ByRichard Gawel

Fact checked byKristen Dowd

April 24, 2024

4 min read

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Patients see fewer asthma exacerbations with lebrikizumab

ByRichard Gawel

Fact checked byKristen Dowd

Key takeaways:

Patients with baseline peripheral eosinophil counts of 300 cells/µL and higher had greater reductions in exacerbation rates.
FEV₁ totals improved with treatment compared with placebo as well.

Perspective from Sonali P. Majmudar, MD

Patients with asthma exacerbations and elevated blood eosinophils and fractional exhaled nitric oxide saw fewer exacerbations with lebrikizumab, according to a study published in the Journal of Allergy and Clinical Immunology: In Practice.

The safety profiles for adults and adolescents across the treatment groups were similar as well, Jonathan Corren, MD, associate clinical professor of medicine and pediatrics, David Geffen School of Medicine at UCLA, and colleagues wrote.

Reductions in adjusted exacerbation rates among adults at 52 weeks with lebrikizumab included 38% with a 125 mg dose and 41% with a 37.5% dose. — Data were derived from Corren J, et al. *J Allergy Clin Immunol* *Pract*. 2024;doi:10.1016/j.jaip.2024.02.007.

There were 976 adults in the LAVOLTA I study and 957 adults in the LAVOLTA II study who completed 52 weeks of treatment, along with 224 adolescents on placebo and 133 on lebrikizumab (Ebglyss, Lilly) who completed 52 weeks in the ACOUSTICS study.

LAVOLTA studies

The LAVOLTA studies included 495 exacerbations in their placebo groups, 365 among those patients treated with 125 mg of lebrikizumab and 334 among those treated with 37.5 mg doses.

Compared with placebo, the 125 mg groups in the LAVOLTA studies had a 29% reduction (adjusted RR = 0.71; 95% CI, 0.62-0.81) in their adjusted exacerbation rates (AERs), and the 37.5 mg group had a 35% reduction (aRR = 0.65; 95% CI, 0.57-0.75).

Specifically, among patients with baseline peripheral blood eosinophil counts of 300 cells/µL or higher and one or more exacerbations in the previous year, reductions improved to 38% for the 125 mg group (aRR = 0.62; 95% CI, 0.5-0.76) and 41% for the 37.5 mg group (aRR = 0.59; 95% CI, 0.48-0.73).

Patients with peripheral blood eosinophil counts of 300 cells/µL or higher and two or more exacerbations in the previous year saw even greater reductions, including 44% for those on 125 mg and 48% for those on 37.5 mg.

FEV₁ improved as well with lebrikizumab, including improvements of 0.09 L (95% CI, 0.05-0.13) among patients with 125 mg doses and 0.07 L (95% CI, 0.03-0.11) among those with 37.5 mg doses from baseline to week 52, compared with placebo.

Those patients with baseline peripheral blood eosinophils of 300 cells/µL or higher and one or more exacerbations in the previous year saw improvements of 0.15 L (95% CI, 0.07-0.24) among those on 125 mg and 0.13 L (95% CI, 0.04-0.21) among those on 37.5 mg, compared with placebo.

However, the researchers said that there were no significant differences in FEV₁ between the treatment and placebo groups among patients with baseline peripheral blood eosinophil counts of less than 150 cells/µL or between 150 cells/µL and 300 cells/µL and one or more exacerbations in the previous year.

Patients with mean fractional exhaled nitric oxide totals of 50 ppb or less and at least one exacerbation in the previous year experienced significant improvements in FEV₁ as well, the researchers said.

ACOUSTICS study

In ACOUSTICS, 51 of the placebo patients (98.4 patient-years of follow-up), 31 of the patients using 125 mg of lebrikizumab (105.1 patient-years) and 31 of those on 37.5 mg (100.8 patient-years) reported exacerbations.

Reductions in AERs included 51% for the patients (n = 116) on 125 mg doses (aRR = 0.49; 95% CI, 0.28-0.83) and 40% (aRR = 0.6; 95% CI, 0.35-1.03) for the patients (n = 113) on 37.5 mg doses.

Also in ACOUSTICS, reductions increased to 59% (aRR = 0.41; 95% CI, 0.19-0.88) for the group on 125 mg doses and 64% (aRR = 0.36; 95% CI, 0.15-0.87) for those on 37.5 mg doses among those patients with baseline peripheral blood eosinophil counts of 300 cells/µL and higher with one or more exacerbations in the previous year.

Patients also experienced improvements in prebronchodilator FEV₁ with placebo-corrected mean changes of 0.2 L (95% CI, 0.05-0.34) for the 37.5 mg group and 0.05 L (95% CI, –0.09 to 0.2) for the 125 mg group from baseline to week 52.

These improvements increased to 0.25 L (95% CI, –0.01 to 0.51) for those on 125 mg and 0.33 L (95% CI, 0.06-0.6) for those on 37.5 mg among patients with baseline peripheral blood eosinophil counts of 300 cells/µL or higher and one or more exacerbations in the previous year.

Pooled safety findings

A pooled analysis of all three studies found that 77% of those patients on lebrikizumab and 78% of those on placebo experienced treatment-emergent adverse events, including 20.5% of the treatment group and 18.8% of the placebo group reporting nonserious and mild events and 48.8% of the treatment group and 50.4% of the placebo group reporting moderate events.

The most frequent treatment-emergent adverse events included asthma (30.6% with lebrikizumab, 37.6% with placebo), nasopharyngitis (13.2% with lebrikizumab, 14.2% with placebo), and upper respiratory tract infections (11.5% with lebrikizumab, 9.1% with placebo).

Also, 3.4% of the treatment group (n = 56) and 3.6% of the placebo group (n = 30) dropped out of the study due to adverse events, which the researchers called similar. Rates of serious adverse events, including 7.6% for the treatment group and 8.5% for the placebo group, were similar as well, the researchers said.

None of the patients in the placebo group and 1.1% of the patients in the treatment group reported eosinophilia treatment-emergent adverse events. Also, 0.2% of the patients in each group reported eosinophil-related disorders.

At any point after baseline, 37.6% of the treatment group and 22% of the placebo groups had increased eosinophils, with most shifts moving from normal (< 500 cells/µL) to mild (500 cells/µL to < 1,500 cells/µL) counts and 0.2% moving to severe counts ( 5,000 cells/µL).

These findings indicate the importance of using appropriate predictive biomarkers when selecting specific biologic medications for patients with asthma, noting the safety and effectiveness of lebrikizumab for patients with moderate to severe, poorly controlled eosinophilic asthma in this study.

Perspective

Sonali P. Majmudar, MD

This is an interesting study that highlights an opportunity for better asthma control in adult and pediatric patients with severe eosinophilic asthma. It is well-known that IL-13 is one of the cytokines involved with the T2 pathogenesis of asthma, and this study suggests that targeted IL-13 inhibition can reduce the severity of such exacerbations. These results are exciting, as currently there are no specific guidelines for the management of asthma in patients with blood eosinophil levels of 300 cells/µL or greater. However, the results must be interpreted in the context of a few limitations as a post-hoc analysis, which the authors describe. Further study is warranted to validate the study results and determine long-term efficacy.

Sonali P. Majmudar, MD

Allergist and Immunologist, Hoffman Estates and Algonquin, Illinois

Disclosures: Majmudar reports no relevant financial disclosures.

Sources/Disclosures

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Source:

Corren J, et al. J Allergy Clin Immunol Pract. 2024;doi:10.1016/j.jaip.2024.02.007.

Disclosures: Corren reports having financial relationships with Amgen, AstraZeneca, Eli Lilly and Company, Genentech, Novartis, Optinose, Regeneron and Sanofi. Please see the study for all other authors’ relevant financial disclosures. The study was funded by F. Hoffmann-La Roche Ltd. Post hoc statistical analyses were funded by Dermira. Eli Lilly and Company provided additional funding for statistical analyses.

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