A group of international experts has reached a consensus on the clinical definition of super-responders (SR) to severe asthma treatment, paving the way to a better understanding of the phenomenon as well as asthma pathophysiology and phenotypes.
The research behind the definition, published in The Journal of Allergy and Clinical Immunology: In Practice, is based on a survey of 81 international severe asthma experts from 24 countries.
The team used a modified Delphi process consisting of three iterative rounds in which statements and questions regarding response criteria were sent to panel members for ranking on a five-point scale (strongly agree, agree, neutral, disagree, and strongly disagree), with a cutoff of 70% for agreement.
The final consensus definition for severe asthma super-responder requires three criteria to be met, two of which must be major, i.e exacerbation elimination, major improvement in asthma control, or cessation of maintenance oral corticosteroids (or weaning to adrenal insufficiency).
Minor criteria were defined as a 75% reduction in exacerbations over 12 months, well-controlled asthma and an at least 500ML improvement in FEV1.
The panel stressed that clinical improvement should be observed over 12 months, and that no criteria in the same domain should be double counted (e.g. if exacerbation elimination was achieved a 75% exacerbation reduction as an additional minor criterion should not be included).
“This international consensus-based definition of severe asthma SRs is an important prerequisite for better understanding SR prevalence, predictive factors, and the mechanisms involved,” the authors said. “Further research is needed to understand the patient’s perspective and to measure quality of life more precisely in SRs.”
In an accompanying editorial, Drs Hitasha Rupani, Consultant Respiratory Physician at University Hospital Southampton NHS Foundation Trust, UK, and Mark Hew, Head of Allergy, Asthma & Clinical Immunology service at Alfred Health in Melbourne, Australia, said the super-responder definition “is an important step toward marking asthma remission possible for all patients with asthma”.
“Precise characterisation of super-responder populations to individual therapies, or classes of therapies, should help clinicians choose between targeted therapies for patients, and get it right first time,” while “identifying super-responder characteristics may yield new mechanistic insights regarding the mode of action of targeted therapies, with potential for new drug discovery,” they said.
“The super-responder definition represents a fresh metric for therapeutic outcomes and provides a tangible way to raise the therapeutic bar in severe disease, from asthma control to the far more ambitious paradigm of asthma remission”.