Understanding the immune landscape in atopic dermatitis: The era of biologics and emerging therapeutic approaches

Moyle, Matthew; Cevikbas, Ferda; Harden, Jamie L.; Guttman‐Yassky, Emma

doi:10.1111/exd.13911

Cited by 128 publications

(163 citation statements)

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“…68 A similar retrospective study reported that after 8-12 weeks of treatment, 36.8% of patients treated with methotrexate for hand eczema showed a good effect of treatment. 71 The general safety precautions with methotrexate therapy should be observed, such as monitoring the serum liver enzymes and complete blood count, as well as the cumulative dosage; a weekly dose of 30 mg should not be exceeded.…”

Section: Methotrexatementioning

confidence: 99%

Hand eczema: treatment

Elsner

Agner

2019

Acad Dermatol Venereol

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Hand eczema is a highly prevalent, multietiological disease with a wide spectrum of severity and chronicity. The treatment of hand eczema, especially in severe and chronic cases, is a challenge to the dermatologist requiring not only diagnostic and therapeutic, but also excellent patient communication skills. This review discusses the spectrum of therapeutic options for hand eczema, the evidence for their efficacy and safety, and proposes a stepwise approach of intensity of treatment depending on disease severity and chronicity. In the near future, hand eczema patients may benefit from new therapeutic principles such as biologics for the treatment of atopic eczema and topical Janus Kinase inhibitors.

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Section: Methotrexatementioning

confidence: 99%

Hand eczema: treatment

Elsner

Agner

2019

Acad Dermatol Venereol

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“…They probably have a pathogenic role, triggering eosinophil and mast cells degranulation, and their titre seems to correlate with disease activity (Cozzani, Gasparini, Di Zenzo, & Parodi, 2018;Maglie & Hertl, 2019). IgE subtype antibodies are known to be associated with Th2 cells regulation, via IL-4 and IL-13 stimulation (Moyle et al, 2019). In fact, BP patients show a predominant type-2 response, suggesting that Th2 cells are primary involved in the loss of tolerance against BP180 (Cozzani et al, 2018;Maglie & Hertl, 2019).…”

Section: Bullous Pemphigoidmentioning

confidence: 99%

“…Circulating IgE anti-BMZ were also detected (Corti et al, 2018). The production of IgE class antibodies is well known to be amplified by both IL-4 and IL-13 stimulation (Moyle et al, 2019). At least for ocular MMP, three distinct pathogenic phases are described: the injury phase, with autoantibodies binding to autoantigens, activating an immunological cascade; then the acute inflammation phase, with neutrophils and proinflammatory cytokines (IL-1, TNFa, and IL-17) playing a crucial role, while Th1 cells produce IL-2 and interferon gamma, and Th2 cells release IL-4, IL-5, and IL-13; the production of these Th2-related cytokines leads to the fibrosis phase, with fibroblasts proliferating and producing extracellular matrix, connective tissue growth factor and TGFβ, causing fibrosis and mucosal scarring (Georgoudis et al, 2019).…”

Section: Mucous Membrane Pemphigoidmentioning

confidence: 99%

“…Both cytokines are produced by Th2-polarized T cells, granulocytes, and monocytes/macrophages, and have the potential to activate Th2 T cells differentiation, M2 macrophage polarization, MHCII expression, B cell and plasma cell differentiation (McCormick & Heller, 2015). Moreover, both IL-4 and IL-13 amplify IgE production from plasma cells (Moyle, Cevikbas, Harden, & Guttman-Yassky, 2019). IL-4 and IL-13 share receptor subunits (IL4Rα) and signaling molecules.…”

Section: Introductionmentioning

confidence: 99%

“…A recent study demonstrated the presence of tissue-bond IgE deposits in lesions from patients with MMP; in one patient, the IgE positivity was the only one recorded. The production of IgE class antibodies is well known to be amplified by both IL-4 and IL-13 stimulation(Moyle et al, 2019). Circulating IgE anti-BMZ were also detected(Corti et al, 2018).…”

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confidence: 99%

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Targeting interleukin 4 receptor α: A new approach to the treatment of cutaneous autoimmune bullous diseases?

Russo

Cozzani

Gasparini

et al. 2020

Dermatologic Therapy

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Bullous pemphigoid, mucous membrane pemphigoid, and pemphigus vulgaris are different cutaneous autoimmune blistering diseases, with complex pathogenic mechanisms. In all of them, a type-2 response is thought to have a central role. Interleukin 4 and Interleukin 13 are crucial cytokines in type-2 response. Treatment of these conditions is often challenging. Dupilumab, a recombinant fully human IgG4 monoclonal antibody with binding specificity to human interleukin-4 receptor IL-4Rα, has the potential to inhibit both IL-4 and IL-13. We propose IL-4Rα as a theoretical drug target for cutaneous autoimmune bullous diseases. K E Y W O R D Sblistering diseases, bullous pemphigoid, dupilumab, mucous membrane pemphigoid, pemphigus vulgaris

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Efficacy and Safety of Lebrikizumab, a High-Affinity Interleukin 13 Inhibitor, in Adults With Moderate to Severe Atopic Dermatitis

et al. 2020

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IMPORTANCE Interleukin 13 (IL-13) is a central pathogenic mediator driving multiple features of atopic dermatitis (AD) pathophysiology.OBJECTIVE To evaluate the efficacy and safety of lebrikizumab, a novel, high-affinity, monoclonal antibody targeting IL-13 that selectively prevents formation of the IL-13Rα1/IL-4Rα heterodimer receptor signaling complex, in adults with moderate to severe AD. DESIGN, SETTING, AND PARTICIPANTSA phase 2b, double-blind, placebo-controlled, dose-ranging randomized clinical trial of lebrikizumab injections every 4 weeks or every 2 weeks was conducted from January 23, 2018, to May 23, 2019, at 57 US centers. Participants were adults 18 years or older with moderate to severe AD.INTERVENTIONS Patients were randomized 2:3:3:3 to placebo every 2 weeks or to subcutaneous injections of lebrikizumab at the following doses: 125 mg every 4 weeks (250-mg loading dose [LD]), 250 mg every 4 weeks (500-mg LD), or 250 mg every 2 weeks (500-mg LD at baseline and week 2). MAIN OUTCOMES AND MEASURESThe primary end point was percentage change in the Eczema Area and Severity Index (EASI) (baseline to week 16). Secondary end points for week 16 included proportion of patients achieving Investigator's Global Assessment score of 0 or 1 (IGA 0/1); EASI improvement of at least 50%, 75%, or 90% from baseline; percentage change in the pruritus numeric rating scale (NRS) score; and pruritus NRS score improvement of at least 4 points. Safety assessments included treatment-emergent adverse events.RESULTS A total of 280 patients (mean [SD] age, 39.3 [17.5] years; 166 [59.3%] female) were randomized to placebo (n = 52) or to lebrikizumab at doses of 125 mg every 4 weeks (n = 73), 250 mg every 4 weeks (n = 80), or 250 mg every 2 weeks (n = 75). Compared with placebo (EASI least squares mean [SD] percentage change, −41.1% [56.5%]), lebrikizumab groups showed dose-dependent, statistically significant improvement in the primary end point vs placebo at week 16: 125 mg every 4 weeks (−62.3% [37.3%], P = .02), 250 mg every 4 weeks (−69.2% [38.3%], P = .002), and 250 mg every 2 weeks (−72.1% [37.2%], P < .001). Differences vs placebo-treated patients (2 of 44 [4.5%]) in pruritus NRS improvement of at least 4 points were seen as early as day 2 in the high-dose lebrikizumab group (9 of 59 [15.3%]). Treatment-emergent adverse events were reported in 24 of 52 placebo patients (46.2%) and in lebrikizumab patients as follows: 42 of 73 (57.5%) for 125 mg every 4 weeks, 39 of 80 (48.8%) for 250 mg every 4 weeks, and 46 of 75 (61.3%) for 250 mg every 2 weeks; most were mild to moderate and did not lead to discontinuation. Low rates of injection-site reactions (1 of 52 [1.9%] in the placebo group vs 13 of 228 [5.7%] in all lebrikizumab groups), herpesvirus infections (2 [3.8%] vs 8 [3.5%]), and conjunctivitis (0% vs 6 [2.6%]) were reported.CONCLUSIONS AND RELEVANCE During 16 weeks of treatment, lebrikizumab provided rapid, dose-dependent efficacy across a broad range of clinical manifestations in adult patients with moderate to severe ...

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Understanding the immune landscape in atopic dermatitis: The era of biologics and emerging therapeutic approaches

Cited by 128 publications

References 155 publications

Hand eczema: treatment

Hand eczema: treatment

Targeting interleukin 4 receptor α: A new approach to the treatment of cutaneous autoimmune bullous diseases?

Efficacy and Safety of Lebrikizumab, a High-Affinity Interleukin 13 Inhibitor, in Adults With Moderate to Severe Atopic Dermatitis

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