Lebrikizumab combined with topical corticosteroids (TCS) delivers rapid, clinically significant improvements that can be maintained for a full year in adults and adolescents with moderate-to-severe atopic dermatitis who have failed or are unsuitable for ciclosporin A, according to results of a recent phase 3 trial.
Ciclosporin A remains the only conventional systemic therapy approved across much of Europe for severe atopic dermatitis, but its use is limited by toxicity and suboptimal long-term efficacy.
Lebrikizumab, a selective interleukin-13 monoclonal antibody, has previously demonstrated robust efficacy and a favourable safety profile in broader atopic dermatitis populations.
The recent ADvantage trial, led by researchers at the University of Manchester, UK, evaluated lebrikizumab in patients with chronic moderate-to-severe atopic dermatitis for whom ciclosporin A was ineffective, intolerable or contraindicated.
Safety and efficacy of lebrikizumab plus TCS
A total of 331 patients aged 12 years and older from nine European countries were randomised 2:1 to receive lebrikizumab 250 mg every two weeks plus TCS, or placebo plus TCS, during a 16-week induction period. All participants then entered a 36-week open-label maintenance phase on lebrikizumab.
Baseline disease burden was substantial, with a mean Eczema Area and Severity Index (EASI) score of 28, and 39% classified as severe by Investigator’s Global Assessment (IGA). More than half of participants had previously received ciclosporin A.
At week 16, the primary endpoint of EASI-75 was achieved by 68.4% of patients receiving lebrikizumab plus TCS, compared with 40.8% in the placebo plus TCS group (p<0.001). Higher response rates were also seen for EASI-90, IGA 0/1 and clinically meaningful reductions in pruritus.
Benefits emerged as early as Week 4 for some endpoints and continued to build during maintenance. By Week 52, 88.9% of patients had achieved EASI-75, while 71.7% achieved EASI-90 and 64.4% reached IGA 0/1. Significant improvements in health-related quality of life were also reported.
The use of low- or mid-potency TCS declined over time, with fewer than half of patients still using permitted TCS by Week 52. Rates of rescue therapy remained low throughout the study. Safety findings were consistent with the established profile of lebrikizumab.
During the induction phase, treatment-emergent adverse events occurred in 62.3% of patients receiving lebrikizumab versus 53.2% in the placebo group, with most events described as mild or moderate. Serious adverse events and treatment discontinuations were infrequent.
Limitations and future directions
The researchers noted that inadequate response to prior ciclosporin A treatment was defined by investigator judgement rather than standardised criteria. Secondary outcomes were not adjusted for multiplicity, and the dosing regimen used – every two weeks for 52 weeks – differed from real-world guidance, which permits four-weekly maintenance dosing after Week 24.
Overall, the investigators conclude that lebrikizumab combined with TCS represents an effective and well-tolerated targeted treatment option for this challenging patient population, with sustained benefits maintained over 52 weeks.
They added that further research will be important to determine optimal long-term dosing strategies.
Reference
Warren RB et al. Efficacy and safety of lebrikizumab in adult and adolescent patients with moderate-to-severe atopic dermatitis inadequately controlled with or ineligible for ciclosporin A: a placebo-controlled, randomized phase IIIb clinical study (ADvantage). Br J Dermatol 2025;193:876-88.
This article was originally published by our sister publication Hospital Healthcare Europe.
