Mepolizumab ‘super responders’ seen in severe eosinophilic asthma

Real world patients with severe eosinophilic asthma show the same good outcomes with mepolizumab as seen in clinical trials – with a particular group of ‘super responders’ with a T2 phenotype, an Australian study has shown.

A registry based study found that the anti-IL5 treatment reduced severe exacerbations, hospitalisations and improved asthma symptoms, quality of life and lung function in patients with severe eosinophilic asthma.

Researchers at the Hunter Medical Research Institute, NSW , reviewed outcomes for 309 patients with severe eosinophilic asthma were enrolled in the Australian Mepolizumab Registry (AMR).

Prior to starting mepolizumab the patients (median age 60 years, 58% female) had poor symptom control, with a median Asthma Control Questionnaire (ACQ)-5 score of 3.4. Despite taking an average of four asthma medications, they had frequent exacerbations that required three courses of oral corticosteroids  in the previous year.

After starting mepolizumab, blood eosinophil levels reduced from a median of 590 cells/μL to 100 within three months, and remained at this level at 12 months

At 12 months, patients receiving mepolizumab had significantly reduced severe exacerbations requiring oral steroids by 66% compared to the previous year (annualised rate ratio 0.34). Hospitalisations were reduced by 54% (rate ratio 0.46).

Significant improvements were also seen in asthma symptom control (ACQ-5 reduced by 2.0 at 6 months), quality of life and lung function after taking mepolizumab.

The proportion of patients requiring maintenance oral steroids was reduced from 47% at baseline to 30% at the 6-month assessment (p<0.001), and the daily steroid dose reduced from median 10 to 7.5mg/day prednisolone equivalent.

Better response (ACQ-5 score) to mepolizumab treatment was predicted by higher blood eosinophil levels, whereas being male or being obese (BMI ≥30) predicted a lesser response.

Clinical responses to mepolizumab were similar in both the early and late age of asthma onset.

Overall, 86% of patients were responders and 31% achieved very well-controlled symptoms (ACQ-5<1.0). A group of ‘super-responders’ were recognised as having an exceptionally good response to mepolizumab, in the top 25% of ACQ responses (61 of 252 responders). They were predominantly female, had a lower BMI and tended to be non-smokers.

Importantly, super responders had high levels of T2 disease expression as indicated by higher baseline blood eosinophils (median 700 vs 535 cells/μL) and FeNO (41vs 23) and a higher baseline ACQ-5 (median 4.2 vs 3.0) compared to poor responders.

The study investigators – including Professor Peter Gibson – said the registry data show that when targeted via PBS criteria the treatment effect of mepolizumab in real world patients is as great, if not greater, than that reported in RCTs, despite the population having more severe asthma, being older, and having a greater comorbidity profile.

And the ability to identify ‘super-responders’ will be useful because individual patients with severe asthma may be eligible for several different add-on treatment options, they said.

“Mepolizumab super-responders had shorter duration of asthma, less severe disease and had substantial treatment response. As such, appropriate patient phenotyping and targeting with mepolizumab therapy at an early time-point during the progression of disease, for example as soon as asthma is identified as severe, may be advantageous in this context,” they wrote.

The findings are published in the European Respiratory Journal.

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