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Pharmaceutics
Special Issues
New and Emerging Target-Oriented Drugs for Atopic Dermatitis
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New and Emerging Target-Oriented Drugs for Atopic Dermatitis

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biologics and Biosimilars".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 26642

Special Issue Editor

Prof. Dr. Tiago Torres

E-Mail Website
Guest Editor
1. Department of Dermatology, Centro Hospitalar Universitário do Porto, Porto, Portugal
2. Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
Interests: psoriasis; atopic dermatitis; immunemediated diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Atopic dermatitis (AD) is a clinically heterogenous inflammatory skin condition that has a great impact

on patients’ daily activities that remains difficult to treat. The pathophysiology of AD is thought to be a result of the interaction between various critical factors, such as epidermal barrier disruption, genetic susceptibility, activation of distinct subsets of T-cells, environmental triggers, and dysbiosis of commensal skin microbiota.

The knowledge acquired over the last decade on AD pathophysiology has led to the development of new targeted therapeutic options, including biologic agents and small molecules, that enable clinicians to better manage AD patients. The main therapeutic targets include cytokines related to Th2 inflammation and their intracellular JAK-STAT signalling pathway, but many other agents (topical, oral, and parenteral drugs) with different targets are in the pipeline.

This Special Issue aims to review recent and future therapy development for the treatment of atopic dermatitis. 

Prof. Dr. Tiago Torres
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • atopic dermatitis
  • biologic drugs
  • small-molecules
  • IL-4
  • IL-13
  • IL-31
  • JAK-STAT pathway
  • dupilumab
  • lebrikizumab
  • tralokinumab
  • abrocitinib
  • upadaitinb
  • baricitinb
  • pipeline

Published Papers (7 papers)

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Research

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14 pages, 1360 KiB  
Article
Association between Dupilumab and Conjunctivitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
by Tzu-Yi Lin, Ching-Ya Wang, Fang-Ying Wang, Eugene Yu-Chuan Kang and Yih-Shiou Hwang
Pharmaceutics 2023, 15(4), 1031; https://doi.org/10.3390/pharmaceutics15041031 - 23 Mar 2023
Cited by 1 | Viewed by 2285
Abstract
Conjunctivitis is commonly reported in dupilumab users with atopic dermatitis (AD), and few studies have compared the risk of conjunctivitis among patients with different indications. This study aimed to investigate the association between dupilumab and conjunctivitis in various diseases. The protocol of this [...] Read more.
Conjunctivitis is commonly reported in dupilumab users with atopic dermatitis (AD), and few studies have compared the risk of conjunctivitis among patients with different indications. This study aimed to investigate the association between dupilumab and conjunctivitis in various diseases. The protocol of this study was registered on PROSPERO (ID CRD42023396204). The electronic search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov was conducted for the period from their inception to January 2023. Only placebo-controlled, randomized controlled trials (RCTs) were included. The main outcome was the incidence of conjunctivitis during the study period. The subgroup analysis was performed for patients with AD and non-AD indications, which include asthma, chronic rhinosinusitis with nasal polyps, and eosinophilic esophagitis. In total, 23 RCTs involving 9153 patients were included for meta-analysis. Dupilumab users exhibited significantly higher risk of conjunctivitis (risk ratio [RR], 1.89; 95% confidence interval [CI], 1.34–2.67) than placebo users. Notably, significantly increased incidence of conjunctivitis was observed in the dupilumab group relative to the placebo group among patients with AD (RR, 2.43; 95% CI, 1.84–3.12) but not among patients with non-AD indications (RR, 0.71; 95% CI, 0.43–1.13). In conclusion, only dupilumab users with AD but not those with non-AD indications reported an elevated incidence of conjunctivitis. Full article
(This article belongs to the Special Issue New and Emerging Target-Oriented Drugs for Atopic Dermatitis)
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Review

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13 pages, 1322 KiB  
Review
Blockage of the IL-31 Pathway as a Potential Target Therapy for Atopic Dermatitis
by Raquel Leao Orfali and Valeria Aoki
Pharmaceutics 2023, 15(2), 577; https://doi.org/10.3390/pharmaceutics15020577 - 08 Feb 2023
Cited by 9 | Viewed by 4069
Abstract
Atopic dermatitis (AD), a pruritic, inflammatory chronic disease with multifactorial pathogenesis, has been a therapeutic challenge. Novel target treatments aim to reduce not only the immunologic dysfunction and microbiome dysbiosis but also the recovery of the damaged skin barrier. The current review focuses [...] Read more.
Atopic dermatitis (AD), a pruritic, inflammatory chronic disease with multifactorial pathogenesis, has been a therapeutic challenge. Novel target treatments aim to reduce not only the immunologic dysfunction and microbiome dysbiosis but also the recovery of the damaged skin barrier. The current review focuses on the interleukin 31 (IL-31) pathway and AD and offers an overview of the current clinical studies with monoclonal antibodies blocking this cascade. Pruritus, the key symptom of AD, has substantial participation of the IL-31 complex and activation of relevant signaling pathways. Epidermal keratinocytes, inflammatory cells, and cutaneous peripheral nerves express the interleukin-31 receptor α-chain (IL-31RA), upregulated by Staphylococcus aureus toxins or Th2 cytokines involved in AD. Nemolizumab is a humanized monoclonal antibody that antagonizes IL-31RA, inhibiting the IL-31 cascade and therefore contributing to reducing the pruritus and inflammation and recovering the damaged skin barrier in AD patients. Phases 2 and 3 clinical trials with nemolizumab in AD show a suitable safety profile, with a fast, efficient, and sustained reduction of pruritus and severity scores, especially when associated with topical treatment. Deciphering the full interplay of the IL-31 pathway and AD may expand the potential of nemolizumab as a targeted therapy for AD and other pruritic conditions. Full article
(This article belongs to the Special Issue New and Emerging Target-Oriented Drugs for Atopic Dermatitis)
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18 pages, 721 KiB  
Review
Targeting Interleukin 13 for the Treatment of Atopic Dermatitis
by Yuliya Lytvyn and Melinda Gooderham
Pharmaceutics 2023, 15(2), 568; https://doi.org/10.3390/pharmaceutics15020568 - 08 Feb 2023
Cited by 7 | Viewed by 5186
Abstract
Atopic dermatitis (AD) is a common chronic inflammatory skin condition that has a significant impact on a patient’s quality of life and requires ongoing management. Conventional topical and systemic therapies do not target specific components of AD pathogenesis and, therefore, have limited efficacy [...] Read more.
Atopic dermatitis (AD) is a common chronic inflammatory skin condition that has a significant impact on a patient’s quality of life and requires ongoing management. Conventional topical and systemic therapies do not target specific components of AD pathogenesis and, therefore, have limited efficacy and may be associated with long-term toxicity. Thus, AD management is challenging, with a significant proportion of patients not achieving clear skin or a reduction in pruritus. There remains a large unmet need for effective therapeutic strategies with favorable safety profiles that can be used long-term in patients with refractory AD. The emergence of targeted biological and small molecule therapies has effectively broadened available treatment options for moderate-to-severe AD. Most recently, interleukin 13 (IL-13) inhibitors were shown to be efficacious and well-tolerated, with tralokinumab already approved for use in this patient population. It is important for dermatologists to be aware of the evidence behind this emerging class of biologic agents to guide treatment choices and improve outcomes in patients with AD. The main objective of this paper is to review the current literature regarding the efficacy and safety of current and emerging anti-IL-13 monoclonal antibodies, including tralokinumab, lebrikizumab, cendakimab, and eblasakimab, for the treatment of moderate-to-severe AD. Full article
(This article belongs to the Special Issue New and Emerging Target-Oriented Drugs for Atopic Dermatitis)
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16 pages, 540 KiB  
Review
Efficacy and Safety of JAK1 Inhibitor Abrocitinib in Atopic Dermatitis
by Helena Iznardo, Esther Roé, Esther Serra-Baldrich and Lluís Puig
Pharmaceutics 2023, 15(2), 385; https://doi.org/10.3390/pharmaceutics15020385 - 23 Jan 2023
Cited by 9 | Viewed by 3815
Abstract
Abrocitinib is a JAK1 selective inhibitor recently approved for the treatment of moderate-to-severe atopic dermatitis in adults. It has demonstrated efficacy and safety in several clinical trials, both in children and adults, in monotherapy, and compared with dupilumab. The expected EASI-75 response rate [...] Read more.
Abrocitinib is a JAK1 selective inhibitor recently approved for the treatment of moderate-to-severe atopic dermatitis in adults. It has demonstrated efficacy and safety in several clinical trials, both in children and adults, in monotherapy, and compared with dupilumab. The expected EASI-75 response rate estimates at week 12 are 62.9% (95% CrI 42.5–79.9%) for abrocitinib 200 mg and 43.0% (95% CrI 24.8–64.0%) for abrocitinib 100 mg. Abrocitinib has shown a faster effect than dupilumab as regards early alleviation of itch. Because of the incomplete target selectivity of JAK inhibitors, when abrocitinib treatment is considered, laboratory screening is necessary, latent tuberculosis must be screened for, active infections are a contraindication, and special caution must be exerted in treating elderly patients and those predisposed to thromboembolic events. Even though recent meta-analyses of clinical trials have not shown that atopic dermatitis, or its treatment with JAK inhibitors or dupilumab, modify the risk of deep venous thrombosis or pulmonary embolism, long-term follow-up studies will better define the safety profile of abrocitinib. Full article
(This article belongs to the Special Issue New and Emerging Target-Oriented Drugs for Atopic Dermatitis)
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17 pages, 1079 KiB  
Review
Novel Therapeutic Strategies in the Topical Treatment of Atopic Dermatitis
by Lorenzo Maria Pinto, Andrea Chiricozzi, Laura Calabrese, Maria Mannino and Ketty Peris
Pharmaceutics 2022, 14(12), 2767; https://doi.org/10.3390/pharmaceutics14122767 - 10 Dec 2022
Cited by 5 | Viewed by 2755
Abstract
Topical agents that are currently available for the treatment of atopic dermatitis may represent a valid approach in the management of mild or mild–moderate cases, whereas they are often supplemented with systemic therapies for handling more complex or unresponsive cases. The most used [...] Read more.
Topical agents that are currently available for the treatment of atopic dermatitis may represent a valid approach in the management of mild or mild–moderate cases, whereas they are often supplemented with systemic therapies for handling more complex or unresponsive cases. The most used compounds include topical corticosteroids and calcineurin inhibitors, although their use might be burdened by side effects, poor response, and low patient compliance. Consequently, new innovative drugs with higher efficacy and safety both in the short and long term need to be integrated into clinical practice. A deeper understanding of the complex pathogenesis of the disease has led to identifying new therapeutic targets and to the development of innovative therapeutics. This narrative review aims to collect data on selected promising topical drugs that are in an advanced stage of development. Full article
(This article belongs to the Special Issue New and Emerging Target-Oriented Drugs for Atopic Dermatitis)
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10 pages, 472 KiB  
Review
OX40-OX40L Inhibition for the Treatment of Atopic Dermatitis—Focus on Rocatinlimab and Amlitelimab
by Ana Maria Lé and Tiago Torres
Pharmaceutics 2022, 14(12), 2753; https://doi.org/10.3390/pharmaceutics14122753 - 08 Dec 2022
Cited by 20 | Viewed by 5186
Abstract
Despite the recent emergence of targeted therapeutic options, there are still unmet needs concerning moderate-to-severe atopic dermatitis treatment. This review aims to discuss the OX40-OX40L pathway as a therapeutic target for the treatment of atopic dermatitis. OX40 and OX40L are two checkpoint molecules [...] Read more.
Despite the recent emergence of targeted therapeutic options, there are still unmet needs concerning moderate-to-severe atopic dermatitis treatment. This review aims to discuss the OX40-OX40L pathway as a therapeutic target for the treatment of atopic dermatitis. OX40 and OX40L are two checkpoint molecules that bind to potentiate pro-inflammatory T-cell responses that are pivotal to atopic dermatitis pathogenesis. Two OX40-OX40L inhibitors, rocatinlimab and amlitelimab, are being developed for the treatment of atopic dermatitis. Rocatinlimab, an anti-OX40 antibody, was evaluated in phase 2b, a randomized, placebo-controlled clinical trial. At week 16, rocatinlimab groups achieved a greater reduction in the EASI percentage change from the baseline (−48.3% to −61.1%) against the placebo (−15.0%; p < 0.001), and clinical response was maintained 20 weeks after the treatment had ceased. Amlitelimab, an anti-OX40L antibody, was studied in a 12-week treatment phase 2a clinical trial, with a significant efficacy response observed within 2 weeks. At week 16, amlitelimab groups reached the EASI mean percentage change from the baseline of −69.9% and −80.1% versus the placebo (−49.4%; p = 0.072 and p = 0.009). Among the responders, 68% of amlitelimab patients were sustained 24 weeks following the last dose. Both treatments were shown to be safe and well tolerated. Current evidence points to OX40-OX40L inhibitors as future options for atopic dermatitis treatment with potential disease-modifying effects. Full article
(This article belongs to the Special Issue New and Emerging Target-Oriented Drugs for Atopic Dermatitis)
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13 pages, 1057 KiB  
Review
Efficacy and Safety of Upadacitinib for Management of Moderate-to-Severe Atopic Dermatitis: An Evidence-Based Review
by Yuliya Lytvyn, Asfandyar Mufti, Abrahim Abduelmula, Muskaan Sachdeva, Khalad Maliyar, Jorge R. Georgakopoulos and Jensen Yeung
Pharmaceutics 2022, 14(11), 2452; https://doi.org/10.3390/pharmaceutics14112452 - 14 Nov 2022
Cited by 3 | Viewed by 2553
Abstract
Atopic dermatitis (AD) is a common skin condition characterized by inflammation that presents with erythematous and pruritic skin. Its chronic relapse-remitting nature has a significant impact on the quality of life, and often requires ongoing management. Given the limited treatments available for AD, [...] Read more.
Atopic dermatitis (AD) is a common skin condition characterized by inflammation that presents with erythematous and pruritic skin. Its chronic relapse-remitting nature has a significant impact on the quality of life, and often requires ongoing management. Given the limited treatments available for AD, there remains a large need for effective and safe alternative therapies for long-term use. Janus kinase (JAK) inhibitors are a new class of agents that target the JAK-STAT pathway, which plays an important role in the production of proinflammatory cytokines involved in AD pathogenesis. Phase II and III clinical trials revealed that JAK inhibitors, such as upadacitinib, are effective and well-tolerated agents for the treatment of moderate-to-severe AD. As a result, upadacitinib was approved for use in patients with moderate-to-severe AD by the European Medicines Agency (2021), Health Canada (2021) and the FDA (2022) in the last year. It is important for dermatologists to be aware of the clinical evidence to continue incorporating the use of upadacitinib into the treatment algorithm for AD, which will ultimately lead to improved patient outcomes. Therefore, this review is an up-to-date summary of the clinical data available on the efficacy and safety of upadacitinib treatment for AD. Full article
(This article belongs to the Special Issue New and Emerging Target-Oriented Drugs for Atopic Dermatitis)
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