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Letter
Mepolizumab in refractory eosinophilic asthma
  1. I D Pavord1,
  2. P Haldar1,
  3. P Bradding2,
  4. A J Wardlaw2
  1. 1Institute for Lung Health, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, UK
  2. 2University of Leicester, Leicester, UK
  1. Correspondence to Professor I D Pavord, Institute for Lung Health, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester LE3 9QP, UK; ian.pavord{at}uhl-tr.nhs.uk

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In a recent Lung Alert reviewing our study of mepolizumab in severe eosinophilic asthma,1 Barratt states that the study population represented a minority of patients with asthma and that they had corticosteroid-resistant disease.2 These comments require clarification. While we accept that the population studied by us represents about 3% of the total asthma population, it was 30% of patients with refractory asthma, a population with the greatest unmet need for new treatment. In contrast, only 13% of this population meet criteria set out by the manufacturer for treatment with omalizumab, and only a minority of these meet NICE criteria for use of the agent.

Our patients were corticosteroid resistant in the sense that they continued to have morbidity despite high-dose inhaled corticosteroids and, in many cases, oral prednisolone. However, many responded well to higher-dose oral prednisone, and a post hoc analysis showed that those who did tended to do better with mepolizumab treatment (table 1). In contrast, there was a poorer response to mepolizumab in patients with marked bronchodilator reversibility. The clear implication is that mepolizimab works best in patients who have airflow limitation and symptoms as a result of corticosteroid-responsive airway inflammation rather than airway smooth muscle contraction. Interestingly, the exact opposite relationship between acute bronchodilator response and clinical efficacy has recently been reported for treatment with anti-tumour necrosis factor α,3 a treatment which targets airway smooth muscle function but not eosinophilic airway inflammation.4 It therefore appears that the population that does well with these different anti-cytokine strategies can be recognised by identifying the mechanism of airflow limitation.

Table 1

Exacerbation numbers by tertile of response to prednisolone and salbutamol

We believe that clinicians who see large numbers of patients with inflammatory airway diseases will readily recognise patients with prednisolone-responsive bronchodilator-resistant airflow limitation and/or symptoms in their asthma, cough and COPD clinics. The challenge is that many of these patients have disease that is difficult to classify using current physiology-based classification systems. The optimum development of mepolizumab and other promising agents does require new and better ways of assessing and classifying inflammatory airways disease.

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Footnotes

  • Competing interests None.

  • Provenance and peer review Not commissioned; not externally peer reviewed.

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