Lebrikizumab for atopic dermatitis

Background:
Atopic dermatitis is a chronic, relapsing inflammatory skin disease characterised by pruritus and eczematous lesions. It is most common in children but can affect people of all ages. Management requires a combination of nondrug treatment (e.g. avoidance of triggers, moisturisers) and drug therapy (mainly intermittent topical corticosteroids). Moderate to severe atopic dermatitis can be treated systemically with immunosuppressant drugs (e.g. ciclosporin), Janus kinase (JAK) inhibitors (e.g. baricitinib, upadacitinib) or monoclonal antibodies (e.g. dupilumab).¹

Lebrikizumab is a new monoclonal antibody developed for the treatment of atopic dermatitis in adults and adolescents whose symptoms are not adequately controlled by topical therapies.²

Mechanism of action:
Lebrikizumab is a recombinant humanised IgG4 monoclonal antibody that selectively binds to interleukin-13 (IL-13), a key cytokine involved in the pathogenesis of atopic dermatitis. By inhibiting IL-13 signalling, lebrikizumab reduces inflammation, skin barrier dysfunction and pruritus.²

Clinical trials:
Lebrikizumab was approved based on three pivotal phase 3 randomised controlled trials – ADvocate1, ADvocate2 and ADhere – which all enrolled patients aged 12 years and older with moderate to severe atopic dermatitis affecting at least 10% of body surface area; over 80% of participants were aged 18 years or over.^3,4 The ADvocate1 and 2 trials³ were identically designed 52-week trials comparing lebrikizumab monotherapy with placebo; other drug treatments were only allowed as rescue therapy. In the ADhere trial,⁴ patients in both the lebrikizumab and placebo groups received concurrent low- to mid-potency topical corticosteroids (initiated at baseline and tapered or stopped at the patients' discretion). The lebrikizumab dose regimen was the same in all 3 trials (500 mg loading dose given at weeks 0 and 2, followed by 250 mg every 2 weeks until week 16). Table 1 describes the primary and secondary efficacy outcomes.

Table 1 Efficacy outcomes of pivotal phase 3 placebo-controlled lebrikizumab clinical trials^3,4

Trial	Treatment group	Primary outcome: % of patients with Investigator's Global Assessment score of 0 or 1 at week 16 [NB1]	Secondary outcome: % of patients with at least a 75% improvement in Eczema Area and Severity Index at week 16 [NB2]
ADvocate1 (n=424)	lebrikizumab	43.1%	58.8%
	placebo	12.7%	16.2%
ADvocate2 (n=427)	lebrikizumab	33.2%	52.1%
	placebo	10.8%	18.1%
ADhere (n=238)	lebrikizumab + topical corticosteroid	41.2%	69.5%
	placebo + topical corticosteroid	22.1%	42.2%
NB1: Investigator's Global Assessment (IGA) score of 0 or 1 indicates clear or almost clear skin. The maximum IGA score = 4 (severe disease); all participants had an IGA score of at least 3 at baseline. NB2: Eczema Area and Severity Index (EASI) is scored out of 72, with higher values indicating greater severity and extent of disease; all participants had an EASI score of at least 16 at baseline.

Use of rescue medication was 2 to 3 times higher in the placebo groups than the treatment groups in all 3 trials.^3,4

In the ADvocate1 and 2 trials, after week 16, patients who had responded to lebrikizumab without rescue therapy were randomised again to receive lebrikizumab 2-weekly, lebrikizumab 4-weekly, or placebo (i.e. lebrikizumab stopped). Efficacy findings at week 52 were generally similar for the 2 lebrikizumab dosing regimens, with approximately 75% of patients maintaining their response while receiving treatment, compared with around half of those randomised to placebo.⁵

Lebrikizumab demonstrated sustained efficacy in a 100-week extension study in patients receiving lebrikizumab 2-weekly or 4-weekly.⁶

Adverse effects:
In the three phase 3 clinical trials, the most commonly reported adverse effect was conjunctivitis, which occurred in approximately 6.5% of lebrikizumab-treated patients (compared with 1.8% of those who received placebo).⁷ A small number of patients experienced keratitis. Most cases of conjunctivitis and keratitis were mild or moderate in severity and they recovered or resolved without treatment interruption.⁷

Other frequently observed adverse effects included nasopharyngitis, headache, injection-site reactions, and herpes zoster infection; most were mild to moderate in severity.

Serious adverse effects were rare and occurred at similar rates between treatment and control groups. Discontinuation due to adverse effects was infrequent.

Dosage and administration:
Initial: 500 mg subcutaneously at week 0 and week 2. The 500 mg doses each require 2 injections.

Induction: 250 mg subcutaneously every 2 weeks until week 16.

Maintenance: Consider discontinuing treatment in patients who have shown no clinical response after 16 weeks of treatment. For patients who achieve an adequate clinical response at week 16, the maintenance dose is 250 mg every 4 weeks. If response is partial, consider continuing to administer 250 mg every 2 weeks until an adequate response is achieved, then reduce the frequency to every 4 weeks.⁷

Lebrikizumab can be self-injected or administered by a health professional.⁷ It is not intended for episodic use.²

Use in pregnancy and breastfeeding:
Pregnancy: Lebrikizumab is a category B1 drug. Although no increase in fetal malformation or other direct or indirect harm has been observed, there are limited safety data related to pregnancy. Human IgG is known to cross the placental barrier.

Breastfeeding: Human IgG is known to be excreted in breast milk. There are limited data on the use of lebrikizumab during breastfeeding.

Place in therapy:
Lebrikizumab joins a growing class of targeted biological therapies and small molecules that address the underlying immune dysregulation in atopic dermatitis. It offers another option for patients 12 years or older with chronic moderate to severe atopic dermatitis who require systemic treatment. Lebrikizumab potentially causes less conjunctivitis than dupilumab,³ and may offer a safer long-term option compared with JAK inhibitors. While JAK inhibitors can provide faster symptom relief, they are associated with higher risks of serious adverse effects (e.g. infection, thrombosis).⁸

Practice points:
Lebrikizumab should be initiated by a dermatologist or physician with expertise in the management of atopic dermatitis.⁷ Treatment response should be assessed at week 16, with dose adjustments made as appropriate, or therapy stopped if there is inadequate clinical benefit. Patients should be educated on proper injection technique and advised to report new or worsening symptoms of conjunctivitis or keratitis to their healthcare professional. Consider completion of all age-appropriate immunisations before starting treatment; avoid administering live vaccines before and during lebrikizumab therapy.⁷

This new drug comment was finalised on 8 September 2025.

At the time this new drug comment was prepared, the Australian Public Assessment Report was available from the Therapeutic Goods Administration. The sponsor did not provide the Clinical Evaluation Report.

 

References

1. Ross G. Treatments for atopic dermatitis. Aust Prescr 2023;46:9-12.
2. Therapeutic Goods Administration. Australian Public Assessment Report for Ebglyss. Department of Health, Disability and Ageing; 2024. [cited 2025 Aug 21]
3. Silverberg JI, Guttman-Yassky E, Thaci D, Irvine AD, Stein Gold L, Blauvelt A, et al. Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis. N Engl J Med 2023;388:1080-91.
4. Simpson EL, Gooderham M, Wollenberg A, Weidinger S, Armstrong A, Soung J, et al. Efficacy and Safety of Lebrikizumab in Combination With Topical Corticosteroids in Adolescents and Adults With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial (ADhere). JAMA Dermatol 2023;159:182-91.
5. Blauvelt A, Thyssen JP, Guttman-Yassky E, Bieber T, Serra-Baldrich E, Simpson E, et al. 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 2023;188:740-8.
6. Guttman-Yassky E, Weidinger S, Simpson EL, Gooderham M, Irvine AD, Spelman L, et al. Two-Year Efficacy and Safety of Lebrikizumab in Patients with Moderate-to-Severe Atopic Dermatitis: A Long-Term Extension (ADjoin). Dermatology and Therapy 2025;15:2217-32.
7. Therapeutic Goods Administration. Australian Product Information - EBGLYSS lebrikizumab 250 mg/2 mL solution for injection autoinjector (pre-filled pen). Department of Health, Disability and Ageing; 2024. [cited 2025 Aug 21]
8. Drucker AM, Lam M, Prieto-Merino D, Malek R, Ellis AG, Yiu ZZN, et al. Systemic Immunomodulatory Treatments for Atopic Dermatitis: Living Systematic Review and Network Meta-Analysis Update. JAMA Dermatol 2024;160:936-44.

 

The new drug comments in Australian Prescriber are prepared by the editors and reviewed by the Editorial Advisory Committee. Some of the views expressed on newly approved products should be regarded as preliminary, as there may be limited published data at the time of publication, and little experience in Australia of their safety or efficacy. Before new drugs are prescribed, it is important that more detailed information is obtained from the approved product information, a medicines information centre or some other appropriate source.

Report all suspected adverse reactions to new drugs to enable continued monitoring of their benefit–harm balance.