Rapid response to dupilumab in three type-2 inflammatory diseases
Published: March 5, 2022
Atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyps are diseases driven by type 2 inflammation and therefore often coexist in individual patients. Alleviation of patients’ distress and impairment early in the treatment process is considered an important therapeutic goal, and rapid relief of symptoms may increase the likelihood that patients will continue their treatment. Type-2 inflammatory diseases are responsive to treatment with dupilumab, which in phase 3 trials was effective after the first dose.
This analysis by Canonica et al., published in The Journal of Allergy and Clinical Immunology: In Practice, focused on responses to dupilumab within the first 2 weeks after administration. They took data from five, multinational phase 3 trials of dupilumab, conducted in more than 3,000 patients with moderate-to-severe atopic dermatitis inadequately controlled by topical treatment, uncontrolled moderate-to-severe asthma, or severe chronic rhinosinusitis with nasal polyps. In all three groups, symptoms were assessed before and after treatment. Atopic dermatitis symptoms were assessed by using the Eczema Area and Severity Index (EASI), a numerical rating scale for worst itch in any single day (daily peak pruritus score), and the Dermatology Life Quality Index (DLQI). Asthma improvement was assessed by measuring patients’ forced expiratory volume in 1 second (FEV1) before use of a bronchodilator and peak expiratory flow (PEF) (measures of lung function) and symptom score each morning. Patients with chronic rhinosinusitis and nasal polyps completed the University of Pennsylvania Smell Identification Test (UPSIT) and rated their nasal congestion or obstruction and loss of smell each day.
For the patients with atopic dermatitis, treatment with dupilumab resulted in a statistically significant and clinically meaningful response (defined as a ≥ 50% improvement in EASI score, a ≥ 3-point improvement in peak pruritus score, or a ≥ 4-point improvement in DLQI score) within 1 week for 48% of patients and within 2 weeks for almost 70%; by week 16, this increased to almost 80%. Improvement in itch began as early as day 2 and continued through the first 2 weeks of treatment, when there was a 20% difference between peak pruritus scores in the placebo and dupilumab treatment groups. For the patients with asthma, clinically meaningful responses were defined as increases from baseline of ≥ 100 mL and ≥ 200 mL in pre-bronchodilator FEV1. By week 2, more than 60% of patients had an increase ≥ 100 mL and almost 50% had an increase ≥ 200 mL. Overall, dupilumab treatment significantly increased patients’ pre-bronchodilator FEV1 by 280 mL by week 2. Patients with asthma also had significant improvements in their morning PEF by day 2 and their morning asthma symptoms by day 3. For patients with chronic rhinosinusitis and nasal polyps, more than half of those who received dupilumab had a clinically meaningful improvement (UPSIT score > 18) in their sense of smell by week 2. Dupilumab treatment also significantly improved loss of smell within 2 days and nasal congestion or obstruction within 1 day. For all three groups of patients, treatment effects further improved or were sustained to the end of the treatment periods of the respective studies. The authors concluded that treatment with dupilumab provides rapid (within 2 weeks after treatment initiation) clinically meaningful benefits in patients with moderate-to-severe atopic dermatitis, moderate-to-severe asthma, or severe chronic rhinosinusitis with nasal polyps.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.