Dupilumab improves long‐term outcomes in patients with uncontrolled, moderate‐to‐severe GINA‐based type 2 asthma, irrespective of allergic status

Abstract

Background: Previous research has shown greater efficacy of dupilumab in patients with uncontrolled asthma and type 2 inflammation. We analyzed dupilumab's efficacy in patients from the TRAVERSE study with or without evidence of allergic asthma and type 2 inflammation per current GINA guidelines (≥150 eosinophils/μL or FeNO ≥20 ppb).Methods: All patients aged ≥12 years who rolled over from the placebo-controlled QUEST study (NCT02414854) to TRAVERSE (NCT02134028) received add-on dupilumab 300 mg every 2 weeks for up to 96 weeks. We assessed annualized severe asthma exacerbation rates (AERs) and changes from parent-study baseline (PSBL) in pre-bronchodilator FEV 1 and 5-item asthma control questionnaire (ACQ-5) score in patients with moderate-to-severe type 2 asthma with and without evidence of allergic asthma at PSBL. Results:In TRAVERSE, dupilumab consistently reduced AER across all subgroups.By Week 96, dupilumab increased pre-bronchodilator FEV 1 from PSBL by 0.35-0.41 L in patients receiving placebo during QUEST (placebo/dupilumab) and 0.34-0.44 L in those receiving dupilumab during QUEST (dupilumab/dupilumab) with an allergic phenotype at baseline. In patients without evidence of allergic asthma, prebronchodilator FEV 1 improved by 0.38-0.41 L and 0.33-0.37 L, respectively. By Week 48, ACQ-5 scores decreased from PSBL by 1.63-1.69 (placebo/dupilumab) and 1.74-1.81 (dupilumab/dupilumab) points across subgroups with allergic asthma, and 1.75-1.83 (placebo/dupilumab) and 1.78-1.86 (dupilumab/dupilumab) in those without. Conclusions:Long-term treatment with dupilumab reduced exacerbation rates and improved lung function and asthma control in patients with asthma with type 2 inflammation as per current GINA guidance and irrespective of evidence of allergic asthma.

Dupilumab Reduces Asthma Disease Burden and Recurrent SCS Use in Patients with CRSwNP and Coexisting Asthma

“…Another recent analysis of the SINUS population demonstrated dupilumab efficacy in patients with CRSwNP and coexisting asthma irrespective of the severity of their asthma at baseline, 13 while the TRAVERSE study demonstrated dupilumab efficacy in patients with Global Initiative for Asthma (GINA)-defined type 2 asthma and CRSwNP. 14 The efficacy of dupilumab in CRSwNP and asthma may be explained by its mechanism of action in targeting IL-4 and IL-13, which are key drivers of type 2 inflammation in both diseases, 5,6 with more than 95% of the overall SINUS population having type 2 inflammatory disease on the basis of a range of biomarkers and clinical measures. 15 Limitations of this analysis include its post hoc nature and the categorization of patients with asthma on the basis of selfreporting by the study participants.…”

The origins and longevity of IgE responses as indicated by serological and cellular studies in mice and humans

“…Individuals with high IgE at baseline in several diseases show clinical benefit with anti‐IL‐4Rα (dupilumab) treatment, for example, in alopecia areata, allergic asthma, and atopic dermatitis. 163 , 164 , 165 , 166 Dupilumab causes downmodulation and internalization of IL4Rα 167 to interfere with the IL‐4 signaling that is an absolute requirement for IgE CSR. 106 While dupilumab might affect additional aspects of atopic disease, 168 , 169 , 170 dupilumab leads to a 20%–50% drop in serum IgE over several months, 166 , 171 , 172 , 173 , 174 and >80% loss over treatment periods of 1 year or more 175 , 176 , 177 , 178 in allergic asthma, allergic rhinitis with or without nasal polyps, and atopic dermatitis patients, which fits with the notion that most IgE + ASC are short‐lived cells in these diseases.…”