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Response to monoclonal antibodies in asthma: definitions, potential reasons for failure and therapeutic options for suboptimal response

Pérez de Llano L1, Cisneros C2,3, Domínguez-Ortega J4,5, Martínez-Moragón E6, Olaguibel JM5,7,8, Plaza V5,9,10,11, Quirce S4,5, Dávila I12,13,14

1Respiratory Service, Hospital Universitario Lucus Augusti. EOXI Lugo, Monforte, Cervo, Spain
2Respiratory Medicine Department, Hospital La Princesa, Madrid, Spain
3Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain
4Department of Allergy, La Paz University Hospital, IdiPAZ, Madrid, Spain
5CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain
6Respiratory Service, Hospital Universitario Dr Peset, Valencia, Spain
7Allergy Department, Hospital Universitario de Navarra. Pamplona, Spain
8Instituto de Investigaciones de Navarra (IDISNA), Pamplona, Spain
9Respiratory Medicine Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
10Institut de Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, Spain
11Facultad Medicina, Universitat Autonoma Barcelona, Spain
12Allergy Service, Hospital Universitario de Salamanca, Spain
13Instituto de Investigación Biosanitaria de Salamanca (IBSAL), Salamanca, Spain
14Departamento de Ciencias Biomédicas y del Diagnóstico. Facultad de Medicina, Universidad de Salamanca, Salamanca, Spain

J Investig Allergol Clin Immunol 2023; Vol. 33(1)
doi: 10.18176/jiaci.0857

Real-life data reveal that more than half of severe asthma patients treated with monoclonal antibodies (mAbs) do not achieve a complete response. Response to mAbs must be assessed holistically, considering all the clinically meaningful therapeutic goals, not just exacerbations or oral corticosteroid reduction. There are two different ways of measuring the response to mAbs: one, qualitative, classifies patients according to the degree of disease control they have achieved, without explaining how much a given patient improves relative to his baseline (pre-mAb) clinical situation; the other, quantitative, scores the changes occurred after treatment. Both methods are complementary and essential to making clinical decisions on whether to continue treatment. Several potential causes of suboptimal response to mAbs have been described: incorrect identification of the specific T2 pathways, comorbidities that reduce the room for improvement, insufficient dose, autoimmune phenomena, infections, change of the initial inflammatory endotype, and adverse events. Once a suboptimal response has been confirmed, a well-structured and multifaceted assessment of the potential causes of failure should be performed, considering, in particular, the resulting inflammatory process of the airway after mAb therapy and the presence of chronic or recurrent infection. This investigation should guide the decision on the best therapeutic approach. This review aims to help clinicians gain insights into how to measure response to mAbs and proceed in suboptimal response cases. 

Key words: Severe asthma, Omalizumab, Mepolizumab, Reslizumab, Benralizumab, Dupilumab, Tezepelumab, Response