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.

Table.FEOS scores according to the presence or absence of

Introduction: REDES was a multicenter, retrospective, observational, real world study on the effectiveness and safety of 100 mg SC mepolizumab in Severe Eosinophilic Asthma (SEA) patients in Spain (n=318). Methods: This post hoc analysis described the demographic features and mepolizumab effectiveness according to the presence or absence of comorbid NP, a condition commonly present in an eosinophilic severe asthmatic phenotype. Results: 147 (46.2%) patients had a diagnosis of comorbid NP, with baseline eosinophils levels of 799 eos/µL (SEA without NP: 634 eos/µL). After 12 months of mepolizumab therapy, SEA+NP patients experienced an 83.4% reduction in annual exacerbation rates (SEA without NP: 73.0%, p=0.0017) and 53.7% of patients requiring maintenance therapy with oral corticosteroids were able to completely discontinue (SEA without NP: 42.9%). At the end of the year, all SEA patients also had improved asthma control, 76.0% with ACT>20 in SEA+NP vs 69.8% in SEA without NP, and improved their lung function: 0.23L in FEV1 (pre-BD) in SEA+NP vs 0.18L in SEA without NP (intergroup p=ns). Conclusion: Whilst mepolizumab is an effective treatment for SEA patients with and without a diagnosis of comorbid NP, those with SEA+NP represent a clinical phenotype who respond particularly well to mepolizumab therapy. Funding:GSK (ID 213172)

Servei de Pneumologia i Al·lèrgia. Hospital de la Santa Creu i Sant Pau. Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau). Universitat Autònoma de Barcelona. Barcelona Medicina de Familia. Centro de Salud de Menasalbas. Menasalbas, Toledo Servicio de Neumología. Hospital Universitario de La Princesa. Instituto de Investigación La Princesa Madrid Servicio de Alergología. Instituto de Investigación Hospital Universitario La Paz (IdiPAZ). CIBER de Enfermedades Respiratorias (CIBERES). Madrid Área de Alergología del Hospital Universitario Virgen del Rocío. Sevilla Sevicio de Alergología. Hospital Universitario Río Hortega. Valladolid Sección de Alergología. Hospital Nuestra Señora de la Montaña. Cáceres Servicio de Alergología. Hospital Clínico Universitario Virgen de la Arrixaca. Murcia Servicio de Neumología. Hospital Universitario Valld’Hebron. Barcelona Unidad de Neumología. Agencia Sanitaria Costa del Sol. Marbella, Málaga Servicio de Neumología. Servizo Galego de Saúde. Servicio de Neumología. Hospital Arnau Vilanova. Valencia Servicio de Neumología. Hospital de la Santa Creu i Sant Pau. Barcelona Unidad de Asma y Enfermedades Ocupacionales-Medioambientales del Servicio de Neumología. Hospital Galdakao-Usansolo. Galdakao, Bizkaia Servicio de Alergología. Instituto de Investigación Hospital Universitario La Paz (IdiPAZ) y CIBER de Enfermedades Respiratorias (CIBERES). Madrid