Lebrikizumab monotherapy effective in moderate to severe atopic eczema

28th March 2023

Lebrikizumab monotherapy given every two weeks without the use of topical steroids is effective for moderate to severe atopic eczema

Two identical randomised, double-blind, placebo-controlled trials have shown that treatment with lebrikizumab alone in patients 12 years of age and older with moderate to severe atopic eczema led to a significant improvement in disease severity.

Although atopic eczema affects approximately 20% of children, the condition persists in around 7% of adults. Moreover, atopic eczema has a huge negative impact on the quality of life of sufferers and can even increase the risk of suicide ideation.

While it has been recognised in recent years that elevated levels of both interleukin-4 and interleukin-13 (IL-13) are implicated in the pathophysiology of the disease, it has been recently demonstrated that IL-13 is the primary up-regulated cytokine in skin biopsy samples from patients with atopic eczema. The monoclonal antibody, lebrikizumab exerts selective antagonism of IL-13 and which is sufficient to control atopic eczema and improve patient’s quality of life.

In fact, a recent, randomised, phase 3 trial demonstrated the benefit of lebrikizumab when combined with topical steroids in adolescents and adults with moderate to severe atopic eczema. However, whether lebrikizumab is effective alone is currently unclear and was the objective of the current study.

The current publication includes the findings from two identical phase 3 trials, ADvocate1 and ADvocate2, in which patients with moderate-to-severe atopic eczema, aged 12 years and older, were randomised 2:1 to either lebrikizumab at a dose of 250 mg (loading dose of 500 mg at baseline and week 2) or placebo, administered subcutaneously every 2 weeks.

The primary outcome was based on an Investigator’s Global Assessment (IGA) score of 0 or 1 (indicating clear (0) or almost clear (1)), with a reduction of at least 2 points from baseline and was assessed after 16 weeks. The main secondary outcome was a 75% improvement in the Eczema Area and Severity Index score (EASI-75 response), whereas other measures included assessments of itch and of itch interference with sleep.

Lebrikizumab and atopic eczema disease severity

In the first trial, 424 patients with a mean age of 35.5 years (51.8% female) were randomised to lebrikizumab (283) or placebo with similar demographics in the second trial.

In the first trial, the primary outcome occurred in 43.1% of those assigned to lebrikizumab group and in 12.7% placebo patients and this difference was statistically significant (p < 0.001). In addition, a significant difference was seen in the EASI-75 response (58.8% vs 16.2%, p < 0.001). Similar and significant findings were observed in the second trial.

In both trials, a significantly higher proportion of patients given lebrikizumab group also achieved reductions in pruritus and improvements in sleep loss scores.

The authors concluded that 16 weeks of treatment with lebrikizumab was effective in adolescents and adults with moderate-to-severe atopic eczema.

Citation
Silverberg JI et al. Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis. N Eng J Med 2023.

Lebrikizumab and topical steroids effective in moderate to severe atopic eczema

19th January 2023

Lebrikizumab targets interleukin (IL)-13 and in combination with topical steroids appears effective in moderate to severe atopic eczema

Lebrikizumab in combination with low to mid-potency topical corticosteroids is an effective therapeutic approach for adults with moderate to severe atopic eczema according to the results of a randomised, placebo-controlled trial by an international research group.

Atopic eczema (AE) is a chronic, relapsing and remitting skin disease which, according to one UK-based study, affects up to 16.5% of children aged 2 years and 2.8% of adults aged 30-39. Moderate to severe disease symptoms include intense itch, sleep disturbance together with skin pain, affecting sleep, daily activities and occurs in 28.9% and 11% of adults, respectively. Both emollients and topical corticosteroids (topical steroids) are used to manage mild to moderate disease whereas systemic therapy and or phototherapy is recommended for those with more severe disease. In recent years, biologic therapies such as dupilumab have emerged for the treatment of individuals with moderate to severe disease.

Another recently introduced biologic is the monoclonal antibody lebrikizumab, which targets interleukin (IL)-13, a pro-inflammatory Th2 cytokine central to AE pathogenesis and which is an important driver of the clinical manifestations of AE. Although lebrikizumab has been shown to provide a rapid and dose-dependent efficacy across a broad range of clinical manifestations in adult patients with moderate to severe AE, no studies have examined the value of the drug in combination with topical steroids, which is reflective of real-life practice.

Consequently, in the current study, researchers randomised eligible patients, i.e., with a diagnosis of moderate-to-severe AE, 2:1 to lebrikizumab and topical steroids or placebo and topical steroids. An initial lebrikizumab loading dose of 500 mg was administered subcutaneously, at baseline and week 2, followed by 250 mg once every two weeks. The primary efficacy endpoint was the percentage of patients with an investigator’s Global Assessment scale (IGA) score of 0 or 1 (i.e., clear or almost clear) and a 2 or more point improvement from baseline at week 16. A key secondary objective was the percentage of patients achieving 75% improvement in EASI (EASI-75) at week 16.

Lebrikizumab and atopic eczema outcomes

A total of 211 patients with mean age of 37.2 years (48.8% female) were randomised to lebrikizumab and topical steroids (145) or placebo and steroids.

After 16 weeks of treatment, an IGA score of 0 or 1 with a 2-point or more reduction from baseline was achieved by 41.2% of those receiving lebrikizumab compared to 22.1% on placebo (p = 0.01), although a statistically significant difference was observed as early as week 8.

There was also a significantly higher proportion of lebrikizumab patients achieving an EASI75 (69.5% vs 42.2%, p < 0.01) and this time, a statistically significant difference was achieved and maintained from as early as week 4 and maintained through week 16.

The authors concluded on how lebrikizumab in combination with topical steroids was superior to topical steroids alone, adding how safety data was consistent with previously reported AE trials.

Citation
Simpson EL et al. Efficacy and Safety of Lebrikizumab in Combination With Topical Corticosteroids in Adolescents and Adults With Moderate-to-Severe Atopic DermatitisA Randomized Clinical Trial (ADhere). JAMA Dermatol 2023