Dupilumab: First Global Approval

Shirley, Matt

doi:10.1007/s40265-017-0768-3

Cited by 134 publications

(93 citation statements)

References 10 publications

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“…For this purpose, two different monoclonal antibodies have been evaluated, reslizumab and mepolizumab (14) . Lastly, dupilumab is a human monoclonal antibody (mAb) that binds to the IL-4 receptor alpha subunit (IL-4Rα) inhibiting signaling of both IL-4 and IL-13 (15) , two type 2 helper T-cell (Th2) associated cytokines that play a major role in the pathogenesis of nasal polyposis. This type of biologic therapy has previously shown clinical benefit in patients with asthma and atopic dermatitis and could not have been omitted in the research of nasal polyposis (16,17) .…”

Section: Introductionmentioning

confidence: 99%

Monoclonal antibodies for the treatment of chronic rhinosinusitis with nasal polyposis: a systematic review

Tsetsos

Goudakos

Daskalakis

et al. 2018

Rhin

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Background: Μonoclonal antibodies have been proposed as a novel therapy in patients suffering from chronic rhinosinusitis with nasal polyposis (CRSwNP). The purpose of this systematic review was to evaluate their efficacy and safety.Methodology: A literature search was performed in MEDLINE, Web of Science, the Cochrane Library and multiple trial registries followed by extensive hand-searching for the identification of relevant studies. Only randomized controlled trials (RCTs) comparing the use of monoclonal antibodies with placebo or another therapy in adult patients with CRSwNP were included.Results: Anti-immunoglobin E (IgE) therapy with omalizumab was assessed in two studies, anti-interleukin (IL)-5 therapy in three studies (1 reslizumab, 2 mepolizumab) and finally anti-IL-4 and anti-IL-13 therapy in only one. With the exception of one study, biologic therapy was proved to be effective in reducing total nasal endoscopic polyp score (TPS) in treatment as compared to placebo groups. Monoclonal antibodies brought about improvement in several other outcomes, such as opacification in computed tomography (CT), quality of life measures, nasal airflow, olfaction and type 2 helper T-cell (Th2) associated biomarkers. Overall, the use of these agents was deemed safe and well-tolerated.Conclusions: This is the first systematic review showing encouraging results for the use of all three main categories of monoclonal antibodies in CRSwNP patients and highlights the need for further well-designed and with larger sample sizes RCTs.

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Section: Introductionmentioning

confidence: 99%

Monoclonal antibodies for the treatment of chronic rhinosinusitis with nasal polyposis: a systematic review

Tsetsos

Goudakos

Daskalakis

et al. 2018

Rhin

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“…In refractory cases, systemic therapy becomes a necessity. Promising results have been achieved using the IL-4 receptor antagonist dupilumab, which has been approved by the EMU/FDA in 2017 (88, 89). In selected severe, otherwise refractory cases, the use of rituximab or intravenous IgG (IVIG) might be an option.…”

Section: Indicationsmentioning

confidence: 99%

Extracorporeal Photopheresis—An Overview

2018

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Extracorporeal photopheresis (ECP) has been in clinical use for over three decades after receiving FDA approval for the palliative treatment of the Sézary Syndrome variant of cutaneous T-cell lymphoma (CTCL) in 1988. After the first positive experiences with CTCL, additional indications have been successfully explored including areas such as graft-vs.-host disease (GVHD), scleroderma, and solid organ transplantation. The mechanism of action is still not fully resolved, but important steps in understanding ECP in recent years have been very informative. Originally, the primary hypothesis stated that psoralen and ultraviolet A (UVA) in combination induce apoptosis in the treated immune cells. This view shifted in favor of dendritic cell initiation, modification of the cytokine profile and stimulation of several T-cell lineages, in particular regulatory T-cells. A number of ECP guidelines have been produced to optimize treatment regimens in the clinical context. In CTCL, enough evidence is available for the use of ECP as a first line treatment for Sézary Syndrome (SS), but also as a second line or rescue treatment in therapy-refractory forms of mycosis fungoides (MF). ECP in the treatment of acute and chronic GVHD has shown promising results as second line therapy in steroid-refractory presentations. In solid organ transplantation, ECP has been used to increase tissue tolerance and decrease infections with opportunistic pathogens, attributed to the use of high doses of immunosuppressive medication. Infection with cytomegalovirus (CMV) remains a limiting factor affecting survival in solid organ transplantation and the role of ECP will be discussed in this review. A trend toward prophylactic use of ECP can be observed and may further contribute to improve the outcome in many patients. To further deepen our knowledge of ECP and thus facilitate its use in patients that potentially benefit most from it, future prospective randomized trials are urgently needed in this rapidly growing field. The aim of this review is to (1) introduce the method, (2) give an overview where ECP has shown promising effects and has become an essential part of treatment protocols, and (3) to give recommendations on how to proceed in numerous indications.

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“…IL‐4 binds to both type I and II receptors, while IL‐13 has affinity to type II and IL‐13Rα2. Dupilumab is an IL‐4 Rα‐antagonist that inhibits IL‐4 and IL‐13 signaling through blockade of the shared IL‐4α subunit …”

Section: Il‐4/il‐13 and Their Receptorsmentioning

confidence: 99%

“…Dupilumab is an IL-4 Rαantagonist that inhibits IL-4 and IL-13 signaling through blockade of the shared IL-4α subunit. 17 In addition to allergy, IL-4/IL-13 regulates the immune microenvironment in cancer. Signaling via type II receptor induces tumor proliferation, cell survival, cell adhesion, and metastasis.…”

Section: Il-4/il-13 and Their Recep Tor Smentioning

confidence: 99%

Atopic dermatitis as Th2 disease revisited

Tokura

Phadungsaksawasdi

Ito

2018

J Cutaneous Imm & Allergy

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T helper 1 (Th1) and T helper 2 (Th2) populations are a classical dichotomy to understand the immunological disorders, and this concept remains vital in atopic dermatitis (AD). While IL‐4 and IL‐13 are produced mainly by Th2 cells, mast cells, and basophils, these cytokines target these producers, indicating the presence of autocrine and paracrine stimulation. There are two types of receptors for IL‐4 and IL‐13, type I and type II. IL‐4 binds to both type I and II receptors, while IL‐13 has affinity to type II. Dupilumab is an IL‐4Rα‐antagonist that inhibits IL‐4 and IL‐13 signaling through blockade of the shared IL‐4α subunit. The Th2‐stimulating effect of thymic stromal lymphopoietin (TSLP) is triggered by its binding to TSLP receptor (TSLPR) on Th2 cells. The frequency of TSLPR+CD4+ T cells correlates with disease activity. CD4+ T cells directly interact with TSLP to produce a high amount of IL‐4. Conversely, IL‐4 induces TSLPR expression in T cells. Moreover, TSLP and IL‐4 promote CCR4 expression, which is a chemokine receptor for CCL17/TARC. Langerhans cells initiate epicutaneous sensitization with protein antigens and induce Th2 cell–mediated immune responses via TSLP signaling. Filaggrin deficiency, which cornified layer‐damaged skin allows protein antigens to penetrate through the stratum corneum, leads to allergy where IL‐4 and IL‐13 are overproduced. Subsequently, IL‐4 and IL‐13 further depress filaggrin expression with vicious cycle. AD is generally a Th2 disease, but there exist several exceptional and undeniable facts to be considered, including Th1‐activated intrinsic AD, Th1‐infiltrating chronic AD skin lesions, and Th17 involvement.

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Dupilumab: First Global Approval

Cited by 134 publications

References 10 publications

Monoclonal antibodies for the treatment of chronic rhinosinusitis with nasal polyposis: a systematic review

Monoclonal antibodies for the treatment of chronic rhinosinusitis with nasal polyposis: a systematic review

Extracorporeal Photopheresis—An Overview

Atopic dermatitis as Th2 disease revisited

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