Biomarkers that predict ICS, LAMA response may differ in adults vs adolescents with asthma
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Biomarkers that predict response to inhaled corticosteroid or long-acting muscarinic antagonist treatment may differ between adults and adolescents with uncontrolled mild persistent asthma, researchers reported.
“In the combined study population of adults and adolescents enrolled in the SIENA trial, we previously reported that blood eosinophil levels and the fractional exhaled nitric oxide each predicted response to inhaled corticosteroids for the composite outcome but not response to LAMA,” Jerry A. Krishnan, MD, PhD, associate vice chancellor for population health sciences and professor of medicine and public health at the University of Illinois, Chicago, and colleagues wrote in Annals of the American Thoracic Society. “In the current report, we present the results of prespecified exploratory analyses of the predictive value of various type 2 inflammatory and physiological biomarkers on the response to inhaled corticosteroids or LAMA separately in adolescents and adults enrolled in the SIENA trial.”
Among the 295 participants in the randomized SIENA trial, about 20% of adults and 40% of adolescents required acute care for one or more asthma episodes in the previous year.
Krishnan and colleagues aimed to identify biomarkers of treatment response after 12 weeks of treatment with an inhaled corticosteroid (ICS; mometasone; Asmanex, Merck), LAMA (tiotropium; Spiriva, Boehringer Ingelheim) or placebo in adults and adolescents.
The primary outcome was asthma control, which was defined as a composite of treatment failure, asthma control days and FEV1.
Sputum, blood eosinophil levels and fractional exhaled nitric oxide were each predictive of ICS response in 237 adults, with areas under the curve of 0.61, 0.64 and 0.62, respectively (P < .01 for all). For blood eosinophil levels and fractional exhaled nitric oxide together, the AUC was 0.66 (P < .001), according to the results.
Number of positive aeroallergens and total serum immunoglobulin E each predicted ICS response in 58 adolescents, with an AUC of 0.69 and 0.73, respectively (P < .03 for both). For number of positive allergens and total serum immunoglobulin E together, the AUC was 0.73 (P = .003), according to the results.
In addition, FEV1 reversibility predicted LAMA response in adults but not in adolescents after ipratropium bromide, with an AUC of 0.61 (P = .007).
“Although the AUCs for the T2 inflammatory and physiological biomarkers we examined were not high enough to confidently identify individuals with asthma who respond to ICS and LAMA, our findings indicate that the biomarkers that predict response to ICS (or LAMA) therapy are likely to be different in adults versus adolescents. Type 2 inflammatory and physiology biomarker-stratified clinical trials are needed to identify ICS or LAMA as first-line controllers specific to adults and adolescents with mild persistent asthma,” the researchers wrote.