{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T09:25:21Z","timestamp":1787217921543,"version":"build-2736575974"},"reference-count":28,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: Real-world evidence on dupilumab-induced clinical remission on treatment and on the predictors of complete response in severe uncontrolled asthma (SUA) is still limited. Methods: We conducted a single-centre ambispective uncontrolled observational study including 152 adults with SUA who started dupilumab. Lung function, type-2 (T2) biomarkers, patient-reported outcomes, exacerbations, oral corticosteroid (OCS) use, emergency-department (ED) visits and hospitalisations were compared between baseline and last follow-up. Response was graded with FEOS and EXACTO. Independent predictors of complete response (EXACTO = 1) were explored by multivariable logistic regression. Results: Mean age was 50 \u00b1 12 years, 67.1% were women, baseline FEV1 was 82 \u00b1 22% predicted, blood eosinophils were 612 \u00b1 577 cells\/\u00b5L and FeNO was 55 \u00b1 46 ppb. After 21 \u00b1 8 months, ACT improved from 15.7 to 23.3, ACQ-5 from 4.0 to 0.35, mini-AQLQ from 2.18 to 4.53, SNOT-22 from 52 to 16, and FEV1 by 275 \u00b1 180 mL (all p &lt; 0.001). Annual exacerbations decreased from 7.9 to 0.7, ED visits from 3.17 to 0.28, hospitalisations from 0.71 to 0.08, and maintenance OCS use from 11.8% to 3.9%. According to EXACTO, 95 patients (62.5%) achieved complete response\/super-response. Independent predictors were higher baseline FEV1, higher eosinophil count, allergic rhinitis, rhinosinusitis with nasal polyps and atopic dermatitis, whereas prior OCS bursts and higher FeNO were inversely associated. Model discrimination was adequate (AUC = 0.91). Conclusions: Dupilumab achieved clinical remission on treatment in almost two-thirds of patients with SUA and markedly reduced healthcare utilisation. A T2-comorbidity-rich profile identified patients with the highest probability of complete response.<\/jats:p>","DOI":"10.3390\/jcm15166429","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T08:10:20Z","timestamp":1787213420000},"page":"6429","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real-World Effectiveness of Dupilumab in Severe Uncontrolled Asthma: Clinical Remission on Treatment, Predictors of Complete Response and Impact on Type-2 Comorbidities"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3374-4623","authenticated-orcid":false,"given":"Eusebi","family":"Chiner","sequence":"first","affiliation":[{"name":"Pneumology Department, San Juan de Alicante University Hospital, Ctra N-332, s\/n, 03550 San Juan de Alicante, Alicante, Spain"},{"name":"Department of Clinical Medicine, Miguel Hern\u00e1ndez University, 03202 Elche, Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8225-3623","authenticated-orcid":false,"given":"Ignacio","family":"Boira","sequence":"additional","affiliation":[{"name":"Pneumology Department, San Juan de Alicante University Hospital, Ctra N-332, s\/n, 03550 San Juan de Alicante, Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Ant\u00f3n","sequence":"additional","affiliation":[{"name":"Allergy Department, San Juan de Alicante University Hospital, 03550 San Juan de Alicante, Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0984-1888","authenticated-orcid":false,"given":"Mar\u00eda \u00c1ngeles","family":"Bernabeu","sequence":"additional","affiliation":[{"name":"Pharmacy Department, San Juan de Alicante University Hospital, 03550 San Juan de Alicante, Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Luis","family":"Lafuente","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology Department, San Juan de Alicante University Hospital, 03550 San Juan de Alicante, Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Pignatelli","sequence":"additional","affiliation":[{"name":"Pneumology Department, San Juan de Alicante University Hospital, Ctra N-332, s\/n, 03550 San Juan de Alicante, Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1801-7211","authenticated-orcid":false,"given":"Pilar","family":"Soro","sequence":"additional","affiliation":[{"name":"Dermatology Department, San Juan de Alicante University Hospital, 03550 San Juan de Alicante, Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3836-5884","authenticated-orcid":false,"given":"Violeta","family":"Esteban","sequence":"additional","affiliation":[{"name":"Pneumology Department, San Juan de Alicante University Hospital, Ctra N-332, s\/n, 03550 San Juan de Alicante, Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1921-0361","authenticated-orcid":false,"given":"Paula","family":"Fern\u00e1ndez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Pneumology Department, San Juan de Alicante University Hospital, Ctra N-332, s\/n, 03550 San Juan de Alicante, Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anays","family":"Mart\u00ednez-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Pneumology Department, San Juan de Alicante University Hospital, Ctra N-332, s\/n, 03550 San Juan de Alicante, Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","unstructured":"Global Initiative for Asthma (GINA) (2026, June 06). Global Strategy for Asthma Management and Prevention. Available online: https:\/\/ginasthma.org."},{"key":"ref_2","unstructured":"GEMA 5.5 Working Group (2025). Gu\u00eda Espa\u00f1ola Para el Manejo del Asma (GEMA 5.5) [Spanish Guideline on the Management of Asthma], SANED. Available online: https:\/\/www.gemasma.com."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100486","DOI":"10.1016\/j.opresp.2025.100486","article-title":"Documento de consenso de asma grave. Actualizaci\u00f3n 2025","volume":"7","author":"Plaza","year":"2025","journal-title":"Open Respir. Arch."},{"key":"ref_4","first-page":"466","article-title":"Prevalence of uncontrolled severe persistent asthma in pneumology and allergy hospital units in Spain","volume":"21","author":"Quirce","year":"2011","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1080\/02770903.2018.1499035","article-title":"Economic impact of severe asthma in Spain: Multicentre observational longitudinal study","volume":"56","author":"Quirce","year":"2019","journal-title":"J. Asthma"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1111\/all.15889","article-title":"Nomenclature of allergic diseases and hypersensitivity reactions: Adapted to modern needs: An EAACI position paper","volume":"78","author":"Jutel","year":"2023","journal-title":"Allergy"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"240088","DOI":"10.1183\/16000617.0088-2024","article-title":"Biologics in severe asthma: A state-of-the-art review","volume":"34","author":"Gyawali","year":"2025","journal-title":"Eur. Respir. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.jaci.2005.07.011","article-title":"Airway remodeling contributes to the progressive loss of lung function in asthma: An overview","volume":"116","author":"Pascual","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.arbres.2023.05.014","article-title":"Validation of a Pathological Score for the Assessment of Bronchial Biopsies in Severe Uncontrolled Asthma","volume":"59","author":"Cosio","year":"2023","journal-title":"Arch. Bronconeumol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1056\/NEJMoa1804092","article-title":"Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma (LIBERTY ASTHMA QUEST)","volume":"378","author":"Castro","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1056\/NEJMoa1804093","article-title":"Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma (LIBERTY ASTHMA VENTURE)","volume":"378","author":"Rabe","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1016\/S0140-6736(17)31191-1","article-title":"Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS)","volume":"389","author":"Blauvelt","year":"2017","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1016\/S0140-6736(19)31881-1","article-title":"Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (SINUS-24 and SINUS-52)","volume":"394","author":"Bachert","year":"2019","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1056\/NEJMoa2205982","article-title":"Dupilumab in adults and adolescents with eosinophilic esophagitis","volume":"387","author":"Dellon","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1056\/NEJMoa2303951","article-title":"Dupilumab for COPD with type 2 inflammation indicated by eosinophil counts (BOREAS)","volume":"389","author":"Bhatt","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.1056\/NEJMoa2401304","article-title":"Dupilumab for COPD with blood eosinophil evidence of type 2 inflammation (NOTUS)","volume":"390","author":"Bhatt","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1164\/rccm.201904-0903SO","article-title":"Systematic literature review of systemic corticosteroid use for asthma management","volume":"201","author":"Bleecker","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1900804","DOI":"10.1183\/13993003.00804-2019","article-title":"Increased mortality in patients with corticosteroid-dependent asthma: A nationwide population-based study","volume":"54","author":"Lee","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1016\/j.jaip.2021.01.033","article-title":"Development of a Tool to Measure the Clinical Response to Biologic Therapy in Uncontrolled Severe Asthma: The FEV1, Exacerbations, Oral Corticosteroids, Symptoms Score","volume":"9","author":"Almonacid","year":"2021","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_20","first-page":"1","article-title":"Response to Monoclonal Antibodies in Asthma: Definitions, Potential Reasons for Failure, and Therapeutic Options for Suboptimal Response","volume":"33","author":"Cisneros","year":"2023","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Garc\u00eda, R., Gimeno Perib\u00e1\u00f1ez, M.A., Albi Rodr\u00edguez, M.S., Almonacid S\u00e1nchez, C., Alsina Restoy, X., Aguirre-Franco, C.E., Bala\u00f1\u00e1 Corber\u00f3, A., Chiner, E., D\u00edaz L\u00f3pez, M., and Fern\u00e1ndez \u00c1lvarez, R. (2026). Recommendations for Performing Spirometry. Arch. Bronconeumol., S0300-2896(26)00012-8.","DOI":"10.1016\/j.arbres.2025.12.016"},{"key":"ref_22","unstructured":"Romero, A. (2017). Cuestionarios para medir el control del asma. Manual SEPAR n\u00ba34, Respira-Fundaci\u00f3n Espa\u00f1ola del Pulm\u00f3n-SEPAR."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1111\/cea.13614","article-title":"Effectiveness and safety of dupilumab for the treatment of severe asthma in a real-life French multi-centre adult cohort","volume":"50","author":"Dupin","year":"2020","journal-title":"Clin. Exp. Allergy"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"219","DOI":"10.4168\/aair.2021.13.2.219","article-title":"Sex Differences in Severe Asthma: Results from Severe Asthma Network in Italy-SANI","volume":"13","author":"Senna","year":"2021","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S2213-2600(24)00293-5","article-title":"Clinical remission attainment, definitions, and correlates among patients with severe asthma treated with biologics: A systematic review and meta-analysis","volume":"13","author":"Shackleford","year":"2025","journal-title":"Lancet Respir. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.chest.2019.10.053","article-title":"Characterization of severe asthma worldwide: Data from the International Severe Asthma Registry (ISAR)","volume":"157","author":"Wang","year":"2020","journal-title":"Chest"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0140-6736(23)02284-5","article-title":"Reduction of daily maintenance inhaled corticosteroids in patients with severe eosinophilic asthma treated with benralizumab (SHAMAL)","volume":"403","author":"Jackson","year":"2024","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1164\/rccm.202311-2192OC","article-title":"Exploring Definitions and Predictors of Severe Asthma Clinical Remission after Biologic Treatment in Adults","volume":"210","author":"Scelo","year":"2024","journal-title":"Am. J. Respir. Crit. Care Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/16\/6429\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T08:43:44Z","timestamp":1787215424000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/16\/6429"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":28,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["jcm15166429"],"URL":"https:\/\/doi.org\/10.3390\/jcm15166429","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]}}}