The New Era of Biologics in Atopic Dermatitis: A Review.
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ABSTRACT:
SUBMITTER: Schneider S
PROVIDER: S-EPMC8648434 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disease driven by immune dysregulation and skin barrier dysfunction. We are currently experiencing a new era of understanding of the pathogenesis of AD and, as a consequence, a new era of innovation in therapeutics, including small molecules and biologic therapy. Recently, advances in translational research have challenged the traditional AD pathogenesis paradigm of AD being solely a Th2-dominant disease. Other immune pathways seem to play a role in the complex AD pathophysiology, although the clinical relevance of these additional immune pathway abnormalities is unclear. Type 1, type 22, and type 17 pathway activation (with related cytokines/chemokines) have been demonstrated in the skin and blood of AD patients. Type 2 (interleukin [IL]-4, IL-13), IL-31, and type 22 (IL-22) pathway cytokines are increased in AD acute lesions. IL-22 induces both an epidermal hyperplasia at the onset of acute AD and a marked increase in the terminal differentiation S100 genes. This understanding of pathogenesis corresponds to a historic increase in therapeutic development in AD. The extreme clinical heterogeneity and the chronic progression of AD establish the need for newer, safer, and more effective treatments, control the disease, and improve the quality of life of affected patients.
| S-EPMC7875213 | biostudies-literature
Project description:The era of biologics for the treatment of moderate-to-severe atopic dermatitis (AD) began in 2017 with the approval of dupilumab, a monoclonal antibody that binds to the α-subunit of the interleukin IL-4 receptor. Until then, only conventional immunosuppressants were available for systemic treatment, of which only cyclosporine is approved for the treatment of severe AD. In the meantime, the therapeutic landscape of AD has been changing rapidly, and additional biologics have been developed which target IL-13, the IL-31 receptor, OX40, and OX40L, among others. Many of these substances have already shown promising results in phase 1, 2, and in some cases also phase 3 trials. In June 2021, tralokinumab, an IL-13 antibody, has been approved in Europe for the treatment of moderate-to-severe AD in adults. In addition to antibody-based therapies, "small molecules" that, e.g., inhibit Janus kinases enrich the armamentarium of systemic AD therapies. With all these agents, not only will many more targeted therapies become available, but also will the complex and heterogeneous pathophysiological processes of this disease be better understood.
| S-EPMC8439107 | biostudies-literature
Project description:Atopic dermatitis (AD) is a chronic, inflammatory skin disease with an eczematous rash and itching. Due to undesired adverse effects of traditional systemic treatment, there is still an unmet need for safe and effective long-term therapy for refractory AD. As our understanding of the pathogenesis underlying AD grows, novel treatments targeting specific molecules have been developed. Here, we discuss the efficacy and safety profiles of these drugs in recent clinical trials. Among their adverse effects, of particular note is AD acceleration. Although there is still debate about whether certain adverse reactions can be said to be paradoxical adverse events (PAEs), a wide range of PAEs have been reported during biological treatment for chronic immune-mediated diseases. Close surveillance of novel biologics is crucial to detect new undescribed paradoxical reactions and to shed light on the convoluted pathogenesis of AD.
| S-EPMC8181104 | biostudies-literature
Project description:Atopic dermatitis (AD) is a chronic, systemic, inflammatory disease that affects the skin and is characterized by persistent itch and marked redness. AD is associated with an increased risk of skin infections and a reduced quality of life. Most AD treatment options to date were not designed to selectively target disease-causing pathways that have been established for this indication. Topical therapies have limited efficacy in moderate-to-severe disease, and systemic agents such as corticosteroids and immunosuppressants present with tolerability issues. Advances in the understanding of AD pathobiology have made possible a new generation of more disease-specific AD therapies. AD is characterized by the inappropriate activation of type 2 T helper (Th2) cells and type 2 innate lymphoid (ILC2) cells, with a predominant increase in type 2 cytokines in the skin, including interleukin (IL)-13 and IL-4. Both cytokines are implicated in tissue inflammation and epidermal barrier dysfunction, and monoclonal antibodies targeting each of these interleukins or their receptors are in clinical development in AD. In March 2017, dupilumab, a human anti-IL-4Rα antibody, became the first biologic to receive approval in the United States for the treatment of moderate-to-severe AD. The anti-IL-13 monoclonal antibodies lebrikizumab and tralokinumab, which bind different IL-13 epitopes with potentially different effects, are currently in advanced-stage trials. Here, we briefly review the underlying pathobiology of AD, the scientific basis for current AD targets, and summarize current clinical studies of these agents, including new research to develop both predictive and response biomarkers to further advance AD therapy in the era of precision medicine.
| S-EPMC6850480 | biostudies-literature
Project description:Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disease driven by immune dysregulation and skin barrier dysfunction. Currently, we are experiencing a new era of understanding of the pathogenesis of AD and, as a consequence, a new era of innovation in therapeutics, including small molecules and biologic therapy. In contrast to biologics, small molecules are similar to conventional pharmacologic chemical agents used as drugs and are generally prepared by chemical synthesis. Unlike biologics, these drugs often are taken orally or formulated for topical use. The purpose of this review is to summarize the efficacy and safety of the current topical and systemic new therapies in AD by reviewing recently published papers on therapies currently in phase 2 or 3 clinical trials. In this review, it is important to note the characteristics of the study population, the primary endpoints, and whether or not there was concomitant topical therapy allowed. These study design elements may significantly alter the results of studies and should be taken into account. Targeted therapy help push AD treatment into a new era of personalized medicine.
| S-EPMC8082001 | biostudies-literature
Project description:Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, and the condition is typified by barrier dysfunction and immune dysregulation. Recent studies have characterized various phenotypes and endotypes of AD and elucidated the mechanism. Numerous topical and systemic narrow targeting therapies for AD have been developed according to these findings. Topical medications, including Janus kinase (JAK) inhibitors, phosphodiesterase 4 inhibitors, and the aryl hydrocarbon receptor agonist tapinarof, are effective and safe for AD compared to topical corticosteroids. Oral JAK inhibitors and monoclonal antibodies targeting interleukin (IL)-4, IL-13, IL-31, IL-33, OX40, thymic stromal lymphopoietin, and sphingosine 1-phosphate signaling have displayed outstanding efficacy against moderate-to-severe AD. We are currently in a new era of AD treatment.
| S-EPMC9605067 | biostudies-literature
Project description:BackgroundAtopic dermatitis is a chronic pruritic inflammatory skin disease commonly occurring in children. The objective of this study is to evaluate the treatment of pediatric atopic dermatitis with biologics, as they have displayed immense promising results in several recent clinical trials on atopic dermatitis (AD).MethodsWe will conduct an extensive search for RCTs in several databases, including Embase, Cochrane Library, Web of Science, and PubMed, from the inception of the study till 15th May 2022. The primary outcomes will be the proportion of patients with EASI 75/90/100 after 12-16 weeks of treatment. The secondary outcomes will include the Numerical Rating Scale (NRS), Investigator Global Assessment (IGA)0-1, body surface area (BSA), Dermatology Life Quality Index (DLQI) scores, and incidence of adverse reactions. All studies will be screened by two independent researchers. They will assess the risk of bias in the included studies according to the RCTs bias risk evaluation tool in Cochrane System Review Manual 5.1.0. Meta-analysis will be performed using RevMan V.5.3.0 software.ResultsThe research results will provide a reference for the clinical application of biological agents in pediatric atopic dermatitis.ConclusionWe aim to evaluate the efficacy and safety of biologics in pediatric atopic dermatitis cases and provide evidence-based data for easy clinical application.Prospero registration numberCRD42022319052 (https://www.crd.york.ac.uk/PROSPERO/#joinuppage).
| S-EPMC9897544 | biostudies-literature
Project description: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).
| S-EPMC7951162 | biostudies-literature
Project description:Genomic imprinting is a genetic process where only one allele of a particular gene is expressed in a parent-of-origin dependent manner. Epigenetic changes in the DNA, such as methylation or acetylation of histones, are primarily thought to be responsible for silencing of the imprinted allele. Recently, global CpG methylation changes have been identified in psoriatic skin in comparison to normal skin, particularly near genes known to be upregulated in psoriasis such as KYNU, OAS2, and SERPINB3. Furthermore, imprinting has been associated with multi-chromosomal human disease, including diabetes and multiple sclerosis. This paper is the first to review the clinical and genetic evidence that exists in the literature for the association between imprinting and general skin disorders, including atopic dermatitis and psoriatic disease. Atopy was found to have evidence of imprinting on chromosomes 6, 11, 14, and 13. The ? subunit of the IgE receptor on chromosome 11q12-13 may be imprinted. Psoriatic disease may be related to imprinting effects on chromosome 6 for psoriasis and 16 for psoriatic arthritis.
| S-EPMC4679559 | biostudies-other
Project description:Recent evidence showed that the postulated linear progression of the atopic march, from atopic dermatitis to food and respiratory allergies, does not capture the heterogeneity of allergic phenotypes, which are influenced by complex interactions between environmental, genetic, and psychosocial factors. Indeed, multiple atopic trajectories are possible in addition to the classic atopic march. Nevertheless, atopic dermatitis is often the first manifestation of an atopic march. Improved understanding of atopic dermatitis pathogenesis is warranted as this could represent a turning point in the prevention of atopic march. In this review, we outline the recent findings on the pathogenetic mechanisms leading to atopic dermatitis that could be targeted by intervention strategies for the prevention of atopic march.
| S-EPMC9029734 | biostudies-literature