.
Based on these findings, the researchers concluded that there is an association between greater severity of loss of smell and greater disease burden in CRSwNP and that dupilumab significantly improved outcomes and health-related quality of life despite baseline severity of smell loss.