Dupilumab improves CRSwNP outcomes across type 2 inflammation profiles

Key takeaways:

• Prevalence of type 2 inflammation ranged from 64.2% to 95.3% depending on the signature.
• Dupilumab’s efficacy is consistent with its profile as an inhibitor of IL-4 and IL-13 signaling.

Dupilumab improved outcomes among patients with severe chronic rhinosinusitis with nasal polyps across a range of type 2 inflammatory signatures, according to data presented at EAACI Hybrid Congress 2023 in Hamburg, Germany.

Treatment also reduced local and systemic type 2 inflammation biomarkers and was well tolerated, Claus Bachert, MD, PhD, department of otorhinolaryngology, head and neck surgery, University Hospital of Münster, said during his presentation.

The phase 3 multicenter, randomized, double-blind SINUS-24 (n = 276) and SINUS-52 (n = 448) studies involved patients with CRSwNP bilateral nasal polyp scores (NPS) of 5 or higher and nasal congestion (NC), as well as loss of smell (LOS) and/or rhinorrhea.

At week 24, both studies found significant improvements in NPS and NC with dupilumab (Dupixent, Sanofi Regeneron), in addition to significant improvements in sense of smell, total symptom score, and 22-item Sino-Nasal Outcome Test (SNOT-22) and Lund-Mackay computed tomography or LMK-CT scan scores.

Post-hoc analysis of these results examined the efficacy of 300 mg of dupilumab every 2 weeks through 24 weeks in SINUS-24 and 52 weeks in SINUS-52 based on six subgroups characterized by baseline type 2 signature definitions:

• 150 eosinophils/µL or higher, total IgE of 100 IU/mL or higher, or any coexisting type 2 condition such as asthma, atopic dermatitis and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease; 95.3% of patients;
• 150 eosinophils/µL or higher or total IgE of 100 IU/mL or higher; 92.3% of patients;
• 150 eosinophils/µL or higher (Global Initiative for Asthma guidelines); 85.8% of patients;
• 250 eosinophils/µL or higher or total IgE of 100 IU/mL or higher (European Position Paper on Rhinosinusitis and Nasal Polyps 2020); 83.4% of patients;
• asthma or 300 eosinophils/µL or greater (European Forum for Research and Education in Allergy and Airway Diseases); 76.4% of patients; and
• any coexisting type 2 condition; 64.2% of patients.

Dupilumab significantly improved NPS, NC, LOS and SNOT-22 scores compared with placebo across all six of the type 2 signature definitions, the researchers reported.

Patients on dupilumab had significantly greater odds for clinically meaningful improvements in NPS, MC, LOS and SNOT-22 scores compared with placebo across all six of the type 2 signature definitions as well.

Odds ratios for clinically meaningful improvements of 1 point or more for LOS, NC and LOS from baseline to week 24 in SINUS-24 across all six definitions (P < .0001 for all) included:

• NPS: 11.4 (95% CI, 7.4-17.5) to 14.9 (95% CI, 9.4-23.7);
• NC: 6.5 (95% CI, 4.5-9.3) to 9.6 (95% CI, 6-15.3); and
• LOS: 12.2 (95% CI, 8-18.8) to 17.8 (10.6-30).

At week 52, odds ratios for clinically meaningful improvements of 1 point or more for LOS, NC and LOS from baseline were similar or greater (P < .0001 for all), including:

• NPS: 18.95 (95% CI, 9.64-37.25) to 36.6 (95% CI, 13.7-97.8);
• NC: 7.6 (95% CI, 4.2-13.7) to 12.1 (95% CI, 5.8-25.4); and
• LOS: 9.2 (95% CI, 4.9-17.4) to 33.5 (95% CI, 11.3-99.8).

Odds ratios for clinically meaningful improvements in SNOT-22 scores of 8.9 points or higher ranged from 7.1 to 11 at week 52 (P < .0001) as well.

The researchers noted that these improvements are consistent with dupilumab’s profile as an inhibitor of IL-4 and IL-13 signaling, which they called key and central drivers of type 2 inflammation in chronic rhinosinusitis with nasal polyps.

Dupilumab was associated with significantly increased odds for clinically relevant responses compared with placebo among the patients who did not meet the criteria for type 2 inflammation as well, the researchers continued.