Dupilumab Linked With Significantly Improved Patient Outcomes in Severe Chronic Rhinosinusitis With Nasal Polyps

Patients with severe chronic rhinosinusitis with nasal polyps achieved significant improvements in health-related quality of life (HRQOL) and general health status with dupilumab treatment after 52 weeks.

Dupilumab was associated with significant improvements of health-related quality of life (HRQOL) and general health status in the treatment of patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP), according to study findings published this week in the European Journal of Allergy and Clinical Immunology.

Characterized as a predominantly type 2-mediated inflammatory disease of the nasal cavity and paranasal sinuses, CRSwNP has been associated with a high symptom burden and reduced HRQOL.

“HRQoL is a multidimensional dynamic concept that includes physical, mental, and social domains which are influenced by disease and treatment,” noted the study authors. “CRSwNP impacts multiple aspects of HRQoL including mental and physical health, sleep, productivity, cognitive and social functioning, and general health status.”

In the treatment of CRSwNP, the FDA-approved dupilumab, a fully human monoclonal antibody that blocks 2 key and central drivers of type 2 inflammation, interleukin (IL)-4 and IL-13, has been shown to be an effective therapeutic option.

Recent phase 3 findings of the SINUS-24 and SINUS-52 studies found significant improvement in patients with CRSwNP for endoscopic (nasal polyp score), radiologic (Lund-McKay computed tomography score), patient-reported symptoms, and clinical outcomes when treated with dupilumab on a background of intranasal corticosteroids.

The study authors conducted post-hoc analyses of the SINUS-24 and SINUS-52 trials to assess the effect of dupilumab on multidimensional disease-specific HRQOL and general health status measures in patients with severe CRSwNP, including difficult-to-treat subgroups. For the analyses, patients were randomized to dupilumab (n = 438) or placebo (n = 286) for 24 weeks (SINUS-24) or 52 weeks (SINUS-52).

Patients of the pooled intention-to-treat (ITT) population at week 24, week 52, and in the subgroups with/without asthma, non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD), and prior sinus surgery, were assessed for the primary outcomes of disease-specific HRQOL using 22-item sino-nasal outcome test (SNOT-22) and health status using EuroQoL-visual analog scale (EQ-VAS).

In the pooled ITT population at baseline, patients with CRSwNP exhibited poor disease-specific HRQOL (SNOT-22; mean [SD], 50.94 [20.66]) and general health status (EQ-VAS; mean [SD], 65.4 [20.4]), ​​with baseline domain scores being similar across subgroups. For all subgroups, “decreased sense of smell/taste” and “nasal blockage” were identified by patients as the most important SNOT-22 items affecting their health at baseline.

Compared with placebo, dupilumab was associated with significant improvements in the following assessed outcomes at 24 weeks:

  • SNOT-22 total (least-squares mean difference [LSMD], –36.6%; 95% CI, –41.9% to –31.3%)
  • SNOT-22 domain scores of nasal (LSMD, –1.16; 95% CI, –1.31 to –1.02), sleep (LSMD, –0.82; 95% CI, – 0.99 to –0.65), function (LSMD, –0.71; 95% CI, –0.87 to –0.56), emotion (LSMD, –0.66; 95% CI, –0.79 to –0.52), and ear/facial (LSDM, –0.60; 95% CI, – 0.72 to –0.48)
  • SNOT-22-item scores of “decreased sense of smell/taste” (LSMD, –1.97; 95% CI, –2.19 to –1.75; P < .0001) and “nasal blockage” (LSMD, –1.55; 95% CI, –1.75 to –1.36; P < .0001)

Moreover, significantly higher proportion of dupilumab-treated patients achieved a clinically meaningful improvement in EQ-VAS vs placebo at week 24 (46.8% vs 25.9%; OR, 2.58; 95% CI, 1.85-3.61; P < .0001) and week 52 (50.0% vs 18.3%; OR, 4.30; 95% CI, 2.55, 7.27; P < .0001).

Continued improvements were observed in the SINUS-52 cohort, with improvements occurring irrespective of comorbid asthma, NSAID-ERD, or prior surgery.

“The results provide stakeholders with insight into the significant impact this disease has on patient quality of life and the effects of dupilumab across multiple measures of HRQOL and overall health status,” concluded researchers.

Reference

Lee SE, Hopkins C, Mullol J, et al. Dupilumab improves health-related quality of life in severe chronic rhinosinusitis with nasal polyps. Allergy. Published online January 16, 2022. doi:10.1111/all.15222