Durability of benralizumab effectiveness in severe eosinophilic asthma patients with and without chronic rhinosinusitis with nasal polyps (CRSwNP): a post hoc analysis from the ANANKE study

Luisa Brussino ¹ Maria Aliani ² Elena Altieri ³ Pietro Bracciale ⁴ Maria Filomena Caiaffa ⁵ Paolo Cameli ⁶ Giorgio Walter Canonica ^7,8 Cristiano Caruso ^10,9 Stefano Centanni ¹¹ Fausto De Michele ¹² Stefano R Del Giacco ¹³ Fabiano Di Marco ¹⁴ Laura Malerba ¹⁵ Francesco Menzella ¹⁶ Girolamo Pelaia ¹⁷ Paola Rogliani ^18,19 Micaela Romagnoli ²⁰ Pietro Schino ²¹ Jan Walter Schroeder ²² Gianenrico Senna ²³ Alessandra Vultaggio ²⁴ Maria D'Amato ^25,26*

• ¹ Dipartimento di Scienze Mediche, Università degli Studi di Torino; SCDU Immunologia e Allergologia, AO Ordine Mauriziano Umberto I, Torino, Italy
• ² UO Pneumologia e Pneumologia Riabilitativa, ICS Maugeri, IRCCS Bari, Bari, Italy
• ³ Reparto di Pneumologia, P.O. Garbagnate Milanese, Garbagnate Milanese (MI), Italy
• ⁴ Reparto di Pneumologia, Ospedale Ostuni, Ostuni (BR), Italy
• ⁵ Cattedra e Scuola di Allergologia e Immunologia Clinica, Dipartimento di Scienze Mediche, Università di Foggia, Foggia, Italy
• ⁶ Respiratory Diseases Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
• ⁷ Department of Biomedical Sciences, Humanitas University, Siena, Italy
• ⁸ Personalized Medicine Center: Asthma and Allergology, Humanitas Research Hospital, Rozzano (MI), Italy
• ⁹ UOSD Allergy and Clinical Immunology, Fondazione Policlinico A. Gemelli, IRCCS, Roma, Italy
• ¹⁰ UOC Internal Medicine Fondazione Gemelli Isola, Roma, Italy
• ¹¹ Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, Università degli Studi di Milano, Milano, Italy
• ¹² UOC Pneumologia e Fisiopatologia Respiratoria, AORN A. Cardarelli, Napoli, Italy
• ¹³ Dipartimento di Scienze Mediche e Sanità Pubblica, Università degli Studi di Cagliari, Monserrato (CA), Italy
• ¹⁴ Department of Health Sciences, Università degli Studi di Milano, Pneumologia, ASST Papa Giovanni XXIII, Bergamo, Italy
• ¹⁵ Medical Affairs R&I, Astrazeneca, Milano, Italy
• ¹⁶ Pulmonology Unit, Ospedale “S. Valentino”, AULSS 2 Marca Trevigiana, Montebelluna (TV), Italy
• ¹⁷ Dipartimento di Scienze della Salute, Università Magna Graecia, Catanzaro, Italy
• ¹⁸ Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome "Tor Vergata", Roma, Italy
• ¹⁹ Division of Respiratory Medicine, University Hospital "Fondazione Policlinico Tor Vergata", Roma, Italy
• ²⁰ UOC Pneumologia, AULSS 2 Marca Trevigiana, Treviso, Italy
• ²¹ Fisiopatologia Respiratoria, Ospedale Generale Regionale, Ente Ecclesiastico "F. Miulli", Acquaviva delle Fonti (BA), Italy
• ²² Allergy and Clinical Immunology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
• ²³ Allergy Unit and Asthma Center, Verona University Hospital, Verona, Italy
• ²⁴ Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Firenze, Italy
• ²⁵ Hospital of the Hills, Naples, Italy
• ²⁶ UOSD Malattie Respiratorie “Federico II”, Ospedale Monaldi, AO Dei Colli, Napoli, Italy

Severe eosinophilic asthma (SEA) often co-occurs with chronic rhinosinusitis with nasal polyps (CRSwNP), worsening asthma symptoms. Earlier studies have shown that benralizumab improves asthma outcomes with greater efficacy if patients present CRSwNP. This post hoc analysis of the ANANKE study (NCT04272463) reports data on the long-term effectiveness of benralizumab between SEA patients with and without CRSwNP (N=86 and N=75, respectively) treated for up to 96 weeks. Before benralizumab initiation, CRSwNP patients displayed longer SEA duration, greater oral corticosteroid (OCS) use and blood eosinophil count. After 96 weeks of treatment, the annual exacerbation rate (AER) decreased in both groups, with CRSwNP patients achieving considerable reductions than No-CRSwNP patients (severe AER dropped by 100% and 95.6%, respectively). While lung function improvement was comparable at week 96, CRSwNP patients showed a faster response to benralizumab, with a rise of forced expiratory volume in 1 second (FEV1) at 16 weeks that was maintained throughout the study. Median OCS daily dose decreased to 0.0 mg in both groups at 96 weeks, but benralizumab OCS-sparing effect was faster in CRSwNP patients (median OCS dose was 0.0 mg and 2.5 mg in CRSwNP and No-CRSwNP patients respectively, at 48 weeks). Although asthma control test (ACT) median scores were comparable, greater proportions of CRSwNP patients displayed well-controlled asthma (ACT≥20) than No-CRSwNP patients at all time points. These findings show benralizumab longterm effectiveness in SEA patients with and without CRSwNP, highlighting its superior and fasteracting benefits on asthma outcomes in presence of CRSwNP.