Asthma

Ambitious research program targets steroid non-responsive asthma


A new study in the United Kingdom will explore the use of biomarkers to identify patients with severe asthma who are non-responsive to corticosteroids and might benefit from novel treatment approaches.

Professor Liam Heaney, from Queen’s University of Belfast, and colleagues say the existing ‘one size fits all’ model of stratifying asthma is inadequate, being based on the level of disease control and the response to stepwise increases in corticosteroids.

About half of asthma patients have typical eosinophilic airway inflammation driven by type 2 cytokines (‘T2-high’ asthma) which responds well to corticosteroids.

In the remainder, with ‘T2-low’ disease, corticosteroids have little or no effect.

The project, dubbed the MRC UK Refractory Asthma Stratification Programme (RASP-UK), will aim to define three groups:

  • patients who do not adhere with corticosteroid therapy
  • those with persistent inflammation and eosinophilia despite high-dose inhaled steroids who often require systemic steroids and may benefit from the range of biological therapies targeting T2-high disease soon to become available
  • those who are non-responsive to steroids and most likely have T2-low disease, for whom there are currently few treatment options.

“These [steroid non-responsive] patients represent a significant unmet medical need where new targets need to be identified so drugs can be developed,” Professor Heaney wrote in Thorax.

Only 25-50% of patients with severe asthma have prototypic high-T2 gene signatures.

“In many cases it seems likely that the corticosteroid dose has been escalated inappropriately to try and manage persistent symptoms that are not corticosteroid responsive,” he says.

The study will use a composite biomarker score incorporating fractional exhaled nitric oxide (FeNO), blood eosinophils and periostin.

The score accurately predicted exacerbation risk in the placebo arms of omalizumab and lebrikizumab clinical trials.

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