Clinical parameters and blood biomarkers associated with response to mepolizumab in severe asthma

Background Mepolizumab is effective for a subset of severe asthma patients in reducing exacerbation frequency. Identification of an early marker associated with long-term beneficial clinical response would facilitate better targeting of treatment. We set out to determine the impact of mepolizumab from a clinical, blood inflammatory cell and serum proteomics perspective and identify early changes in patients designated responder/non-responder at one year. Methods We enrolled asthma patients that met criteria to be prescribed mepolizumab. Patients had clinical and blood cell measurements at baseline, 12 and 26 weeks. Serum proteomics (Alamar NULISA, 250 panel) was completed at baseline and 12 weeks. Results 37 patients completed the study (24 and 13 responder and non-responder respectively at 1 year). Both Asthma Control Questionnaire (ACQ)-6 and Severe Asthma Questionnaire (SAQ) improved at 12 and 26 weeks and were driven by the responder group. A reduction in blood eosinophils and basophils was observed. There was a significant elevation of only 2/248 serum proteins, IL5 and CCL24 after 12 weeks mepolizumab treatment, with elevation being driven by the responder and non-responder groups respectively. A 12-week improvement in SAQ was associated with higher odds of response at one year (OR 6.75, 95% CI 1.42–24.30; p=0.015). Conclusions We identified early changes in the clinical and protein profile in patients that go onto have a clinically relevant response to mepolizumab providing opportunities for a more personalised asthma management.