https://orcid.org/0000-0001-9305-6748
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Abstract
Introduction
Dupilumab is a monoclonal antibody targeting IL-4Rα recently licensed for severe asthma (SA). A Named Patients Program (NPP) was created in Italy before its commercial availability for SA patients with no other available therapeutic options. We aimed to assess the real-world effectiveness of dupilumab in patients with SA and unmet needs.
Methods
We performed a multicentre retrospective study, including SA patients admitted to the NPP treated with dupilumab for 12 months. Data on the number of exacerbations, Asthma Control Test (ACT), pre-bronchodilator FEV1%, oral corticosteroids (OCSs) use, FeNO and eosinophils count in peripheral blood were recorded at baseline and after 3, 6, and 12 months.
Results
We included 18 SA patients (mean age 53.3±12.4 years, 66.7% female). Eleven (61.1%) were OCSs dependent. Five patients (27.8%) received previous anti-IgE and/or anti-IL-5 agents. A significant improvement in ACT score (from 15.7±5.1 to 18.8±4.8, p=0.023), OCSs intake [10 (5–25) mg/day to 0 (0–5) mg/day, p=0.0333] and FeNO [from 25 (20–80) ppb to 21 (10.9–55.3) ppb, p=0.0190] was already detected after 3 months of treatment. After 12 months, a statistically significant decrease in the number of exacerbations from 2 (0–3) to 0 (0–1) (p<0.0068) and increase in FEV1% from 73.5±19.5% to 87.1±19.2% (p=0.0407) and ACT to a mean value of 22.4±1.7 (p<0.0001) and the interruption of OCSs in all the patients (p<0.0001) was observed. A transient increase in the eosinophil count was observed in five patients (above 1000 cells/μL in 2 cases) after 3 months, without any clinical effect.
Conclusion
Dupilumab improved all the explored clinical outcomes after 12 months, and the transient hypereosinophilia did not modify treatment response. These real-world data confirm the results reported in randomized controlled trials and provide an important opportunity to characterize the clinical impact of the treatment in a non-trial setting. Further real-world studies with a larger cohort of patients are needed to confirm these findings.
Abbreviations
SA, Severe Asthma; NPP, Named Patient Program; IL-4, Interleukin-4; IL-5, Interleukin-5; IL-13, Interleukin 13; CRSwNP, Chronic Rhinosinusitis with Nasal Polyps; CRSsNP, Chronic Rhinosinusitis without Nasal Polyps; AD, Atopic Dermatitis; GERD, Gastroesophageal Reflux Disease; BMI, Body Mass Index; ICS-LABA, Inhaled Corticosteroids – Long-Acting Beta-Agonist; LAMA, Long-Acting Muscarinic Antagonist; ACT, Asthma Control Test; MCID, Minimal Clinically Important Difference; FEV1, Forced expiratory volume in the 1st second; OCSs, Oral Corticosteroids (Prednisone); IgE, Immunoglobulin-E; FeNO, Fractional Exhaled Nitric Oxide.
Acknowledgments
The statistical analysis was designed and performed in collaboration with Filippo Palermo, Professor of Biostatistics at the University of Catania. Some of these data have been submitted in abstract form for a possible poster presentation at the virtual ERS International Congress 2021.
Author Contributions
All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data, took part in drafting the article or revising it critically for important intellectual content, agreed to submit to the current journal, gave final approval for the version to be published, and agreed to be accountable for all aspects of the work.
Disclosure
Prof. Dr. Alberto Papi reports grants from CHIESI, ASTRAZENECA, GSK, BI, PFIZER, TEVA, and SANOFI; personal fees from CHIESI, ASTRAZENECA, GSK, BI, MENARINI, NOVARTIS, ZAMBON, MUNDIPHARMA, TEVA, SANOFI, EDMOND PHARMA, IQVIA, MSD, AVILLION, and ELPEN PHARMACEUTICALS, outside the submitted work. The authors report no other conflicts of interest in this work.