Published April 22, 2026
| Version v1
Journal article
Open
Clinical outcomes in severe asthma patients switching biologic therapies: A real-world cohort analysis
Authors/Creators
- 1. Department of Allergology, Medical University of Sofia, University Hospital Alexandrovska, Sofia, Bulgaria
- 2. Department of Organization and Economics of the Pharmaceutical System, Medical University of Sofia, Faculty of Pharmacy, Sofia, Bulgaria
- 3. Department of Pharmaceutical Sciences and Social Pharmacy, Faculty of Pharmacy, Medical University Pleven, Pleven, Bulgaria
Description
Background: Severe asthma is a heterogeneous condition in which biologic therapies targeting type 2 inflammation have substantially improved disease control. However, a proportion of patients fail to achieve a sustained response, necessitating biologic switching in routine clinical practice.
Objective: Evaluate real-world patterns, clinical outcomes, and determinants of biologic switching in patients with severe asthma.
Methods: This 15-year ambispective cohort study evaluated patients with severe asthma treated with biologic therapies between 2009 and 2025. Patients were classified as never-switchers or switchers. Clinical outcomes, exacerbation burden, oral corticosteroid use, lung function, and inflammatory biomarkers were assessed at baseline, 4/6 months, and 12 months. Comparative analyses were performed across cohorts.
Results: Among 345 included patients, 116 (33.6%) underwent biologic switching. Inadequate clinical efficacy was the predominant reason for switching, frequently accompanied by persistent upper-airway comorbidities. Clinical improvement was observed following both initial biologic initiation and subsequent switching; however, patients requiring switching exhibited a higher residual disease burden and rarely achieved the level of disease control observed in stable patients. Early response at 4/6 months was informative for longer-term outcomes, and switching was safe.
Conclusion: In real-world practice, biologic switching represents a common and clinically meaningful strategy in severe asthma. Early treatment response may assist in identifying patients requiring timely reassessment and individualized therapeutic optimization.
Files
PHAR_article_188786.pdf
Files
(609.2 kB)
| Name | Size | Download all |
|---|---|---|
|
md5:4de57ff18b8b5da8f1d269e3deb2fc32
|
476.6 kB | Preview Download |
|
md5:c63cc2dc6c935e3196347811fae72d47
|
132.6 kB | Preview Download |
Additional details
References
- Al Awn L, AlAmmari M, AlAbdulkarim D, AlAhmed R, Yadav B, AL-Jahdali H (2025) Evaluating safety and effectiveness of switching biologics in managing severe asthma patients. Journal of Asthma and Allergy Volume 18: 1161–1166. https://doi.org/10.2147/JAA.S516225
- Al-Ahmad M, Ali A, Maher A (2023) Omalizumab transitions in severe asthma: Factors influencing switching decisions and timing for optimal response. Medical Principles and Practice 32: 323–331. https://doi.org/10.1159/000534319
- Bagnasco D, Passalacqua G, Caminati M, Heffler E, Menzella F, De Ferrari L, Riccio AM, Folli C, Canonica GW (2020) Evolving phenotypes to endotypes: Is precision medicine achievable in asthma? Expert Review of Respiratory Medicine 14: 163–172. https://doi.org/10.1080/17476348.2020.1703675
- Bourdin A, Brusselle G, Couillard S, Fajt ML, Heaney LG, Israel E, McDowell PJ, Menzies-Gow A, Martin N, Mitchell PD, Petousi N, Quirce S, Schleich F, Pavord ID (2024) Phenotyping of severe asthma in the era of broad-acting anti-asthma biologics. The Journal of Allergy and Clinical Immunology: In Practice 12: 809–823. https://doi.org/10.1016/j.jaip.2024.01.023
- Busse WW (2025) The role of biologics in inducing remission in asthma. Annals of Allergy, Asthma & Immunology 134: 19–30. https://doi.org/10.1016/j.anai.2024.09.021
- Caminati M, Marcon A, Guarnieri G, Miotti J, Bagnasco D, Carpagnano GE, Pelaia G, Vaia R, Maule M, Vianello A, Senna G (2023) Benralizumab efficacy in late non-responders to mepolizumab and variables associated with occurrence of switching: A real-word perspective. Journal of Clinical Medicine 12: 1836. https://doi.org/10.3390/jcm12051836
- Canonica GW, Virchow JC, Bourdin A, Jacob-Nara J, Borsos K, Stanford RH, Wang Z, Soliman M, Huynh L, Haque F, Duh MS, Cheng W-H (2025) Real-world comparative effectiveness of biologic therapies in severe asthma: EU-ADVANTAGE. ERJ Open Research 11: 01217–02024. https://doi.org/10.1183/23120541.01217-2024
- Canonica GW, Blasi F, Carpagnano GE, Guida G, Heffler E, Paggiaro P, Allegrini C, Antonelli A, Aruanno A, Bacci E, Bagnasco D, Beghè B, Bonavia M, Bonini M, Brussino L, Caiaffa MF, Calabrese C, Camiciottoli G, Caminati M, Caruso C, Cavallini M, Chieco Bianchi F, Conte ME, Corsico AG, Cosmi L, Costantino M, Costanzo G, Crivellaro M, D'Alò S, D'Amato M, Detoraki A, Di Proietto MC, Facciolongo NC, Ferri S, Fierro V, Foschino MP, Latorre M, Lombardi C, Macchia L, Milanese M, Montagni M, Parazzini EM, Parente R, Passalacqua G, Patella V, Pelaia G, Pini L, Puggioni F, Ricciardi L, Ridolo E, Rolo J, Scichilone N, Scioscia G, Senna G, Solidoro P, Varricchi G, Vianello A, Yacoub MR, Yang B (2023) Severe asthma network italy definition of clinical remission in severe asthma: A Delphi consensus. Journal of Allergy and Clinical Immunology: In Practice 11: 3629–3637. https://doi.org/10.1016/j.jaip.2023.07.041
- Carpagnano GE, Pelaia C, D'Amato M, Crimi N, Scichilone N, Scioscia G, Resta O, Calabrese C, Pelaia G, Quarato CMI, Foschino Barbaro MP (2020) Switching from omalizumab to mepolizumab: real-life experience from Southern Italy. Therapeutic Advances in Respiratory Disease 14: 1753466620929231. https://doi.org/10.1177/1753466620929231
- Caruso C, Cameli P, Altieri E, Aliani M, Bracciale P, Brussino L, Caiaffa MF, Canonica GW, Centanni S, D'Amato M, Del Giacco S, De Michele F, Pastorello EA, Pelaia G, Rogliani P, Romagnoli M, Schino P, Caminati M, Vultaggio A, Zullo A, Rizzoli S, Boarino S, Vitiello G, Menzella F, Di Marco F (2022) Switching from one biologic to benralizumab in patients with severe eosinophilic asthma: An ANANKE study post hoc analysis. Frontiers in Medicine 9: 950883. https://doi.org/10.3389/fmed.2022.950883
- Couillard S, Jackson DJ, Pavord ID, Wechsler ME (2025) Choosing the right biologic for the right patient with severe asthma. Chest 167: 330–342. https://doi.org/10.1016/j.chest.2024.08.045
- Crimi C, Nolasco S, Noto A, Maglio A, Quaranta VN, Di Bona D, Scioscia G, Papia F, Caiaffa MF, Calabrese C, D'Amato M, Pelaia C, Campisi R, Vitale C, Ciampo L, Dragonieri S, Minenna E, Massaro F, Gallotti L, Macchia L, Triggiani M, Scichilone N, Valenti G, Pelaia G, Foschino Barbaro MP, Carpagnano GE, Vatrella A, Crimi N, Intravaia R, Porto M, Impellizzeri P, Frazzetto V, Bonsignore M, Giannì C, Nardo AA, Vignera F, Busceti MT, Lombardo N, Lacedonia D, Tondo P, Soccio P, Quarato CMI, Montagnolo F, Salerno V, Maselli L, Julai E, Coppa F, Grimaldi L, Julai E, Carrieri I, Sola A, Balestrino M, Mariniello DF, Carrieri I, Benfante A, Spadaro G, Detoraki A, Ricciardi L, Antonio F, Valeria L (2024) Long-term clinical and sustained REMIssion in severe eosinophilic asthma treated with Mepolizumab: The REMI-M study. The Journal of Allergy and Clinical Immunology: In Practice 12: 3315–3327. https://doi.org/10.1016/j.jaip.2024.08.033
- Crossingham I, Richardson R, Hinks TS, Spencer S, Couillard S, Maynard-Paquette A-C, Thomassen D, Howell I (2022) Biologics for chronic severe asthma: a network meta-analysis. Cochrane Database of Systematic Reviews 10: CD015411. https://doi.org/10.1002/14651858.CD015411
- Dragonieri S, Portacci A, Quaranta VN, Carpagnano GE (2024) Advancing care in severe asthma: The art of switching biologics. Advances in Respiratory Medicine 92: 110–122. https://doi.org/10.3390/arm92020014
- Drick N, Milger K, Seeliger B, Fuge J, Korn S, Buhl R, Schuhmann M, Herth F, Kendziora B, Behr J, Kneidinger N, Bergmann K-C, Taube C, Welte T, Suhling H (2020) Switch from IL-5 to IL-5-receptor α antibody treatment in severe eosinophilic asthma. Journal of Asthma and Allergy Volume 13: 605–614. https://doi.org/10.2147/JAA.S270298
- Faria N, Costa MI, Fernandes AL, Fernandes A, Fernandes B, Machado DC, Machado F, Simão L, Ribeiro L, Ferreira L, Boaventura R, Lima R, Ferreira J (2025) Biologic therapies for severe asthma: Current insights and future directions. Journal of Clinical Medicine 14. https://doi.org/10.3390/jcm14093153
- Frix A-N, Heaney LG, Dahlén B, Mihaltan F, Sergejeva S, Popović-Grle S, Sedlak V, Lehtimäki L, Bourdin A, Korn S, Zervas E, Csoma Z, Lúðvíksdóttir D, Butler M, Canonica GW, Grisle I, Bieksiene K, Ten Brinke A, Kuna P, Chaves Loureiro C, Nenasheva NM, Lazic Z, Škrgat S, Ramos-Barbon D, Leuppi J, Gemicioglu B, Bossios A, Porsbjerg CM, Bel EH, Djukanovic R, Louis R (2022) Heterogeneity in the use of biologics for severe asthma in Europe: a SHARP ERS study. ERJ Open Research 8: 00273–02022. https://doi.org/10.1183/23120541.00273-2022
- Hansen S, Baastrup Søndergaard M, Von Bülow A, Bjerrum A-S, Schmid J, Rasmussen LM, Johnsen CR, Ingebrigtsen T, Håkansson KEJ, Johansson SL, Bisgaard M, Assing KD, Hilberg O, Ulrik C, Porsbjerg C (2024) Clinical response and remission in patients with severe asthma treated with biologic therapies. CHEST 165: 253–266. https://doi.org/10.1016/j.chest.2023.10.046
- Kavanagh JE, Hearn AP, d'Ancona G, Dhariwal J, Roxas C, Green L, Thomson L, Fernandes M, Kent BD, Nanzer AM, Jackson DJ (2021) Benralizumab after sub‐optimal response to mepolizumab in severe eosinophilic asthma. Allergy 76: 1890–1893. https://doi.org/10.1111/all.14693
- Khateeb J, Kramer MR, Freund O, Mhameed R, Naamany E, Kupershmidt A, Elkayam G, Breslavsky A, Rosengarten D, Dotan Y, Wand O, Bar-Shai A (2025) Real-world evidence of tezepelumab for severe asthma: a retrospective multicentre cohort. ERJ Open Research 11: 00314–02025. https://doi.org/10.1183/23120541.00314-2025
- Kuks PJM, Karp T, Hartman JE, Kraft M, Siddiqui S, Fabbri LM, Beghé B, Rabe KF, Papi A, Brightling CE, Singh D, Li X, Kocks JWH, Scaffidi-Argentina U, Kerstjens HAM, Heijink IH, Pouwels SD, Slebos D, Van Den Berge M (2025) Cluster Analysis to Identify Distinct Asthma Phenotypes in the ATLANTIS Cohort. Allergy: Advance online publication. https://doi.org/10.1111/all.70127
- Lafarge L, Pilette C, Bugli C, Froidure A (2024) Effectiveness of biologic switching in a real‐life, Belgian severe asthma cohort. Immunity, Inflammation and Disease 12: e70023. https://doi.org/10.1002/iid3.70023
- Lipworth BJ, Greig R, Chan R, Kuo CR, Jackson C (2025) Head-to-head comparison of biologic efficacy in asthma: What have we learned? Allergy 80: 1226–1241. https://doi.org/10.1111/all.16537
- Liu MC, Chipps B, Munoz X, Devouassoux G, Bergna M, Smith SG, Price RG, Galkin DV, Azmi J, Mouneimne D, Albers FC, Chapman KR (2021) Benefit of switching to mepolizumab from omalizumab in severe eosinophilic asthma based on patient characteristics. Respiratory Research 22: 144. https://doi.org/10.1186/s12931-021-01733-9
- Matsumoto S, Kamide Y, Fujino N, Yamada M, Ono Y, Kobayashi S, Sato T, Sekiya K, Endo T, Tamada T, Ichikawa T, Aizawa H, Sano H, Kyogoku Y, Saito T, Konno S, Suzuki M, Okutomo K, Taniguchi M, Sugiura H (2025) A real-world clustering analysis reveals heterogeneous response patterns to biologic therapy in severe asthma. Exploration of Asthma & Allergy 3: 100990. https://doi.org/10.37349/eaa.2025.100990
- Matsumoto-Sasaki M, Simizu K, Suzuki M, Suzuki M, Kimura H, Nakamaru Y, Ito YM, Homma A, Konno S (2022) Clinical characteristics of patients and factors associated with switching biologics in asthma. Journal of Asthma and Allergy Volume 15: 187–195. https://doi.org/10.2147/JAA.S348513
- Menzies-Gow A, Hoyte FL, Price DB, Cohen D, Barker P, Kreindler J, Jison M, Brooks CL, Papeleu P, Katial R (2022a) Clinical remission in severe asthma: A pooled post hoc analysis of the patient journey with Benralizumab. Advances in Therapy 39: 2065–2084. https://doi.org/10.1007/s12325-022-02098-1
- Menzies-Gow A, Bafadhel M, Busse WW, Casale TB, Kocks JWH, Pavord ID, Szefler SJ, Woodruff PG, de Giorgio-Miller A, Trudo F, Fageras M, Ambrose CS (2020) An expert consensus framework for asthma remission as a treatment goal. Journal of Allergy and Clinical Immunology 145: 757–765. https://doi.org/10.1016/j.jaci.2019.12.006
- Menzies-Gow AN, McBrien C, Unni B, Porsbjerg CM, Al-Ahmad M, Ambrose CS, Dahl Assing K, Von Bülow A, Busby J, Cosio BG, FitzGerald JM, Garcia Gil E, Hansen S, Heaney LG, Hew M, Jackson DJ, Kallieri M, Loukides S, Lugogo NL, Papaioannou AI, Larenas-Linnemann D, Moore WC, Perez-de-Llano LA, Rasmussen LM, Schmid JM, Siddiqui S, Alacqua M, Tran TN, Suppli Ulrik C, Upham JW, Wang E, Bulathsinhala L, Carter VA, Chaudhry I, Eleangovan N, Murray RB, Price CA, Price DB (2022b) Real world biologic use and switch patterns in severe asthma: Data from the international severe asthma registry and the US CHRONICLE Study. Journal of Asthma and Allergy Volume 15: 63–78. https://doi.org/10.2147/JAA.S328653
- Mobayed H, Al-Nesf M, Ibrahim T, Aqel S, Al-Ahmad M, Bousquet J (2025) Secondary non-response to biologic treatment in patients with severe asthma. Journal of Asthma and Allergy Volume 18: 795–800. https://doi.org/10.2147/JAA.S517784
- Naumova VV, Beltyukov EK, Kiseleva DV, Bykova GA, Smolenskaya OG, Shtanova AA, Stepina DА (2023) Targeted therapy for severe asthma: switching biological agents in real clinical practice — causes and consequences. Russian Journal of Allergy 20: 439–454. https://doi.org/10.36691/RJA15993
- Numata T, Araya J, Miyagawa H, Okuda K, Fujita Y, Utsumi H, Takekoshi D, Hashimoto M, Minagawa S, Ishikawa T, Hara H, Kuwano K (2021) Effectiveness of switching biologics for severe asthma patients in Japan: A single-center retrospective study. Journal of Asthma and Allergy Volume 14: 609–618. https://doi.org/10.2147/JAA.S311975
- Okwuofu EO, Yong ACH, Lim JCW, Stanslas J (2025) The era of multiple biologics: Is combination and switching an option in the management of severe asthma? Pulmonary Pharmacology & Therapeutics 90: 102375. https://doi.org/10.1016/j.pupt.2025.102375
- Papaioannou AI, Fouka E, Papakosta D, Papiris S, Loukides S (2021) Switching between biologics in severe asthma patients. When the first choice is not proven to be the best. Clinical & Experimental Allergy 51: 221–227. https://doi.org/10.1111/cea.13809
- Pavord I, Katial RK, Jackson DJ, Rogers L, Lega Hoyte FC, Smolen J, Wechsler ME, Akuthota P, Jackson DJ (2025) Current data on biologics: Evaluating clinical remission in asthma. Journal of Allergy and Clinical Immunology 156: S15–S19. https://doi.org/10.1016/j.jaci.2025.05.034
- Pelaia C, Crimi C, Nolasco S, Carpagnano GE, Brancaccio R, Buonamico E, Campisi R, Gagliani C, Patella V, Pelaia G, Valenti G, Crimi N (2021) Switch from Omalizumab to Benralizumab in allergic patients with severe eosinophilic asthma: A real-life experience from Southern Italy. Biomedicines 9: 1822. https://doi.org/10.3390/biomedicines9121822
- Porsbjerg C, Rupani H, Brannan JD, Ueki S, Nawijn MC, Erjefält JS, Chanez P, Anderson GP, Pavord ID (2025) Reframing remission in severe asthma: a conceptual framework for distinguishing disease activity versus damage. The Lancet Respiratory Medicine 13: 1026–1040. https://doi.org/10.1016/S2213-2600(25)00299-1
- Scelo G, Tran TN, Le TT, Fagerås M, Dorscheid D, Busby J, Al-Ahmad M, Al-Lehebi R, Altraja A, Beastall A, Bergeron C, Bjermer L, Bjerrum AS, Cano-Rosales DJ, Canonica GW, Carter V, Charriot J, Christoff GC, Cosio BG, Denton E, Fernandez-Sanchez MJ, Fonseca JA, Gibson PG, Goh C, Heaney LG, Heffler E, Hew M, Iwanaga T, Katial R, Koh MS, Kuna P, Larenas-Linnemann D, Lehtimäki L, Mahboub B, Martin N, Matsumoto H, Menzies-Gow AN, Papadopoulos NG, Patel P, Perez-De-Llano L, Peters M, Pfeffer PE, Popov TA, Porsbjerg CM, Rhee CK, Sadatsafavi M, Taillé C, Torres-Duque CA, Tsai M-J, Ulrik CS, Upham JW, Von Bülow A, Wang E, Wechsler ME, Price DB (2024) Exploring definitions and predictors of response to biologics for severe asthma. The Journal of Allergy and Clinical Immunology: In Practice 12: 2347–2361. https://doi.org/10.1016/j.jaip.2024.05.016
- Scioscia G, Nolasco S, Campisi R, Quarato CMI, Caruso C, Pelaia C, Portacci A, Crimi C (2023) Switching biological therapies in severe asthma. International Journal of Molecular Sciences 24. https://doi.org/10.3390/ijms24119563
- Solidoro P, Nicola S, Ridolfi I, Canonica GW, Blasi F, Paggiaro P, Heffler E, Bagnasco D, Patrucco F, Ribolla F, Bucca C, Rolla G, Albera C, Brussino L (2022) Biologics in severe eosinophilic asthma: Three-year follow-up in a SANI single center. Biomedicines 10: 200. https://doi.org/10.3390/biomedicines10020200
- Sumi T, Ishigooka T, Matsuura K, Ikeda T, Koshino Y, Suzuki K, Yamada Y, Chiba H (2025) Switching to tezepelumab from other biologics in patients with severe asthma: a retrospective study. Respiratory Investigation 63: 592–599. https://doi.org/10.1016/j.resinv.2025.04.022
- Tran T, Chen S, Emmanuel B, Altraja A, Bourdin A, Sheu C-C, Tsai M-J, Hoyte F, Quinton A, Cook B, Bulathsinhala L, Henley W, Goh CYY, Liu Y, Ariti C, Carter V, Price D (2025) Real-world biologic use patterns in severe asthma, 2015–2021: The CLEAR Study. Pragmatic and Observational Research Volume 16: 51–66. https://doi.org/10.2147/POR.S497033
- Upham JW, Le Lievre C, Jackson DJ, Masoli M, Wechsler ME, Price DB, Mansur A, Detoraki A, Altraja A, James A, Nanzer-Kelly A, Côté A, Menzies-Gow A, Papaioannou A, Cheffins A-M, Bourdin A, Mahboub B, Lipworth B, Celis-Preciado CA, Torres-Duque C, Bucca C, Porsbjerg C, Ulrik C, Corrigan C, Taube C, Farah C, Katelaris C, Langton D, Ryan D, Larenas-Linnemann D, Zervas E, Heffler E, Hoyte F, Puggioni F, Christoff G, Canonica GW, Carpagnano GE, Guida G, Katsoulotos G, Brusselle G, Rupani H, Jersmann H, Clifton I, Dhariwal J, Fingleton J, Duke J, Rimmer J, Douglass J, Fonseca J, Van Boven J, Corless J, Harrington J, Maspero J, Miguel JL, Pipatvech K, Kenny K, Chapman K, Kostikas K, Lehtimäki L, Chung LP, Heaney L, Hang L-W, Boulet L-P, Perez-de-Llano L, Ricciardi L, Idrees M, Milanese M, Conte ME, Costantino MT, Siyue MK, Fitzgerald M, Hew M, Peters M, Tsai M-J, Patel M, Khan MH, Sadatsafavi M, Al-Ahmad M, Yacoub M-R, De Gennaro M, Radhakrishna N, Hanania NA, Papadopoulos N, Lugogo N, Linaker N, Crimi N, Dennison P, Nair P, Mitchell PD, O'Byrne P, Pfeffer P, Kauppi P, Hughes P, Middleton P, Wark P, Bardin P, Fu P-K, Akuthota P, Chaudhuri R, Campos R, Al-Lehebi R, Parente R, Francisco R, Wenzel S, Pierachille S, Pawar S, Loukides S, Fowler S, Mackenzie T, Brown T, Lee Tan T, Björnsdóttir U, McDonald V, Lawriwskyj V, Backer V, Vasileva V, Chien Y-C, Harrington Z (2021) Defining a severe asthma super-responder: Findings from a Delphi process. The Journal of Allergy and Clinical Immunology: In Practice 9: 3997–4004. https://doi.org/10.1016/j.jaip.2021.06.041