Effectiveness of Dupilumab in the Treatment of Patients with Severe Uncontrolled CRSwNP: A "Real-Life" Observational Study in the First Year of Treatment

Abstract

The aim of this study was to evaluate the efficacy of dupilumab in the treatment of severe uncontrolled Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), with or without asthma as add-on therapy with intra-nasal corticosteroids in a real-life setting over the first year of treatment. Our data demonstrated that subcutaneous 300 mg dupilumab administered at home via a pre-filled auto-injector every two weeks, based on indications set by the Italian Medicines Agency, was rapidly effective in reducing the size of polyps, decreasing symptoms of disease, improving quality of life, and recovering olfaction. Significant improvement was observed after only 15 days of treatment, and it progressively increased at 6 and 12 months. Dupilumab was also effective in reducing the local nasal eosinophilic infiltrate, in decreasing the need for surgery and/or oral corticosteroids, and in improving control of associated comorbidities such as chronic eosinophilic otitis media and bronchial asthma. After 12 months of treatment, 96.5% of patients had a moderate/excellent response. From our data, it was evident that there was a group of patients that showed a very early response within one month of therapy, another group with early response within six months from baseline, and a last group that improved later within 12 months. The results of this study support the use of dupilumab as an effective option in the current standard of care for patients affected by severe uncontrolled CRSwNP.

Keywords: asthma; biologics; chronic rhinosinusitis with nasal polyps; dupilumab; eosinophilic otitis media; eosinophils; real life; treatment outcomes; type-2 inflammation.

Figure 1

NPS (left panel) and PNIF (right panel) mean value variations over time. (NPS: nasal polyp score; PNIF: peak nasal inspiratory flow; V0: visit at baseline; V1: 15 days of treatment; V2: 1 month visit; V3: 3-month visit; V4: 6-month visit; V6: 12-month visit).

Figure 2

SNOT-22 (left panel) and Sniffin’Sticks-16 Identification Test (right panel) over time. V0: visit at baseline; V1: 15 days of treatment; V2: 1 month; V3: 3 months of treatment; V4: 6 months of treatment; V6: 12 months of treatment).

Figure 3

Percentage of response according to EPOS 2020 criteria over the first year of treatment. V0: visit at baseline; V1: 15 days of treatment; V2: 1 months; V3: 3 months; V4: 6 months; V6: 12 months).

Figure 4

31-year-old male patient with medical history of multiple long-lasting cycles of OCS in the last 2 years (>60 cumulative days/year) and subsequent insulin-resistance and hyperglycemia; two previous surgeries with poor adherence to local corticosteroids. At baseline, the NPS was 5/8 (Rb: right side at baseline; Lb: left side at baseline). Fifteen days after the first administration of dupilumab, polyps were no longer visible (Rp: right side post therapy; Lp: left side post therapy).

Figure 5

61-year-old female patient with history of 6 previous surgeries, the last complicated with unilateral ophthalmoplegia and vision loss. At baseline, the NPS was 5/8 (Rb: right side at baseline; Lb: left side at baseline). After one month of therapy with dupilumab, the NPS decreased to 1/8 (Rp: right side post therapy; Lp: left side post therapy).

Figure 6

46-year-old male patient with medical history of 5 previous surgeries and persistent mixed neutrophilic eosinophilic infiltration at nasal cytology. Affected by severe OSAS and obesity, the patient was at increased anesthesiologic risk for a new surgery. At baseline, the NPS was 5/8 (Rb: right side at baseline; Lb: left side at baseline). After one month of therapy with dupilumab, polyps showed complete regression (Rp: right side post therapy; Lp: left side post therapy).