Lebrikizumab

Lebrikizumab is a high-affinity monoclonal antibody that selectively binds to soluble interleukin-13 (IL-13). It thereby prevents the formation of the heterodimer complex IL-13Rα1/IL-4Rα, and thus the subsequent signal transmission. IL-13 is significantly involved in the development of atopic dermatitis, as it promotes the underlying type 2 inflammation, which leads to a dysfunction of the skin barrier as well as itching, skin thickening and infections.

In two randomized, placebo-controlled, double-blind Phase III studies, children (≥ 12 years), adolescents and adult patients with moderate to severe AD were randomly treated with placebo or with subcutaneous injections of lebrikizumab (250 mg every 2 weeks (500 mg at baseline and week 2) (Silverberg JI et al. 2023). Compared to placebo, complete or near-complete resolution of skin disease was observed in 43% and 33% in the lebrikizumab groups after 16 weeks compared to 13% and 11%, respectively. The proportion of patients with a 75% improvement in EASI score (EASI 75) was 59% and 52% in the treatment groups and 16% versus 18% in the placebo groups. Itching and sleep disturbances were also significantly improved with treatment. Conjunctivitis was described as an adverse effect.

Lebrikizumab is indicated and approved for the treatment of moderate to severe atopic dermatitis in adults and adolescents aged 12 years and over weighing at least 40 kg who are eligible for systemic therapy.

Acute relapse, short-term, long-term treatment In phase II studies with lebrikizumab, a dosage of 500 mg at the beginning and after week 2 and then every 2 weeks of 250 mg proved to be optimal. An approved dosage is not yet available at the time of finalization of the guideline. Safety Treatment-related adverse events were observed in over 45% of patients in the treatment groups and over 51% in the placebo groups in the phase III studies; most were mild to moderate and did not lead to discontinuation of treatment.

Combination with other therapies: The use of topical steroids during the onset of AD relapses in combination with lebrikizumab may be appropriate, as biologics as monotherapy have previously been reported to result in high dropout rates and presumed failure rates in patients.

The antibody was well tolerated overall. The majority of adverse events in the studies were mild or moderate and did not lead to discontinuation of treatment. The most common adverse events were (allergic) conjunctivitis, injection site reactions and dry eye (Silverberg JI et al. 2023).

Preparation ^Ebglyss® (Almirall)

The positive vote of the EMA's Committee for Medicinal Products for Human Use is based on the Phase III studies ADvocate 1 and ADvocate 2, in which lebrikizumab was investigated as monotherapy, and on the Phase III study ADhere, in which lebrikizumab was tested in combination with topical corticosteroids in adult and adolescent patients with moderate to severe atopic dermatitis.

1. Blauvelt A et al. (2023) Efficacy and safety of lebrikizumab in moderate-to-severe atopic dermatitis: 52-week results of two randomized double-blinded placebo-controlled phase III trials. Br J Dermatol. 188: 740-748.
2. Silverberg JI et al. (2023) Two Phase 3 Trials of Lebrikizumab for Moderate-toSevere Atopic Dermatitis. N Engl J Med 388:1080-1091.