Biologics for Treatment of Atopic Dermatitis: Current Status and Future Prospect

Abstract

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by intense pruritus and recurrent eczematous lesions that significantly impair quality of life. It is a heterogeneous disease affecting both children and adults. The treatment of moderate-to-severe forms of AD is challenging, as topical corticosteroids are often insufficient to achieve disease control or inappropriate and off-label use of immunosuppressants may have significant undesirable side effects. The development of targeted biologic therapies specifically for AD is thus highly desirable. Dupilumab is the only biologic therapy that is Food and Drug Administration approved for the treatment of moderate-to-severe AD in patients 6 years and older, with consistent long-term efficacy and safety trial data. In this article, we review the mechanisms, safety, and efficacy of dupilumab from recent clinical trials, and we review the current data, mechanism of action, clinical efficacy, and limitations of new biologics currently in phase 2 and 3 clinical trials (lebrikizumab, tralokinumab, nemolizumab, tezepelumab, and ISB 830).

Keywords: Atopic dermatitis; Biologic therapy; Dupilumab; Eczema; GBR 830; ISB 830; Lebrikizumab; Nemolizumab; Tezepelumab; Tralokinumab.

FIGURE 1.

Atopic dermatitis pathogenesis and targets of biologics approved and in clinical development for atopic dermatitis. DC, Dendritic cell; IFN, interferon; IgE, immunoglobulin E; IL, interleukin; ILC, innate lymphoid cell; LC, langerhans cell; Th, T-helper; TNF, tumour necrosis factor; TSLP, thymic stromal lymphopoietin.

FIGURE 2.

Step-care management of atopic dermatitis (AD). Acute and maintenance treatments for AD across the spectrum of disease severity. ^aFor patients aged ≥2 years with mild-to-moderate AD. ^bFor patients aged ≥6 years with moderate-to-severe AD. ^cNot approved by the Food and Drug Administration to treat AD. ^dNot recommended for long-term maintenance. TCI, Topical calcineurin inhibitor; TCS, topical corticosteroid. Adapted from Fishbein et al.

FIGURE 3.

Primary endpoint (A) and key efficacy endpoints (B, C) of phase 3 trials of dupilumab for the treatment of moderate-to-severe atopic dermatitis. A, The proportions of patients who achieved IGA 0/1 with ≥2 reductions from baseline at week 16 among patients who received dupilumab q1w, q2w, or placebo in SOLO 1 and SOLO 2. Proportions of patients who achieved IGA 0/1 at week 16 among were a primary endpoint for AD-1526. B, The proportions of patients who achieved EASI-75 at week 16 among patients who received dupilumab and placebo. EASI-75 was a co-primary endpoint in CHRONOS. C, The proportions of patients with ≥4-point improvement in peak pruritus NRS score from baseline at week 16 among patients who received dupilumab and placebo. P < .001 for all comparisons with placebo in SOLO1/SOLO2. P < .0001 for all comparisons with placebo in CHRONOS. P < .001 for all comparisons with placebo in AD-1526. EASI-75, Greater than 75% improvement in Eczema Area and Severity Index score; IGA, Investigator’s global assessment; NRS, numeric rating scale; q1w, every week; q2w, every other week. *In CHRONOS, patients also received concomitant topical corticosteroid in every treatment arm. **In AD-1526, patients received dupilumab every 2 weeks (green), every 4 weeks (blue), or placebo.