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

Abstract

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.