{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:44:57Z","timestamp":1791398697851,"version":"4.3.3"},"reference-count":21,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Severe asthma remains associated with substantial morbidity despite optimized inhaled therapy. Biologic agents targeting type 2 inflammation improve clinical outcomes; however, real-world evidence regarding the durability of these effects beyond the first treatment year remains limited. The present study extends the follow-up of a previously reported real-world cohort in which 12-month outcomes of biologic therapy were evaluated. Methods: We conducted a retrospective observational longitudinal study of adults with severe asthma treated with omalizumab, benralizumab, or dupilumab at a tertiary center in T\u00e2rgu-Mure\u0219, Romania, between 2020 and 2025, extending follow-up of a previously published real-world cohort. The same patient cohort was followed for an additional period, with longitudinal data collected up to 24 months after biologic therapy initiation. Clinical, functional, and biomarker outcomes were assessed at baseline, 12 months, and 24 months, including Asthma Control Test (ACT) score, forced expiratory volume in one second (FEV1% predicted), annual exacerbation rate, blood eosinophil count, and fractional exhaled nitric oxide (FeNO). Remission was defined as clinical (ACT \u2265 20, no severe exacerbations, and no maintenance oral corticosteroids), biological (FeNO &lt; 20 ppb and blood eosinophils &lt; 150\/\u00b5L), and complete (both clinical and biological). Longitudinal changes were analyzed using the Friedman test with post hoc Wilcoxon signed-rank tests. Results: Forty-eight patients were included at baseline, and 41 had available data at 24 months. ACT scores improved from 12 (IQR 11\u201314) at baseline to 23 (21\u201325) at 12 months and remained stable at 22 (20\u201325) at 24 months (p &lt; 0.001). Predicted FEV1% increased from 50 (39\u201359) to 78 (68\u201388) at 12 months and 79 (66\u201396) at 24 months (p &lt; 0.001). Blood eosinophil counts were markedly suppressed, and FeNO levels continued to decrease over time. Exacerbations declined from 2 (2\u20133) per year at baseline to 0 and 0.5 (0\u20131) at 12 and 24 months, respectively (p &lt; 0.001). At 24 months, clinical, biological, and complete remission were observed in 61.0%, 78.0%, and 41.5% of patients with available paired data, respectively. Conclusions: Biologic therapy was associated with sustained clinical and functional improvement over 24 months, accompanied by sustained improvement in type 2 airway inflammation and increasing proportions of patients meeting remission criteria in real-world practice.<\/jats:p>","DOI":"10.3390\/jcm15062444","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T09:48:42Z","timestamp":1774259322000},"page":"2444","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Long-Term Clinical and Biological Outcomes of Biologic Therapy in Severe Asthma: 24-Month Real-World Cohort Study from Romania"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9439-0590","authenticated-orcid":false,"given":"Corina","family":"M\u0103rginean","sequence":"first","affiliation":[{"name":"Oncology and Palliative Care Department, George Emil Palade University of Medicine, Pharmacy, Science and Technology of T\u00e2rgu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea Cristina","family":"Safta","sequence":"additional","affiliation":[{"name":"Pulmonology Clinic, Mures County Clinical Hospital, 540011 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0882-870X","authenticated-orcid":false,"given":"Drago\u0219","family":"Hu\u021banu","sequence":"additional","affiliation":[{"name":"Pulmonology Department, George Emil Palade University of Medicine, Pharmacy, Science and Technology of T\u00e2rgu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7785-0121","authenticated-orcid":false,"given":"Corina Eugenia","family":"Budin","sequence":"additional","affiliation":[{"name":"Pathophysiology Department, George Emil Palade University of Medicine, Pharmacy, Science and Technology of T\u00e2rgu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7910-0123","authenticated-orcid":false,"given":"Maria Beatrice","family":"Ianosi","sequence":"additional","affiliation":[{"name":"Pulmonology Clinic, Mures County Clinical Hospital, 540011 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1990-6767","authenticated-orcid":false,"given":"Gabriela","family":"Jimborean","sequence":"additional","affiliation":[{"name":"Pulmonology Department, George Emil Palade University of Medicine, Pharmacy, Science and Technology of T\u00e2rgu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3558-2856","authenticated-orcid":false,"given":"Edith-Simona","family":"Ianosi","sequence":"additional","affiliation":[{"name":"Pulmonology Department, George Emil Palade University of Medicine, Pharmacy, Science and Technology of T\u00e2rgu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"ref_1","unstructured":"Global Initiative for Asthma\u2014GINA (2025, March 15). 2024 GINA Main Report. Available online: https:\/\/ginasthma.org\/2024-report\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1056\/NEJMra2032506","article-title":"Biologic Therapies for Severe Asthma","volume":"386","author":"Brusselle","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/S2213-2600(24)00304-7","article-title":"Asthma remission: A call for a globally standardised definition","volume":"13","author":"Lommatzsch","year":"2025","journal-title":"Lancet Respir. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2102583","DOI":"10.1183\/13993003.02583-2021","article-title":"Asthma Remission: What Is It and How Can It Be Achieved?","volume":"60","author":"Thomas","year":"2022","journal-title":"Eur. Respir. J."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kayser, M.Z., S\u00fchling, H., Fuge, J., Hinze, C.A., Drick, N., Kneidinger, N., Behr, J., Taube, C., Welte, T., and Haasler, I. (2024). Long-term multicenter comparison shows equivalent efficacy of monoclonal antibodies in severe asthma therapy. BMC Pulm. Med., 24.","DOI":"10.1186\/s12890-024-02964-4"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/S2213-2600(23)00415-0","article-title":"Pioneering a paradigm shift in asthma management: Remission as a treatment goal","volume":"12","author":"Lommatzsch","year":"2024","journal-title":"Lancet Respir. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1016\/S0140-6736(22)00331-2","article-title":"Disease-modifying anti-asthmatic drugs","volume":"399","author":"Lommatzsch","year":"2022","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1097\/MCP.0000000000001067","article-title":"Long-term safety, durability of response, cessation and switching of biologics","volume":"30","author":"Mohan","year":"2024","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.arbres.2025.04.003","article-title":"Early Failure, Late Failure, and Sustained Response to Biologics in Severe Asthma: A Long-term, Real-world, Multicentre Study","volume":"61","author":"Plaza","year":"2025","journal-title":"Arch. Bronconeumol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1016\/j.jaip.2025.05.031","article-title":"How to Adjust Asthma Management Once Asthma Is Controlled on Long-Term Biologic Therapy","volume":"13","author":"Wechsler","year":"2025","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"M\u0103rginean, C., Hu\u021banu, D., Vultur, M.A., S\u00e1rk\u00f6zi, H.-K., Iano\u0219i, E.-S., Iano\u0219i, M.B., Safta, A., Jimborean, G., and Budin, C.E. (2025). Is Biologic Therapy an Effective Tool for Achieving Remission in Severe Asthma? A Retrospective Study in Central Romania. Life, 15.","DOI":"10.3390\/life15071113"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kardas, G., Kuna, P., and Panek, M. (2020). Biological Therapies of Severe Asthma and Their Possible Effects on Airway Remodeling. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01134"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"A4636","DOI":"10.1016\/j.chest.2024.06.2809","article-title":"Long-term safety of biologics in asthma: A systematic literature review","volume":"166","author":"Benson","year":"2024","journal-title":"Chest"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.jaip.2020.10.010","article-title":"Long-term therapy response to anti\u2013IL-5 biologics in severe asthma\u2014A real-life evaluation","volume":"9","author":"Eger","year":"2021","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.resinv.2025.03.007","article-title":"Long-term, real-world effectiveness of biologics for severe uncontrolled asthma: The PROSPECT study","volume":"63","author":"Asai","year":"2025","journal-title":"Respir. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.chest.2023.10.046","article-title":"Clinical response and remission in patients with severe asthma treated with biologic therapies","volume":"165","author":"Hansen","year":"2024","journal-title":"Chest"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2317356","DOI":"10.1080\/07853890.2024.2317356","article-title":"Clinical characteristics of complete responders versus non-complete responders to omalizumab, benralizumab and mepolizumab in patients with severe asthma: A long-term retrospective analysis","volume":"56","author":"Navarro","year":"2024","journal-title":"Ann. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.1111\/all.16178","article-title":"Real-world biologics response and super-response in the International Severe Asthma Registry cohort","volume":"79","author":"Denton","year":"2024","journal-title":"Allergy"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"112189","DOI":"10.1016\/j.intimp.2024.112189","article-title":"Precision Medicine for Severe Asthma\u2014Biological Targeted Therapy","volume":"134","author":"Sun","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s41030-019-00109-1","article-title":"Severe Asthma and Biological Therapy: When, Which, and for Whom","volume":"6","author":"Rogliani","year":"2020","journal-title":"Pulm. Ther."},{"key":"ref_21","first-page":"250023","article-title":"Biologic Treatment Discontinuation in Severe Asthma: A Real-Life Study on Factors Influencing Clinical Remission and Physician Decision-Making","volume":"46","author":"Onalan","year":"2025","journal-title":"Ann. Allergy Asthma Immunol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/6\/2444\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T10:14:51Z","timestamp":1774260891000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/6\/2444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,23]]},"references-count":21,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["jcm15062444"],"URL":"https:\/\/doi.org\/10.3390\/jcm15062444","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,23]]}}}