Lebrikizumab Provides Lasting Relief for Itch and Sleep in Atopic Dermatitis

Lebrikizumab shows promise in delivering sustained relief for patients with atopic dermatitis, as recent findings reveal steady improvements in itch and sleep loss from Week 16 through Week 52.¹

Placebo-controlled trials have demonstrated lebrikizumab significantly improves skin clearance measures and patient-reported outcomes by Week 16 for patients with moderate-to-severe atopic dermatitis. Despite the positive evidence, the US Food and Drug Administration (FDA) issued a complete response letter (CRL) for lebrikizumab’s biologic license application (BLA) for the treatment of atopic dermatitis, announced by Eli Lilly and Company on October 2, 2023.²

Since then, Eli Lilly and Company announced on April 30, 2024, that they resubmitted lebrikizumab to the FDA for the treatment of adult and adolescent patients with atopic dermatitis.³ With the FDA’s decision on the application still pending, investigators, led by Gil Yosipovitch, from the University of Miami Miller School of Medicine, conducted another study to better assess lebrikizumab.1 Investigators sought to evaluate the sustained impact of lebrikizumab monotherapy up to 52 weeks and between visits on the frequency of itch and sleep loss symptoms in patients with moderate-to-severe atopic dermatitis.

“What we really wanted to understand is during the maintenance phase of treatment in the clinical trials, did individuals have a stable response to itch and sleep? Was this something that actually was staying the same over time? Was it getting worse? Was it getting better? And that was really the crux of the analysis,” investigator Raj Chovatiya, MD, PhD, from the Chicago Medical School at Rosalind Franklin University of Medicine and Science, told HCPLive.

Investigators studied the sustained impact of lebrikizumab in 2 phase 3 studies: ADvocate1 and ADvocate2. Both were identically designed 52-week randomized, double-blind, parallel-group, placebo-controlled, monotherapy trials with participants ≥ 12 years who weighed ≥ 40 kg and had moderate-to-severe atopic dermatitis that met the Eczema Area and Severity Index Score of ≥ 16, an Investigator’s Global Assessment (IGA) score of ≥ 3, and a body surface area (BSA) involvement of ≥ 10%. Participants had chronic atopic dermatitis for > 1 year and did not receive adequate relief on topical treatment to control symptoms.

Participants were randomized 2:1 to receive lebrikizumab 250 mg every 2 weeks, every 4 weeks, or placebo by subcutaneous injection for 36 weeks. The analysis looked at participants who achieved a Patient-Oriented Eczema Measure (POEM) response of 0 (no days with symptoms) or 1 (1 – 2 days with symptoms) for itch and sleep disturbance. The reported results excluded data from patients who discontinued treatment, used rescue medications, or were transferred to an escape treatment arm.

Ultimately, the findings reveal lebrikizumab effectively improved itch and sleep disturbance over the study period. At Week 16, 35.9% and 39.3% of participants who took lebrikizumab every 2 and 4 weeks, respectively, responded 0 or 1 to the itch item of POEM. Moreover, 12.6% and 12.1% who took lebrikizumab every 2 weeks or every 4 weeks, respectively, responded had no days with itch symptoms.

Additionally, 66% and 72.6% of participants, respectively, responded 0 or 1 to the Sleep Disturbances item of POEM. In total 37.9% and 44.3%, respectively, responded 0 to the Sleep Disturbances item.

By Week 52, 44.4% and 48% of participants who took lebrikizumab every 2 and 4 weeks, respectively, responded 0 or 1 to the Itch item; 21.5% and 18.7% of patients, respectively, responded 0. As for the sleep item of POEM, 83.1% and 78.4% responded 0 or 1, respectively; 67.7% and 59.5% responded 0, respectively.

“…there wasn't a heavy degree of fluctuation in terms of people dropping in and out, of doing well,” Chovatiya said. “If anything, for the folks that really made their way through the trial and stayed in, it was very consistent. What this tells us is that in the early phase, after a few months of treatment, if you're doing pretty well, odds are that's going to be a very stable response, and that this doesn't extend only to what the skin looks like, but also the itch and sleep, which we know are oftentimes the major burden that our patients face.”

References

1. ^{Yosipovitch G, Lio P, Legat FJ, et al. Stable Response and Sustained Improvement of Itch and Sleep Symptoms in Patients with Atopic Dermatitis Treated with Lebrikizumab over 52 Weeks. Dermatol Ther (Heidelb). Published online July 13, 2024. doi:10.1007/s13555-024-01225-w}
2. ^{Smith, T. FDA Issues Complete Response Letter for Lebrikizumab Treatment of Eczema. HCPLive. October 2, 2023. https://www.hcplive.com/view/fda-issues-complete-response-letter-lebrikizumab-treatment-eczema. Accessed August 15, 2024.}
3. ^{Smith, T. Lebrikizumab for Atopic Dermatitis Resubmitted for FDA Approval After Previous Rejection. HCPLive. April 30, 2024. https://www.hcplive.com/view/lebrikizumab-for-atopic-dermatitis-resubmitted-for-fda-approval-after-previous-rejection. Accessed August 15, 2024.}