Dornase alfa in stable neutrophilic asthma

SESSION TITLE: Asthma and Allergy SESSION TYPE: Original Investigations PRESENTED ON: 10/09/2023 08:30 am - 09:30 am PURPOSE: Neutrophilic asthma makes up to 50% of severe asthma cases, and therefore remains an area of great interest for directed therapies. Asthmatics have elevated levels of extracellular deoxyribonucleic acid (DNA) in sputum compared to healthy subjects. Nebulized recombinant human deoxyribonuclease (rhDNase, dornase alfa) randomly cleaves extracellular DNA released by airway neutrophils and other granulocytes, thereby reducing the viscosity of mucus. Benefits of dornase alfa are well-described in cystic fibrosis. Treatment with dornase alfa may be of benefit in stable neutrophilic asthma but has not been studied. In this pilot study, we studied neutrophilic asthmatics receiving 4 weeks of daily nebulized dornase alfa to assess safety profile of the study drug, as well as effect on lung function, symptom control (Asthma Control Test, ACT), and sputum characteristics and production. METHODS: This was an open label pilot study approved by our Institutional Review Board. We enrolled 19 adult asthma subjects (≥18 years). 4 subjects were ineligible due to screen failure after enrollment. The study design consisted of 3 visits. At Visit 1, participants underwent spirometry, ACT and sputum characteristic questionnaires, and sputum induction. Neutrophilic asthma was defined by sputum differential cell count of ≥40% neutrophils. Only those with defined sputum neutrophilia were enrolled in the therapeutic arm of the study. Neutrophilic asthmatics returned for Visits 2 and 3. At Visit 2, they received the first dose of nebulized dornase alfa. Nebulized dornase alfa was continued for total of 28-35 days. Participants returned for Visit 3 with repeat spirometry, ACT, sputum induction, and reported on sputum characteristics. RESULTS: A total of 15 subjects completed the study, 11 of whom were neutrophilic and 4 were non-neutrophilic. One neutrophilic subject was removed from analysis due to acute infection unrelated to the study. The study achieved its primary endpoint, which was assessing safety of the study drug. No subject withdrew from the study due to side effects from the study drug. There was not statistically significant improvement in lung function following 28 days of study drug. The median ACT improvement was 2 points (p=0.13). Sputum characteristic changes of neutrophilic asthmatics were notable with dornase alfa treatment. Ninety percent (9/10) noted it was easier to cough up sputum, and 80% (8/10) noted thinner mucus compared with baseline. CONCLUSIONS: This small pilot study of neutrophilic asthmatics showed safety in daily use of nebulized dornase alfa. A trend toward improved symptom control and notable improvement in ability to expectorate sputum due to thinner consistency was found with dornase alfa treatment. Further quantification of sputum characteristics was limited by a validated sputum questionnaire. CLINICAL IMPLICATIONS: Dornase alfa was associated with improved ability to expectorate and thickness of sputum in neutrophilic asthmatics in a stable state and may be a therapeutic option for these patients, but further study is needed. DISCLOSURES: Speaker/Speaker's Bureau relationship with Regeneron Please note: 04/11/22 - Current Added 04/15/2023 by Vamsi Guntur, source=Web Response, value=Honoraria Advisory Committee Member relationship with AstraZeneca Please note: 4/1/2021-Current Added 04/15/2023 by Vamsi Guntur, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with AstraZeneca Please note: March 2023 - Current Added 04/15/2023 by Vamsi Guntur, source=Web Response, value=Nothing yet No relevant relationships by Christena Kolakowski Advisory Committee Member relationship with GSK Please note: 11/16/2021-11/7/2023 Added 03/27/2023 by Laurie Manka, source=Web Response, value=Honoraria Consultant relationship with IngenioRx Please note: 1/31/2022-Pres Added 03/27/2023 by Laurie Manka, source=Web Response, value=Consulting fee No relevant relationships by Richard Martin No relevant relationships by Camille Moore No relevant relationships by Allen Stevens