Switching Biological Therapies in Severe Asthma
Abstract
:1. Introduction
1.1. Omalizumab
1.1.1. Clinical Trials
1.1.2. Real-Life Studies
1.2. Mepolizumab
1.2.1. Clinical Trials
1.2.2. Real-Life Studies
1.3. Benralizumab
1.3.1. Clinical Trials
1.3.2. Real-Life Studies
1.4. Dupilumab
1.4.1. Clinical Trials
1.4.2. Real-Life Studies
2. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Porsbjerg, C.; Melén, E.; Lehtimäki, L.; Shaw, D. Asthma. Lancet 2023, 401, 858–873. [Google Scholar] [CrossRef] [PubMed]
- Hekking, P.P.W.; Wener, R.R.; Amelink, M.; Zwinderman, A.H.; Bouvy, M.L.; Bel, E.H. The prevalence of severe refractory asthma. J. Allergy Clin. Immunol. 2015, 135, 896–902. [Google Scholar] [CrossRef] [PubMed]
- Lefebvre, P.; Duh, M.S.; Lafeuille, M.H.; Gozalo, L.; Desai, U.; Robitaille, M.N.; Albers, F.; Yancey, S.; Ortega, H.; Forshag, M.; et al. Acute and chronic systemic corticosteroid-related complications in patients with severe asthma. J. Allergy Clin. Immunol. 2015, 136, 1488–1495. [Google Scholar] [CrossRef] [PubMed]
- Fahy, J.V. Type 2 inflammation in asthma—Present in most, absent in many. Nat. Rev. Immunol. 2014, 15, 57–65. [Google Scholar] [CrossRef]
- Doroudchi, A.; Pathria, M.; Modena, B.D. Asthma biologics: Comparing trial designs, patient cohorts and study results. Ann. Allergy Asthma Immunol. 2020, 124, 44–56. [Google Scholar] [CrossRef]
- McGregor, M.C.; Krings, J.G.; Nair, P.; Castro, M. Role of biologics in asthma. Am. J. Respir. Crit. Care Med. 2019, 199, 433–445. [Google Scholar] [CrossRef]
- Pelaia, C.; Pelaia, G.; Longhini, F.; Crimi, C.; Calabrese, C.; Gallelli, L.; Sciacqua, A.; Vatrella, A. Monoclonal Antibodies Targeting Alarmins: A New Perspective for Biological Therapies of Severe Asthma. Biomedicines 2021, 9, 1108. [Google Scholar] [CrossRef]
- Nolasco, S.; Pelaia, C.; Scioscia, G.; Campisi, R.; Crimi, C. Tezepelumab for asthma. Drugs Today 2022, 58, 591–603. [Google Scholar] [CrossRef]
- Pelaia, C.; Pelaia, G.; Crimi, C.; Maglio, A.; Gallelli, L.; Terracciano, R.; Vatrella, A. Tezepelumab: A Potential New Biological Therapy for Severe Refractory Asthma. Int. J. Mol. Sci. 2021, 22, 4369. [Google Scholar] [CrossRef]
- Salter, B.; Lacy, P.; Mukherjee, M. Biologics in Asthma: A Molecular Perspective to Precision Medicine. Front. Pharmacol. 2022, 12, 3867. [Google Scholar] [CrossRef]
- Global Initiative for Asthma (GINA). GINA Report, Global Strategy for Asthma Management and Prevention. 2022. Available online: https://ginasthma.org (accessed on 5 March 2023).
- Oishi, K.; Hamada, K.; Murata, Y.; Matsuda, K.; Ohata, S.; Yamaji, Y.; Asami-Noyama, M.; Edakuni, N.; Kakugawa, T.; Hirano, T.; et al. A Real-World Study of Achievement Rate and Predictive Factors of Clinical and Deep Remission to Biologics in Patients with Severe Asthma. J. Clin. Med. 2023, 12, 2900. [Google Scholar] [CrossRef]
- Politis, J.; Bardin, P.G. Switching Biological Therapies in Adults with Severe Asthma: What Are the Dilemmas and Is It Worthwhile? Ann. Am. Thorac. Soc. 2022, 19, 1965–1970. [Google Scholar] [CrossRef]
- Loureiro, C.C.; Amaral, L.; Ferreira, J.A.; Lima, R.; Pardal, C.; Fernandes, I.; Semedo, L.; Arrobas, A. Omalizumab for Severe Asthma: Beyond Allergic Asthma. BioMed Res. Int. 2018, 2018, 3254094. [Google Scholar] [CrossRef]
- Rubini, N.P.M.; Ensina, L.F.C.; Silva, E.M.K.; Sano, F.; Solé, D. Effectiveness and safety of Omalizumab in the treatment of chronic spontaneous urticaria: Systematic review and meta-analysis. Allergol. Immunopathol. 2019, 47, 515–522. [Google Scholar] [CrossRef]
- Gevaert, P.; Omachi, T.A.; Corren, J.; Mullol, J.; Han, J.; Lee, S.E.; Kaufman, D.; Ligueros-Saylan, M.; Howard, M.; Zhu, R.; et al. Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials. J. Allergy Clin. Immunol. 2020, 146, 595–605. [Google Scholar] [CrossRef]
- Humbert, M.; Beasley, R.; Ayres, J.; Slavin, R.; Hébert, J.; Bousquet, J.; Beeh, K.M.; Ramos, S.; Canonica, G.W.; Hedgecock, S.; et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy 2005, 60, 309–316. [Google Scholar] [CrossRef]
- Busse, W.; Corren, J.; Lanier, B.Q.; McAlary, M.; Fowler-Taylor, A.; Della Cioppa, G.; van As, A.; Gupta, N. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J. Allergy Clin. Immunol. 2001, 108, 184–190. [Google Scholar] [CrossRef]
- Holgate, S.T.; Chuchalin, A.G.; Hébert, J.; Lötvall, J.; Persson, G.B.; Chung, K.F.; Bousquet, J.; Kerstjens, H.A.; Fox, H.; Thirlwell, J.; et al. Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma. Clin. Exp. Allergy 2004, 34, 632–638. [Google Scholar] [CrossRef]
- Solèr, M.; Matz, J.; Townley, R.; Buhl, R.; O’Brien, J.; Fox, H.; Thirlwell, J.; Gupta, N.; Della Cioppa, G. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur. Respir. J. 2001, 18, 254–261. [Google Scholar] [CrossRef]
- Hanania, N.A.; Wenzel, S.; Roseń, K.; Hsieh, H.J.; Mosesova, S.; Choy, D.F.; Lal, P.; Arron, J.R.; Harris, J.M.; Busse, W. Exploring the effects of omalizumab in allergic asthma: An analysis of biomarkers in the EXTRA study. Am. J. Respir. Crit. Care Med. 2013, 187, 804–811. [Google Scholar] [CrossRef]
- Bousquet, J.; Rabe, K.; Humbert, M.; Chung, K.F.; Berger, W.; Fox, H.; Ayre, G.; Chen, H.; Thomas, K.; Blogg, M.; et al. Predicting and evaluating response to omalizumab in patients with severe allergic asthma. Respir. Med. 2007, 101, 1483–1492. [Google Scholar] [CrossRef] [PubMed]
- Massanari, M.; Holgate, S.T.; Busse, W.W.; Jimenez, P.; Kianifard, F.; Zeldin, R. Effect of omalizumab on peripheral blood eosinophilia in allergic asthma. Respir. Med. 2010, 104, 188–196. [Google Scholar] [CrossRef] [PubMed]
- Chapman, K.R.; Albers, F.C.; Chipps, B.; Muñoz, X.; Devouassoux, G.; Bergna, M.; Galkin, D.; Azmi, J.; Mouneimne, D.; Price, R.G.; et al. The clinical benefit of mepolizumab replacing omalizumab in uncontrolled severe eosinophilic asthma. Allergy 2019, 74, 1716–1726. [Google Scholar] [CrossRef] [PubMed]
- Juniper, E.F.; Svensson, K.; Mörk, A.C.; Ståhl, E. Measurement properties and interpretation of three shortened versions of the asthma control questionnaire. Respir. Med. 2005, 99, 553–558. [Google Scholar] [CrossRef] [PubMed]
- Ortega, H.G.; Liu, M.C.; Pavord, I.D.; Brusselle, G.G.; FitzGerald, J.M.; Chetta, A.; Humbert, M.; Katz, L.E.; Keene, O.N.; Yancey, S.W.; et al. Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma. N. Engl. J. Med. 2014, 371, 1198–1207. [Google Scholar] [CrossRef] [PubMed]
- Pavord, I.D.; Korn, S.; Howarth, P.; Bleecker, E.R.; Buhl, R.; Keene, O.N.; Ortega, H.; Chanez, P. Mepolizumab for severe eosinophilic asthma (DREAM): A multicentre, double-blind, placebo-controlled trial. Lancet 2012, 380, 651–659. [Google Scholar] [CrossRef]
- Chupp, G.L.; Bradford, E.S.; Albers, F.C.; Bratton, D.J.; Wang-Jairaj, J.; Nelsen, L.M.; Trevor, J.L.; Magnan, A.; ten Brinke, A. Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): A randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial. Lancet Respir. Med. 2017, 5, 390–400. [Google Scholar] [CrossRef]
- Liu, M.C.; Chipps, B.; Munoz, X.; Devouassoux, G.; Bergna, M.; Smith, S.G.; Price, R.G.; Galkin, D.V.; Azmi, J.; Mouneimne, D.; et al. Benefit of switching to mepolizumab from omalizumab in severe eosinophilic asthma based on patient characteristics. Respir. Res. 2021, 22, 144. [Google Scholar] [CrossRef]
- Magnan, A.; Bourdin, A.; Prazma, C.M.; Albers, F.C.; Price, R.G.; Yancey, S.W.; Ortega, H. Treatment response with mepolizumab in severe eosinophilic asthma patients with previous omalizumab treatment. Allergy 2016, 71, 1335–1344. [Google Scholar] [CrossRef]
- Abraham, I.; Alhossan, A.; Lee, C.S.; Kutbi, H.; MacDonald, K. ‘Real-life’ effectiveness studies of omalizumab in adult patients with severe allergic asthma: Systematic review. Allergy 2016, 71, 593–610. [Google Scholar] [CrossRef]
- Menzella, F.; Fontana, M.; Contoli, M.; Ruggiero, P.; Galeone, C.; Capobelli, S.; Simonazzi, A.; Catellani, C.; Scelfo, C.; Castagnetti, C.; et al. Efficacy and Safety of Omalizumab Treatment Over a 16-Year Follow-Up: When a Clinical Trial Meets Real-Life. J. Asthma Allergy 2022, 15, 505. [Google Scholar] [CrossRef]
- Bousquet, J.; Humbert, M.; Gibson, P.G.; Kostikas, K.; Jaumont, X.; Pfister, P.; Nissen, F. Real-World Effectiveness of Omalizumab in Severe Allergic Asthma: A Meta-Analysis of Observational Studies. J. Allergy Clin. Immunol. Pract. 2021, 9, 2702–2714. [Google Scholar] [CrossRef]
- Menzies-Gow, A.N.; McBrien, C.; Unni, B.; Porsbjerg, C.M.; Al-Ahmad, M.; Ambrose, C.S.; Dahl Assing, K.; von Bülow, A.; Busby, J.; Cosio, B.G.; et al. Real World Biologic Use and Switch Patterns in Severe Asthma: Data from the International Severe Asthma Registry and the US Chronicle Study. J. Asthma Allergy 2022, 15, 63. [Google Scholar] [CrossRef]
- Bagnasco, D.; Menzella, F.; Caminati, M.; Caruso, C.; Guida, G.; Bonavia, M.; Riccio, A.; Milanese, M.; Manfredi, A.; Senna, G.; et al. Efficacy of mepolizumab in patients with previous omalizumab treatment failure: Real-life observation. Allergy 2019, 74, 2539–2541. [Google Scholar] [CrossRef]
- Carpagnano, G.E.; Pelaia, C.; D’Amato, M.; Crimi, N.; Scichilone, N.; Scioscia, G.; Resta, O.; Calabrese, C.; Pelaia, G.; Quarato, C.M.I.; et al. Switching from omalizumab to mepolizumab: Real-life experience from Southern Italy. Ther. Adv. Respir. Dis. 2020, 14, 175346662092923. [Google Scholar] [CrossRef]
- Carpagnano, G.E.; Resta, E.; Povero, M.; Pelaia, C.; D’Amato, M.; Crimi, N.; Scichilone, N.; Scioscia, G.; Resta, O.; Calabrese, C.; et al. Clinical and economic consequences of switching from omalizumab to mepolizumab in uncontrolled severe eosinophilic asthma. Sci. Rep. 2021, 11, 5453. [Google Scholar] [CrossRef]
- Pelaia, C.; Crimi, C.; Nolasco, S.; Carpagnano, G.E.; Brancaccio, R.; Buonamico, E.; Campisi, R.; Gagliani, C.; Patella, V.; Pelaia, G.; et al. Switch from Omalizumab to Benralizumab in Allergic Patients with Severe Eosinophilic Asthma: A Real-Life Experience from Southern Italy. Biomedicines 2021, 9, 1822. [Google Scholar] [CrossRef]
- O’reilly, E.; Casey, D.; Ibrahim, H.; McGrath, A.; McHugh, T.; Vairamani, P.; Murphy, J.; Plant, B.; Murphy, D.M. Real-World Clinical Outcomes in Asthmatic Patients Switched from Omalizumab to Anti-Interleukin-5 Therapy. J. Asthma Allergy 2022, 15, 935–937. [Google Scholar] [CrossRef]
- Pelaia, C.; Vatrella, A.; Busceti, M.T.; Gallelli, L.; Terracciano, R.; Savino, R.; Pelaia, G. Severe eosinophilic asthma: From the pathogenic role of interleukin-5 to the therapeutic action of mepolizumab. Drug Des. Devel. Ther. 2017, 11, 3137. [Google Scholar] [CrossRef]
- Leckie, M.J.; Ten Brinke, A.; Khan, J.; Diamant, Z.; O’xonnor, B.J.; Walls, C.M.; Mathur, A.K.; Cowley, H.C.; Chung, K.F.; Djukanovic, R.; et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000, 356, 2144–2148. [Google Scholar] [CrossRef]
- Flood-Page, P.; Swenson, C.; Faiferman, I.; Matthews, J.; Williams, M.; Brannick, L.; Robinson, D.; Wenzel, S.; Busse, W.; Hansel, T.T.; et al. A Study to Evaluate Safety and Efficacy of Mepolizumab in Patients with Moderate Persistent Asthma. Am. J. Respir. Crit. Care Med. 2007, 176, 1062–1071. [Google Scholar] [CrossRef] [PubMed]
- Büttner, C.; Lun, A.; Splettstoesser, T.; Kunkel, G.; Renz, H. Monoclonal anti-interleukin-5 treatment suppresses eosinophil but not T-cell functions. Eur. Respir. J. 2003, 21, 799–803. [Google Scholar] [CrossRef] [PubMed]
- Haldar, P.; Brightling, C.E.; Hargadon, B.; Gupta, S.; Monteiro, W.; Sousa, A.; Marshall, R.P.; Bradding, P.; Green, R.H.; Wardlaw, A.J.; et al. Mepolizumab and Exacerbations of Refractory Eosinophilic Asthma. N. Engl. J. Med. 2009, 360, 973–984. [Google Scholar] [CrossRef] [PubMed]
- Nair, P.; Pizzichini, M.M.M.; Kjarsgaard, M.; Inman, M.D.; Efthimiadis, A.; Pizzichini, E.; Hargreave, F.E.; O’Byrne, P.M. Mepolizumab for Prednisone-Dependent Asthma with Sputum Eosinophilia. N. Engl. J. Med. 2009, 360, 985–993. [Google Scholar] [CrossRef] [PubMed]
- Bel, E.H.; Wenzel, S.E.; Thompson, P.J.; Prazma, C.M.; Keene, O.N.; Yancey, S.W.; Ortega, H.G.; Pavord, I.D.; SIRIUS Investigators. Oral Glucocorticoid-Sparing Effect of Mepolizumab in Eosinophilic Asthma. N. Engl. J. Med. 2014, 371, 1189–1197. [Google Scholar] [CrossRef]
- Lugogo, N.; Domingo, C.; Chanez, P.; Leigh, R.; Gilson, M.J.; Price, R.G.; Yancey, S.W.; Ortega, H.G. Long-term Efficacy and Safety of Mepolizumab in Patients With Severe Eosinophilic Asthma: A Multi-center, Open-label, Phase IIIb Study. Clin. Ther. 2016, 38, 2058–2070.e1. [Google Scholar] [CrossRef]
- Khatri, S.; Moore, W.; Gibson, P.G.; Leigh, R.; Bourdin, A.; Maspero, J.; Barros, M.; Buhl, R.; Howarth, P.; Albers, F.C.; et al. Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma. J. Allergy Clin. Immunol. 2019, 143, 1742–1751.e7. [Google Scholar] [CrossRef]
- Cockle, S.M.; Stynes, G.; Gunsoy, N.B.; Parks, D.; Alfonso-Cristancho, R.; Wex, J.; Bradford, E.S.; Albers, F.C.; Willson, J. Comparative effectiveness of mepolizumab and omalizumab in severe asthma: An indirect treatment comparison. Respir. Med. 2017, 123, 140–148. [Google Scholar] [CrossRef]
- Pelaia, C.; Crimi, C.; Pelaia, G.; Nolasco, S.; Campisi, R.; Heffler, E.; Valenti, G.; Crimi, N. Real-life evaluation of mepolizumab efficacy in patients with severe eosinophilic asthma, according to atopic trait and allergic phenotype. Clin. Exp. Allergy 2020, 50, 780–788. [Google Scholar] [CrossRef]
- Crimi, C.; Campisi, R.; Cacopardo, G.; Intravaia, R.; Nolasco, S.; Porto, M.; Pelaia, C.; Crimi, N. Real-life effectiveness of mepolizumab in patients with severe refractory eosinophilic asthma and multiple comorbidities. World Allergy Organ. J. 2020, 13, 100462. [Google Scholar] [CrossRef]
- Crimi, C.; Campisi, R.; Nolasco, S.; Cacopardo, G.; Intravaia, R.; Porto, M.; Impellizzeri, P.; Pelaia, C.; Crimi, N. Mepolizumab effectiveness in patients with severe eosinophilic asthma and co-presence of bronchiectasis: A real-world retrospective pilot study. Respir. Med. 2021, 185, 106491. [Google Scholar] [CrossRef]
- Howarth, P.; Chupp, G.; Nelsen, L.M.; Bradford, E.S.; Bratton, D.J.; Smith, S.G.; Albers, F.C.; Brusselle, G.; Bachert, C. Severe eosinophilic asthma with nasal polyposis: A phenotype for improved sinonasal and asthma outcomes with mepolizumab therapy. J. Allergy Clin. Immunol. 2020, 145, 1713–1715. [Google Scholar] [CrossRef]
- Bleecker, E.R.; FitzGerald, J.M.; Chanez, P.; Papi, A.; Weinstein, S.F.; Barker, P.; Sproule, S.; Gilmartin, G.; Aurivillius, M.; Werkström, V.; et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): A randomised, multicentre, placebo-controlled phase 3 trial. Lancet 2016, 388, 2115–2127. [Google Scholar] [CrossRef]
- FitzGerald, J.M.; Bleecker, E.R.; Nair, P.; Korn, S.; Ohta, K.; Lommatzsch, M.; Ferguson, G.T.; Busse, W.W.; Barker, P.; Sproule, S.; et al. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2016, 388, 2128–2141. [Google Scholar] [CrossRef]
- FitzGerald, J.M.; Bleecker, E.R.; Menzies-Gow, A.; Zangrilli, J.G.; Hirsch, I.; Metcalfe, P.; Newbold, P.; Goldman, M. Predictors of enhanced response with benralizumab for patients with severe asthma: Pooled analysis of the SIROCCO and CALIMA studies. Lancet Respir. Med. 2018, 6, 51–64. [Google Scholar] [CrossRef]
- Chipps, B.E.; Newbold, P.; Hirsch, I.; Trudo, F.; Goldman, M. Benralizumab efficacy by atopy status and serum immunoglobulin E for patients with severe, uncontrolled asthma. Ann. Allergy Asthma Immunol. 2018, 120, 504–511.e4. [Google Scholar] [CrossRef]
- Nair, P.; Wenzel, S.; Rabe, K.F.; Bourdin, A.; Lugogo, N.L.; Kuna, P.; Barker, P.; Sproule, S.; Ponnarambil, S.; Goldman, M.; et al. Oral Glucocorticoid–Sparing Effect of Benralizumab in Severe Asthma. N. Engl. J. Med. 2017, 376, 2448–2458. [Google Scholar] [CrossRef]
- Busse, W.W.; Bleecker, E.R.; FitzGerald, J.M.; Ferguson, G.T.; Barker, P.; Sproule, S.; Olsson, R.F.; Martin, U.J.; Goldman, M.; BORA Study Investigators. Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial. Lancet Respir. Med. 2019, 7, 46–59. [Google Scholar] [CrossRef]
- Korn, S.; Bourdin, A.; Chupp, G.; Cosio, B.G.; Arbetter, D.; Shah, M.; Gil, E.G. Integrated Safety and Efficacy Among Patients Receiving Benralizumab for Up to 5 Years. J. Allergy Clin. Immunol. Pract. 2021, 9, 4381–4392.e4. [Google Scholar] [CrossRef]
- Pelaia, C.; Busceti, M.T.; Vatrella, A.; Rago, G.F.; Crimi, C.; Terracciano, R.; Pelaia, G. Real-life rapidity of benralizumab effects in patients with severe allergic eosinophilic asthma: Assessment of blood eosinophils, symptom control, lung function and oral corticosteroid intake after the first drug dose. Pulm. Pharmacol. Ther. 2019, 58, 101830. [Google Scholar] [CrossRef]
- Menzella, F.; Bonavia, M.; Bonini, M.; D’amato, M.; Lombardo, S.; Murgia, N.; Patella, V.; Triggiani, M.; Pelaia, G. Real-World Experience with Benralizumab in Patients with Severe Eosinophilic Asthma: A Case Series. J. Asthma Allergy 2021, 14, 149–161. [Google Scholar] [CrossRef] [PubMed]
- Scioscia, G.; Carpagnano, G.E.; Quarato, C.M.I.; Lacedonia, D.; Santamaria, S.; Soccio, P.; Depalo, A.; Fuso, P.; Foschino Barbaro, M.P. Effectiveness of Benralizumab in Improving the Quality of Life of Severe Eosinophilic Asthmatic Patients: Our Real-Life Experience. Front. Pharmacol. 2021, 12, 54. [Google Scholar] [CrossRef] [PubMed]
- Pelaia, C.; Crimi, C.; Benfante, A.; Caiaffa, M.F.; Calabrese, C.; Carpagnano, G.E.; Ciotta Jnr, D.; D’amato, M.; Macchia, L.; Nolasco, S.; et al. Therapeutic Effects of Benralizumab Assessed in Patients with Severe Eosinophilic Asthma: Real-Life Evaluation Correlated with Allergic and Non-Allergic Phenotype Expression. J. Asthma Allergy 2021, 14, 163–173. [Google Scholar] [CrossRef] [PubMed]
- Fernández, A.G.B.; Gallardo, J.F.M.; Romero, J.D.; Falcón, A.R.; Bernáldez, C.B.; Borrego, J.G.; Álvarez-Gutiérrez, F.J. Effectiveness of Switching to Benralizumab in Severe Refractory Eosinophilic Asthma. J. Asthma Allergy 2022, 15, 727–735. [Google Scholar] [CrossRef] [PubMed]
- Caruso, C.; Cameli, P.; Altieri, E.; Aliani, M.; Bracciale, P.; Brussino, L.; Caiaffa, M.F.; Canonica, G.W.; Centanni, S.; D’Amato, M.; et al. Switching from one biologic to benralizumab in patients with severe eosinophilic asthma: An ANANKE study post hoc analysis. Front. Med. 2022, 9, 2579. [Google Scholar] [CrossRef]
- Numata, T.; Miyagawa, H.; Nishioka, S.; Okuda, K.; Utsumi, H.; Hashimoto, M.; Minagawa, S.; Ishikawa, T.; Hara, H.; Araya, J.; et al. Efficacy of benralizumab for patients with severe eosinophilic asthma: A retrospective, real-life study. BMC Pulm. Med. 2020, 20, 207. [Google Scholar] [CrossRef]
- Drick, N.; Milger, K.; Seeliger, B.; Fuge, J.; Korn, S.; Buhl, R.; Schuhmann, M.; Herth, F.; Kendziora, B.; Behr, J.; et al. Switch from IL-5 to IL-5-Receptor α Antibody Treatment in Severe Eosinophilic Asthma. J. Asthma Allergy 2020, 13, 605–614. [Google Scholar] [CrossRef]
- Kavanagh, J.E.; Hearn, A.P.; d’Ancona, G.; Dhariwal, J.; Roxas, C.; Green, L.; Thomson, L.; Fernandes, M.; Kent, B.D.; Nanzer, A.M.; et al. Benralizumab after sub-optimal response to mepolizumab in severe eosinophilic asthma. Allergy 2021, 76, 1890–1893. [Google Scholar] [CrossRef]
- Martínez-Moragón, E.; García-Moguel, I.; Nuevo, J.; Resler, G.; The ORBE study investigators. Real-world study in severe eosinophilic asthma patients refractory to anti-IL5 biological agents treated with benralizumab in Spain (ORBE study). BMC Pulm. Med. 2021, 21, 417. [Google Scholar] [CrossRef]
- Ul-Haq, Z.; Naz, S.; Mesaik, M.A. Interleukin-4 receptor signaling and its binding mechanism: A therapeutic insight from inhibitors tool box. Cytokine Growth Factor Rev. 2016, 32, 3–15. [Google Scholar] [CrossRef]
- LaPorte, S.L.; Juo, Z.S.; Vaclavikova, J.; Colf, L.A.; Qi, X.; Heller, N.M.; Keegan, A.D.; Garcia, K.C. Molecular and Structural Basis of Cytokine Receptor Pleiotropy in the Interleukin-4/13 System. Cell 2008, 132, 259–272. [Google Scholar] [CrossRef]
- Gandhi, N.A.; Bennett, B.L.; Graham, N.M.H.; Pirozzi, G.; Stahl, N.; Yancopoulos, G.D. Targeting key proximal drivers of type 2 inflammation in disease. Nat. Rev. Drug Discov. 2015, 15, 35–50. [Google Scholar] [CrossRef]
- Le Floch-ramondou, A.; Nagashima, K.; Scott, G.; Birchard, D.; Asrat, S.; Bai, Y.; Lim, W.K.; Murphy, A.; Sleeman, M.; Orengo, J. Dual blockade of IL-4 and IL-13 with dupilumab, an IL-4Rα antibody, is required to broadly inhibit type 2 inflammation. J. Allergy Clin. Immunol. 2020, 145, AB158. [Google Scholar] [CrossRef]
- Boyce, J.A.; Mellor, E.A.; Perkins, B.; Lim, Y.C.; Luscinskas, F.W. Human mast cell progenitors use α4-integrin, VCAM-1, and PSGL-1 E-selectin for adhesive interactions with human vascular endothelium under flow conditions. Blood 2002, 99, 2890–2896. [Google Scholar] [CrossRef]
- Robinson, D.; Humbert, M.; Buhl, R.; Cruz, A.A.; Inoue, H.; Korom, S.; Hanania, N.A.; Nair, P. Revisiting Type 2-high and Type 2-low airway inflammation in asthma: Current knowledge and therapeutic implications. Clin. Exp. Allergy 2017, 47, 161–175. [Google Scholar] [CrossRef]
- Medrek, S.K.; Parulekar, A.D.; Hanania, N.A. Predictive Biomarkers for Asthma Therapy. Curr. Allergy Asthma Rep. 2017, 17, 69. [Google Scholar] [CrossRef]
- Ricciardolo, F.L.M.; Silkoff, P.E. Perspectives on exhaled nitric oxide. J. Breath Res. 2017, 11, 047104. [Google Scholar] [CrossRef]
- Beck, L.A.; Thaçi, D.; Hamilton, J.D.; Graham, N.M.; Bieber, T.; Rocklin, R.; Ming, J.E.; Ren, H.; Kao, R.; Simpson, E.; et al. Dupilumab Treatment in Adults with Moderate-to-Severe Atopic Dermatitis. N. Engl. J. Med. 2014, 371, 130–139. [Google Scholar] [CrossRef]
- Bachert, C.; Han, J.K.; Desrosiers, M.; Hellings, P.W.; Amin, N.; Lee, S.E.; Mullol, J.; Greos, L.S.; Bosso, J.V.; Laidlaw, T.M.; et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): Results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet 2019, 394, 1638–1650. [Google Scholar] [CrossRef]
- Wenzel, S.; Ford, L.; Pearlman, D.; Spector, S.; Sher, L.; Skobieranda, F.; Wang, L.; Kirkesseli, S.; Rocklin, R.; Bock, B.; et al. Dupilumab in Persistent Asthma with Elevated Eosinophil Levels. N. Engl. J. Med. 2013, 368, 2455–2466. [Google Scholar] [CrossRef]
- Wenzel, S.; Castro, M.; Corren, J.; Maspero, J.; Wang, L.; Zhang, B.; Pirozzi, G.; Sutherland, E.R.; Evans, R.R.; Joish, V.N.; et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: A randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet 2016, 388, 31–44. [Google Scholar] [CrossRef] [PubMed]
- Castro, M.; Corren, J.; Pavord, I.D.; Maspero, J.; Wenzel, S.; Rabe, K.F.; Busse, W.W.; Ford, L.; Sher, L.; FitzGerald, J.M.; et al. Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma. N. Engl. J. Med. 2018, 378, 2486–2496. [Google Scholar] [CrossRef] [PubMed]
- Busse, W.W.; Maspero, J.F.; Rabe, K.F.; Papi, A.; Wenzel, S.E.; Ford, L.B.; Pavord, I.D.; Zhang, B.; Staudinger, H.; Pirozzi, G.; et al. Liberty Asthma QUEST: Phase 3 Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate Dupilumab Efficacy/Safety in Patients with Uncontrolled, Moderate-to-Severe Asthma. Adv. Ther. 2018, 35, 737–748. [Google Scholar] [CrossRef] [PubMed]
- Rabe, K.F.; Nair, P.; Brusselle, G.; Maspero, J.F.; Castro, M.; Sher, L.; Zhu, H.; Hamilton, J.D.; Swanson, B.N.; Khan, A.; et al. Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma. N. Engl. J. Med. 2018, 378, 2475–2485. [Google Scholar] [CrossRef]
- Corren, J.; Castro, M.; O’Riordan, T.; Hanania, N.A.; Pavord, I.D.; Quirce, S.; Chipps, B.E.; Wenzel, S.E.; Thangavelu, K.; Rice, M.S.; et al. Dupilumab Efficacy in Patients with Uncontrolled, Moderate-to-Severe Allergic Asthma. J. Allergy Clin. Immunol. Pract. 2020, 8, 516–526. [Google Scholar] [CrossRef]
- Dupin, C.; Belhadi, D.; Guilleminault, L.; Gamez, A.S.; Berger, P.; De Blay, F.; Bonniaud, P.; Leroyer, C.; Mahay, G.; Girodet, P.O.; et al. Effectiveness and safety of dupilumab for the treatment of severe asthma in a real-life French multi-centre adult cohort. Clin. Exp. Allergy 2020, 50, 789–798. [Google Scholar] [CrossRef]
- Carpagnano, G.E.; Scioscia, G.; Buonamico, E.; Lacedonia, D.; Diaferia, F.; Capozza, E.; Lepore, G.; Resta, O.; Barbaro, M.P.F. Early effectiveness of type-2 severe asthma treatment with dupilumab in a real-life setting; a FeNO-driven choice that leads to winning management. Multidiscip. Respir. Med. 2022, 17, 797. [Google Scholar] [CrossRef]
- Pelaia, C.; Lombardo, N.; Busceti, M.T.; Piazzetta, G.; Crimi, C.; Calabrese, C.; Vatrella, A.; Pelaia, G. Short-Term Evaluation of Dupilumab Effects in Patients with Severe Asthma and Nasal Polyposis. J. Asthma Allergy 2021, 14, 1165. [Google Scholar] [CrossRef]
- Mümmler, C.; Munker, D.; Barnikel, M.; Veit, T.; Kayser, M.Z.; Welte, T.; Behr, J.; Kneidinger, N.; Suhling, H.; Milger, K. Dupilumab Improves Asthma Control and Lung Function in Patients with Insufficient Outcome During Previous Antibody Therapy. J. Allergy Clin. Immunol. Pract. 2021, 9, 1177–1185.e4. [Google Scholar] [CrossRef]
- Campisi, R.; Crimi, C.; Nolasco, S.; Beghè, B.; Antonicelli, L.; Guarnieri, G.; Scichilone, N.; Porto, M.; Macchia, L.; Scioscia, G.; et al. Real-World Experience with Dupilumab in Severe Asthma: One-Year Data from an Italian Named Patient Program. J. Asthma Allergy 2021, 14, 575. [Google Scholar] [CrossRef]
- Numata, T.; Araya, J.; Miyagawa, H.; Okuda, K.; Takekoshi, D.; Hashimoto, M.; Minagawa, S.; Ishikawa, T.; Hara, H.; Kuwano, K. Real-World Effectiveness of Dupilumab for Patients with Severe Asthma: A Retrospective Study. J. Asthma Allergy 2022, 15, 395. [Google Scholar] [CrossRef] [PubMed]
- Eger, K.; Pet, L.; Weersink, E.J.M.; Bel, E.H. Complications of switching from anti–IL-5 or anti–IL-5R to dupilumab in corticosteroid-dependent severe asthma. J. Allergy Clin. Immunol. Pract. 2021, 9, 2913–2915. [Google Scholar] [CrossRef] [PubMed]
- Briegel, I.; Felicio-Briegel, A.; Mertsch, P.; Kneidinger, N.; Haubner, F.; Milger, K. Hypereosinophilia with systemic manifestations under dupilumab and possibility of dual benralizumab and dupilumab therapy in patients with asthma and CRSwNP. J. Allergy Clin. Immunol. Pract. 2021, 9, 4477–4479. [Google Scholar] [CrossRef] [PubMed]
- Hirano, T.; Matsunaga, K. Late-onset asthma: Current perspectives. J. Asthma Allergy 2018, 11, 19. [Google Scholar] [CrossRef]
Study | Study Type | Switch | Study Population | Results |
---|---|---|---|---|
Chapman et al. [24], 2019 (OSMO study) | Clinical trial | From Omalizumab to Mepolizumab (observation: 36 weeks) | 138 patients affected by allergic eosinophilic asthma with a suboptimal response to Omalizumab were switched to Mepolizumab | Clinically significant improvements in asthma control, health status, and exacerbation rate, with no tolerability issues reported. |
Liu et al. [29], 2021 | Post hoc analysis of OSMO study | From Omalizumab to Mepolizumab (observation: 36 weeks) | Subgroup analyses of patients included in the OSMO study (n = 138) to evaluate the influence of baseline characteristics (blood eosinophil count, comorbidities, exacerbation history, oral corticosteroid use, ACQ-5 and SGRQ scores, body mass index) on the results of the switch from Omalizumab to Mepolitzumab | Improvements were observed regardless of baseline characteristics. |
Magnan et al. [30], 2016 | Post hoc analyses of MENSA and SIRIUS studies | From Omalizumab to Mepolizumab (observation: 32 weeks in MENSA and 20 weeks in SIRIUS) | Post hoc analyses to assess the effectiveness of Mepolizumab in patients with severe eosinophilic asthma previously treated with Omalizumab included in the MENSA (75 patients, 13%) and SIRIUS (45 patients, 33%) studies | Patients responded positively to Mepolizumab regardless of prior use of Omalizumab. |
Bagnasco et al. [35], 2019 | Real-life study | From Omalizumab to Mepolizumab (observation: 1 year) | 27 patients with severe allergic eosinophilic asthma were switched to Mepolizumab due to lack of control despite Omalizumab treatment | Significant reduction in mean yearly exacerbations and mean dose of OCS (daily mg of prednisone) and significant improvement in mean FEV1 and mean ACT score. |
Carpagnano et al. [36], 2020 | Real-life study | From Omalizumab to Mepolizumab (observation: 1 year) | 41 patients with severe allergic eosinophilic asthma, with previous unsuccessful anti-IgE treatment, were switched to Mepolizumab without a washout period. | Increase in ACT score and in pre-bronchodilator FEV1, with a reduction in exacerbations and blood eosinophils. The percentage of patients who were dependent on corticosteroids also lowered. |
Carpagnano et al. [37], 2021 | Real-life study | From Omalizumab to Mepolizumab (observation: 1 year) | 33 patients with severe eosinophilic asthma undergoing a switch to Mepolizumab because they were not optimally controlled by Omalizumab | Decrease in annual exacerbations and adverse events related to prolonged OCS consumption with a consequent reduction in the number of lost working days. |
Pelaia et al. [38], 2021 | Real-life study | From Omalizumab to Benralizumab (observation: 1 year) | 20 patients with severe persistent allergic and eosinophilic asthma, uncontrolled despite the add-on biological treatment with Omalizumab, and thus switched to Benralizumab. | Significant improvements in asthma exacerbation rate, rescue medication need, ACT score, FEV1 and blood eosinophil count. |
O’Reilly et al. [39], 2022 | Real-life study | From Omalizumab to anti-IL5 or anti-IL5Rα therapy (observation: 1 year) | 10 patients switched to an anti-IL-5 therapy (6 patients switched to Benralizumab and 4 to Mepolizumab) due to suboptimal control despite Omalizumab | Significant reductions in community exacerbation rate and serum eosinophil count and a significant improvement in FEV1 from baseline. |
Gómez-Bastero Fernández et al. [65], 2022 | Real-life study | From Omalizumab to anti-IL5 or anti-IL5Rα therapy (observation: 4 and 12 months) | 40 patients switched from Omalizumab (n = 16) or Mepolizumab (n = 24) to Benralizumab due to lack of response (30 cases), adverse effects (9 cases) or patient request (1 case) | Significant decrease in the number of exacerbations, visits to the emergency department, and corticosteroid cycles. ACT score also improved. However, no significant improvement in lung function was observed. |
Caruso et al. [66], 2022 | Post hoc analysis of the ANANKE study (real-life study) | From Omalizumab or Mepolizumab to Benralizumab (observation: 16, 24 and 48 weeks) | 147 biologic-naïve and 58 biologic-experienced asthma patients (34 Omalizumab, 19 Mepolizumab, and 5 Omalizumab-Mepolizumab) were observed after Benralizumab introduction | Similar reductions in exacerbations (>90% in both groups), OCS use (≥49% reduction in OCS dosage), ACT improvement and lung function were observed within the two groups. |
Numata et al. [67], 2020 | Real-life study | From Mepolizumab to Benralizumab (observation: 4 months) | Among 24 patients treated with Mepolizumab, 11 had directly switched to Benralizumab due to a lack of asthma control | Slightly improvement in some parameters, but without significant differences. |
Drick et al. [68], 2020 | Real-life study | From anti-IL5 therapy to anti-IL-5Rα (observation: 5 months) | Among 665 asthmatic subjects receiving anti-IL5 treatment, 60 patients (12 receiving Reslizumab and 48 receiving Mepolizumab) were switched to Benralizumab | Progressive improvement in symptom control, OCS intake and lung function. |
Kavanagh et al. [69], 2021 | Real-life study | From Mepolizumab to Benralizumab (observation: 48 weeks) | 33 asthmatic patients with an unsatisfactory response to Mepolizumab underwent a switch to Benralizumab | Reduction in the annualized exacerbation rate by 58%, significant improvement in symptom control and quality of life, and increase in the percentage of patients who achieved a ≥50% OCS dose decrement. However, no significant increase in FEV1 compared with baseline values. |
Martínez-Moragón et al. [70], 2021 (ORBE study) | Real-life study | From anti-IL5 therapy to anti-IL5Rα (observation: until a mean of 5 months between the first and the last Benralizumab treatment dosage) | 24 subjects previously treated with Mepolizumab and 3 patients previously treated with Reslizumab were shifted to Benralizumab due to lack of efficacy | Significant improvements in ACT score, annualized asthma exacerbation rate, and OCS intake occurred. No significant FEV1 increase was detected. |
Mümmler et al. [90], 2021 | Real-life study | From anti-IgE or anti-IL5/IL5Rα therapies to Dupilumab (observation: from 3 to 6 months) | 38 severe asthma patients were switched to Dupilumab from a previous anti-IgE or anti-IL5/IL5Rα medication due to insufficient outcome | 32 out of 38 patients, improved asthma control and lung function, decreased exacerbation rate, and FENO and IgE levels. Patients with increased FENO (≥25 ppb) during previous antibody therapy were more often responders to Dupilumab than patients with lower FENO (<25 ppb). |
Campisi et al. [91], 2021 | Real-life study | From Omalizumab, Mepolizumab or Benralizumab to Dupilumab (observation: 12 months) | 5 patients were switched from Omalizumab, Mepolizumab, or Benralizumab to Dupilumab due to a lack of therapeutic response | Reduction in the number of exacerbations and OCS use, as well as improvement in pre-bronchodilator FEV1% values and asthma control in all the subjects. |
Numata et al. [92], 2022 | Real-life study | From Omalizumab, Mepolizumab or Benralizumab to Dupilumab (observation: mean follow-up of 12.6 months) | 10 patients received Dupilumab as the first biologic, and 16 switched to Dupilumab from other biologics | Reduction in exacerbations and OCS maintenance doses and improvement in asthma symptoms regardless of prior biologic treatment. The baseline blood eosinophil count (≥150 cells/µL before Dupilumab administration or ≥300 cells/µL prior to the use of any biologics) seemed to identify “super responders” to Dupilumab. |
Eger et al. [93], 2021 | Case series | From anti-IL-5 or anti IL-5Rα biologics to Dupilumab (observation: variable case by case) | 4 patients previously treated with an anti-IL-5 or anti-IL-5R biologic for OCS-dependent asthma who were switched to Dupilumab | The switch to Dupilumab, together with discontinued OCS use, induced hypereosinophilia, with sudden deterioration of asthma, tissue infiltration by eosinophils, and EGPA-like symptoms, such as thromboembolic events. |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Scioscia, G.; Nolasco, S.; Campisi, R.; Quarato, C.M.I.; Caruso, C.; Pelaia, C.; Portacci, A.; Crimi, C. Switching Biological Therapies in Severe Asthma. Int. J. Mol. Sci. 2023, 24, 9563. https://doi.org/10.3390/ijms24119563
Scioscia G, Nolasco S, Campisi R, Quarato CMI, Caruso C, Pelaia C, Portacci A, Crimi C. Switching Biological Therapies in Severe Asthma. International Journal of Molecular Sciences. 2023; 24(11):9563. https://doi.org/10.3390/ijms24119563
Chicago/Turabian StyleScioscia, Giulia, Santi Nolasco, Raffaele Campisi, Carla Maria Irene Quarato, Cristiano Caruso, Corrado Pelaia, Andrea Portacci, and Claudia Crimi. 2023. "Switching Biological Therapies in Severe Asthma" International Journal of Molecular Sciences 24, no. 11: 9563. https://doi.org/10.3390/ijms24119563