Patients with small airways disease have poor response to biologic therapy for asthma

Key takeaways:

• Response was defined as suspension of systemic corticosteroids and fewer than two flare-ups after treatment.
• More than 50% of patients who did not respond to biologic treatment had small airways disease.

Patients with severe asthma and small airways disease did not respond as well to omalizumab treatment, according to a poster presented at the European Respiratory Society International Congress.

“Small airways disease is common in pediatric and adult asthma, particularly in those with more severe disease or more frequent symptoms,” Martina Maria Marinato, severe asthma unit, Careggi University Hospital, Florence, Italy, said during her presentation.

“The assessment and monitoring of small airways disease in severe asthma is limited by the relative inaccessibility of this region of the lung and for the lack of a gold standard,” she continued.

Noting that few studies have correlated the involvement of small airways in severe asthma with response to biologic therapies, Marinato said that she and her colleagues set out to determine the prevalence of small airways disease and predict response to biologics among 160 outpatients referred to their unit.

The cohort included 60 patients on omalizumab (Xolair; Genentech, Novartis), 23 on benralizumab (Fasenra, AstraZeneca), 32 on mepolizumab (Nucala, GSK) and 41 on dupilumab (Dupixent; Regeneron, Sanofi).

The researchers defined response to biologics as complete suspension of systemic corticosteroids and fewer than two asthma flare-ups within the year following the beginning of treatment.

Also, the researchers defined small airways disease as altered spirometry including residual volume higher than 120% and forced expiratory flow between 25% and 75% of less than 65%, along with forced oscillometry technique results of resistance between 5 Hz and 20 Hz greater than 0.03 kPa/L/s (R5-R20 < 0.03 kPa/L/s) or reactance at 5 Hz less than the lower limit of normality (X5 [%] < LLN).

Spirometry found that 37% of responders and 70% of nonresponders had R5-R20 of less than 0.03 kPa/L/s, with a Fisher Exact test result of 0.002. Also, 20% of responders and 60% of nonresponders had X5 (%) of less than the LLN, with a Fisher Exact test of less than 0.001. Overall, 38.8% of responders and 66.7% of nonresponders (Fisher Exact test = 0.008) were considered to have small airways disease.

Compared with responders, nonresponders had greater prevalence of small airway disease, surpassing 50%, the researchers said.

Specifically, patients with X5 (%) less than LLN included 4% of the benralizumab group, 45% of the dupilumab group, 22% of the mepolizumab group and 28% of the omalizumab group, with a Fisher-Freeman-Halton exact test result of 0.004.

“Logistic regression analysis shows that reactance at 5 Hz less than the lower limit of normality is a negative predictive variable of response to biological therapy,” Marinato said.

Patients with R5-R20 greater than 0.03 kPa/L/s included 43% of the benralizumab group, 55% of the dupilumab group, 53% of the mepolizumab group and 33% of the omalizumab group.

“After 1 year of treatment, the patients on omalizumab showed significantly impaired lung function and lower response to therapy,” Marinato said.

As predictors of response to biologic treatment, small airways disease had a P value of .007 and altered forced oscillometry technique had a P value of .004.

“The small airways disease phenotype, particularly characterized by the reactants at 5 Hz less than the lower limit of normality, is associated with lower response to biological therapy,” Marinato said.