The role of bronchial biopsy in the prediction of response to biological therapy in severe uncontrolled asthma: a prospective study

Background: Up to two thirds of patients with severe uncontrolled asthma (SUA) who received biological therapy do not have a complete response.

Research question: Can bronchial biopsy (BB) play a role in the identification of patients with SUA who has a better response to biological therapy?

Study design: AND METHODS: Prospective multicentre study. Consecutive SUA patients candidate to biological therapy underwent bronchoscopy and BB prior to biological therapy and clinical response was evaluated 6 months later. BB was evaluated according to a previously validated pathological score (PS) and was compared with a score of T2 inflammation (T2 score) that includes blood eosinophil count (BEC) and FeNO in predicting response to biological therapy. Response was graded as super-response, good response and partial/no response according to a composite score that includes exacerbations, oral corticosteroid (OCS) use, asthma control test (ACT) and improvement in FEV1.

Results: 92 patients were recruited and 78 completed the study, 63 of them received anti-IL5/5R (Mepolizumab, Reslizumab and Benralizumab) and 15 Dupilumab, being super-responders 36.5% and 26.6% respectively (p=0.126). The PS, but not the T2 score, was the only variable independently associated to response. Super-responders showed statistically significant higher PS. Response was better predicted by the PS compared to T2 score, in those receiving OCS and especially in those on anti-IL5/5R . Low tissue eosinophilia (<10 eosinophils/field) was associated to poor response to biological therapy.

Interpretation: BB is more precise in the prediction of response to biological therapy than the T2 score, especially in those requiring OCS or receiving anti-IL5/5R . Tissue eosinophilia is the main driver of this predictive capacity, but there are other items in the PS related to bronchial remodeling that might be contributing to the identification of response to biological therapy.