Late Breaking Abstract - Phenotyping Mepolizumab EXacerbations in severe eosinophilic asthma (MEX)

Background: Clinical trials with anti-IL5 therapies show a 50% reduction in severe asthma exacerbations; exacerbations on mepolizumab appear different from placebo questioning their inflammatory phenotype and physiological characteristics.

Methods: Observational study in mepolizumab treated patients (n=145) at 4 UK Severe Asthma Specialist clinics. Patients attended study centre for exacerbation assessment pre-treatment.

Results: 172 exacerbations with 96 assessed pre-treatment; peak flow & symptoms diaries showed no difference in assessed & missed exacerbations. At initial exacerbation/participant, 45/69 (65%) produced sputum of whom 47% were sputum eosinophil (SE) high ≥2% & 53% were SE low <2%. SE≥2% were FeNO high (57[30,111] vs 24[16,45] ppb, p<0.001), had low FEV1% predicted (56(15) vs 72(21), p=0.008), obstructive spirometry (FEV1/FVC% 58(14) vs 68(9), p=0.004), higher blood eosinophils (70[50,90] vs 30[10,50]cells/µL, p<0.001) and median SE 10%[5,21] vs 0.4%[0.2, 0.8], p<0.001. In contrast, SE<2% exacerbations were FeNO low, CRP high (15[5,24] vs 2.3[2,5] mg/L, p <0.001), with sputum neutrophilia (90%[72, 95] vs 37%[29,54], p<0.001) and 50% receiving antibiotics (v 19% in SE≥2%, p0.03). FeNO (<20 or ≥50ppb) was a useful discriminator.

Conclusion: Exacerbations on mepolizumab are 2 distinct entities; non-eosinophilic events are driven by infection & FeNO low, while eosinophilic exacerbations can be differentiated by high FENO.