Lebrikizumab reduces asthma exacerbation in adolescents

Treatment with either high- or low-dose lebrikizumab reduces the rate of exacerbation in patients with uncontrolled asthma, according to the ACOUSTICS* trial presented at ATS 2022.

This phase III, double-blind, placebo-controlled trial involved 346 adolescent patients (aged 12–17 years) with uncontrolled asthma despite previous treatment with daily inhaled corticosteroid and ≥1 use of a second asthma controller medication. Participants were randomized to receive lebrikizumab 125 mg (high dose; n=116) or 37.5 mg (low dose; n=113) every 4 weeks or placebo (n=117) for 52 weeks. The primary endpoint of the study was the rate of asthma exacerbation, defined as new or worsened asthma symptoms that led to treatment with systemic corticosteroids or hospitalization. [ATS 2022, abstract 8247]

Of the 224 participants who completed the 52-week treatment period, only 58.0 percent had received the full 13 doses of lebrikizumab.

At week 52, patients treated with either high- or low-dose lebrikizumab achieved 51.0 percent (rate ratio [RR], 0.49) and 40.0 percent (RR, 0.60) reduction, respectively, in the rate of asthma exacerbation compared with placebo.

Among patients with a blood eosinophil count of ≥300 cells/µL at baseline, those who received lebrikizumab had a remarkable reduction in asthma exacerbation rates by 56.0 percent in the high-dose arm (RR, 0.44) and 58.0 percent in the low-dose arm (RR, 0.42) compared with those in the placebo arm.

“Despite the lack of a consistent dose-response in the ACOUSTICS study data, … [previous studies have shown that lebrikizumab-treated] adults with uncontrolled asthma … with prior exacerbations and blood eosinophil counts [of] ≥300 cells/µL had greater reductions in asthma exacerbation rate … compared with placebo,” said lead author Dr Stanley Szefler from the Department of Pediatrics at Children’s Hospital Colorado and University of Colorado School of Medicine in Aurora, Colorado, US.

Similar rates of treatment-emergent adverse events (TEAEs) were observed across all treatment groups (68.1 percent and 67.3 percent for high- and low-dose lebrikizumab, respectively, and 61.5 percent for placebo). All AEs were mostly considered mild to moderate in severity and did not lead to treatment discontinuation.

“Treatment with lebrikizumab reduced the exacerbation rates in adolescent patients, [with a] greater effect observed with the 125-mg dose than with the 37.5-mg dose in the overall population,” said Szefler.

“[In addition, the] exacerbation rates were trending toward further reduction in [lebrikizumab-treated] patients who have baseline blood eosinophilia,” Szefler added.

This is the largest cohort of adolescents with asthma, Szefler said; however, the study was prematurely terminated by the sponsor, and this might have limited the interpretation of results. Nonetheless, the findings still showed a safety profile in the adolescent population consistent with that previously observed with lebrikizumab in the adult population, he noted.

*ACOUSTICS: A study of lebrikizumab in adolescent participants with uncontrolled asthma who are on inhaled corticosteroids and a second controller medication