Patients with severe uncontrolled asthma (SUA) may have a variable response to biological therapy (BT). A precise biomarker of response to BT is still lacking. We hypothesize that serum miRNA profiles can identify patients who achieve a complete response after 6 months of BT.

Objectives: to evaluate the profile of serum miRNAs predictive of complete response to BT in a population with SUA.

Methods.Prospective study that includes patients with SUA candidates for BT whose clinical variables associated to clinical response and serum samples were collected prior (V1) to BT and after 6 months (V2). Responder was defined as ?1 exacerbation and fulfilling at least one of the following criteria: ?10% or ?100 mL improvement in FEV1 or ?4 points on the asthma control test (ACT) at V2. Non-responder was defined as ?2 exacerbations. Partial responders were those who did not meet the responder or non-responder criteria. Serum miRNAs were extracted and hybridized on the Affymetrix GeneChip miRNA and compared between different responses.

Results. 30 patients were included (4 T2 allergic asthma and 26 T2 eosinophilic asthma phenotypes)). A complete response to BT was observed in 20 patients (66%), a partial response in 6 (20%) and no response in 4 patients (14%). One patient (3%) was treated with omalizumab, 7 (24%) with mepolizumab, 19 (63%) with benralizumab, and 3 (10%) with reslizumab. 3 miRNAs (miR-6803-5p, miR-4281 and miR-7108-5p; p<0.05) were differentially expressed in V1 vs V2 responders whereas no different expression was observed between non-responders.

Conclusions. The differential expression of serum miRNAs miR-6803-5p, miR-4281 and miR-7108-5p could identify responders to BT.