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Type of article: Original article
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Real-world long-term multicentric study of primary and secondary failure to biologicals in severe asthma
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D Dacal Rivas1, E Martinez-Moragón2, V Plaza3, C Cisneros Serrano4, C Benchimol3, H Izaguirre Flores5, S Sánchez-Cuéllar6, MD Martínez-Pitarch7, C Fernández Aracil8, A Trisán Alonso9, JC Serrano Rebollo10, Z Vásquez Gambasica11, RM Díaz Campos12, P Trujillo Mulato13, I Escribano Gimeno14, D Laorden15, E Arismendi16, N Marina Malanda17, A De Diego Damia18, M Ferrer Galvan19..., I Dávila20, J Ortiz de Saracho Bobo21, BG Cosio22, LA Pérez de Llano23,
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eremos26@hotmail.com

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1 Pneumology Service. Lucus Augusti University Hospital. EOXI Lugo, Monforte, Cervo. Lugo. Spain. University of Santiago de Compostela, Spain
2 Pneumology Service. Doctor Peset University Hospital, Valencia, Spain
3 Servicio de Neumología y Alergia. Hospital de la Santa Creu i Sant Pau, Barcelona. Universidad Autónoma Barcelona, Facultad de Medicina, Barcelona, Spain
4 Pneumology Service. La Princesa University Hospital. Instituto de investigación La Princesa, Madrid, Spain
5 Servicio de Neumología. Complejo Hospitalario Universitario de Canarias, Las Palmas, Spain
6 Servicio de Neumologia. Hospital Universitario Ramón y Cajal, Madrid, Spain
7 Hospital Lluís Alcanys de Xátiva, Valencia, Spain
8 Servicio de Neumología, Hospital General Universitario Dr. Balmis; Universidad Miguel Hernández; Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
9 Pneumology Service. Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain
10 Hospital de Llerena-Zafra, Spain
11 Hospital Universitario de Getafe, Madrid, Spain
12 Servicio de Neumología. Hospital Universitario 12 de Octubre, Madrid, Spain
13 Instituto Nacional del Tórax, Santiago de Chile, Chile
14 Hospital Infanta Sofía. San Sebastián de los Reyes, Madrid, Spain
15 Department of Pulmonology, La Paz University Hospital, Madrid, Spain
16 Servei de Pneumologia del Hospital Clínic de Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain CIBERES, Instituto de Salud Carlos III, Spain
17 Dpto Neumología, Unidad de Asma Grave, Hospital Universitario Cruces, Bilbao, Spain
18 Area de Enfermedades Respiratorias. Hospital Universitario y Politécnico La Fe, Valencia, Spain
19 Pneumology Service. Hospital Universitario Virgen del Rocío, Sevilla, Spain
20 Servicio de Alergia, Hospital Universitario de Salamanca, Spain. Departamento de Ciencias Biomédicas y del Diagnóstico, Facultad de Medicina, Universidad de Salamanca, Salamanca, Spain
21 Pneumology Service. Hospital Universitario del Bierzo, Ponferrada, Spain
22 Department of Respiratory Medicine. Hospital Universitario Son Espases-IdISBa-CIBERES, Palma de Mallorca, Spain
23 Pneumology Service. Lucus Augusti University Hospital. EOXI Lugo, Monforte, Cervo. Lugo. Spain. Associate Professor, University of Santiago de Compostela, Spain
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Abstract

Objectives: Only one-third of patients with severe asthma (SA) achieve a complete response to biologics. This study aims to characterize two types of failure: early (EF), occurring ≤ 12 months after biologic initiation, and late (LF), occurring at any time during follow-up after response has been achieved at 12 months.

Methods: This is a multicentre retrospective study of adults treated with the same biologic for ≥24 months. Response was defined as no severe exacerbations in the preceding 12 months, Asthma Control Test ≥20, and no need for maintenance oral corticosteroids. Failure (EF or LF) was defined as non-achievement of any of these objectives.

Results: Two hundred and seventy-two patients were analysed with a mean follow-up of 46.1 ± 19.4 months. At 12 months, 97/272 were classified as PF, but 40% of them recovered response on subsequent visits (by changing inhaled therapy in 74%). Among the 175 responders at 12 months, 124 (70.8%) maintained response throughout the study period, while 51 (29.1%) experienced SF; those patients had lower FEV1 values after 12 months of biological therapy. SF reverted in 36% of cases, with inhaled therapy changes in 41.6%. FEV1 decreased by ≥100 mL in 12 of 16 cases who did not recover response after SF.

Conclusion: Most patients who achieve response at 12 months maintain it over time, but 29% of them suffer LF. Optimization of inhaled therapy can aid response recovery from EF or LF. Maximizing pulmonary function helps to prevent loss of response.

Keywords:
severe asthma
biologics
early failure
late failure
long-term study
treatment response
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