Biomarker-based adjustment fails to reduce asthma corticosteroid dose

A composite type-2 biomarker corticosteroid adjustment strategy did not result in a greater proportion of patients with severe asthma reducing their corticosteroid dose, according to results published in The Lancet Respiratory Medicine.

“A biomarker-adjusted corticosteroid strategy seems particularly beneficial in those patients where symptoms and type-2 biomarker profile are discordant and, as seen in up to 50% of patients with severe asthma,” Liam G. Heaney, MD, clinical professor at the Center for Experimental Medicine in the School of Medicine, Dentistry and Biomedical Sciences at Queen’s University, Belfast, U.K., and colleagues wrote. “We suggest that before progression to high-dose inhaled and systemic corticosteroid treatment, predictive biomarkers of therapeutic response should be assessed.”

Researchers conducted a randomized, controlled, single-blind, parallel-group trial in 301 patients with severe asthma and fractional exhaled nitric oxide less than 45 parts per billion from 2016 to July 2018. Patients were randomly assigned by an online electronic case-report form stratified by asthma control and rescue systemic steroid use to the biomarker group (n = 240) or a control group (n = 61) in the intention-to-treat population. A per-protocol population (n = 121) was included in this study for analysis.

Patients attended clinic every 8 weeks and their treatment was adjusted following automated treatment-group-specific algorithms, according to the researchers. Patients in the biomarker group received an advisory to maintain treatment, and patients in the control group had their treatment adjusted according to the algorithm.

Primary outcome was number of patients with corticosteroid dose reduction at 48 weeks in the intention-to-treat population. Secondary outcomes included inhaled corticosteroid dose at the study conclusion and cumulative dose during the study, number of patients on maintenance oral corticosteroids at the study conclusion, rate of annual severe asthma exacerbations, time to first severe exacerbation, number of asthma hospital admissions, lung function changes, Asthma Control Questionnaire-7 score, Asthma Quality of Life Questionnaire score and type-2 biomarkers from baseline to 48 weeks.

At week 48, 28.4% of patients in the biomarker group were receiving a lower corticosteroid dose compared with 18.5% of patients in the control group (adjusted OR = 1.71; 95% CI, 0.8-3.63; P = .17), according to the results. A greater proportion of patients in the per-protocol population were receiving a lower corticosteroid dose at 48 weeks in the biomarker group (30.7% vs. 5%; aOR = 11.48; 95% CI, 1.35-97.83; P = .026).

Researchers observed no difference in secondary outcomes between both groups and no loss of asthma control among those in the biomarker group who reduced corticosteroid dose. Patient choice to not follow treatment advice was cited as the main reason for loss to per-protocol analysis.

“We noted a large number of patients who did not follow treatment advisories to reduce corticosteroid treatment in both treatment groups,” the researchers wrote. “Understanding the reasons for this finding is an important area for future research.”