Real-World Effectiveness and the Characteristics of a 'Super-Responder' to Mepolizumab in Severe Eosinophilic Asthma.

Mepolizumab was the first licensed anti-IL5 mAb for severe eosinophilic asthma (SEA). To date there is little data to confirm its efficacy in the real-world setting or assessment of baseline characteristics associated with response.We conducted a retrospective review of all patients who received at least 16 weeks of treatment with mepolizumab (100mg sc) for SEA at our regional asthma centre in the UK. Clinical data was collected at each 4-weekly visit. At 16, 24 and 52 weeks, patients were classified as 'responders' or 'non-responders'. A response was defined as ≥50% reduction in exacerbations, or for patients requiring maintenance oral corticosteroids (mOCS), ≥50% reduction in prednisolone dose. Super-responders were defined as exacerbation-free and off mOCS at one year.99 patients were included in the analysis. Asthma exacerbations decreased from a baseline of 4.04(2.57) to 1.86(2.17) at 1 year (54% reduction, p<0.001). 68 subjects were on mOCS at the time of commencing mepolizumab. By one year the daily median dose fell from 10mg (IQR 10-15) to 0mg (IQR 0-10, p<0.001). 57% were able to discontinue mOCS. 72.7% (95%CI 63.0-80.7) patients were classified as responders and 28.3% (95%CI 20.2-38.0) as super-responders. Baseline characteristics associated with responder and super-responder status included: the presence of nasal polyposis (p=0.012), lower baseline ACQ6 (p=0.006), a lower BMI (p=0.014), and in those on mOCS a significantly lower prednisolone dose at baseline (p=0.005). At 16 weeks, the 1-year responder status was correctly identified in 80.8% patients and by 24 weeks this rose to 92.9%.In a real-world SEA cohort, treatment with mepolizumab reduced exacerbation frequency and mOCS requirements. Nasal polyposis, a lower BMI and a lower maintenance prednisolone requirement at baseline were associated with better outcomes. Twelve-month response was identifiable in over 90% of patients by week 24.

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