Dataset Information

Treatment of Atopic Dermatitis with Biologic Drugs.

ABSTRACT: Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease which predominately affects children and usually clears up during infancy or childhood. However, AD may persist with a chronic relapsing course until adulthood or develop at a later age. AD treatment can often be complicated. Treating moderate-to-severe AD can be challenging: only a few therapeutic options are available, with cyclosporine being the only approved and labeled systemic drug. In the last few years, advances in the knowledge of AD pathogenesis have been made that can provide the basis for developing new topical and systemic drugs. Among them, biologic drugs targeting specific cytokines involved in the development of the disease will probably revolutionize AD therapy. Currently, dupilumab, a monoclonal antibody that binds to the shared alpha chain subunit of the receptors for IL-4 and IL-13, is the only biologic drug licensed for the treatment of AD in adults. However, other biologic drugs that selectively target some key cytokines in AD pathogenesis (IL-13, IL-31, and IL-22) are also being studied. In this review, we discuss all of the biologic drugs that have been studied for AD treatment.

SUBMITTER: Fabbrocini G

PROVIDER: S-EPMC6261117 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Treatment of Atopic Dermatitis with Biologic Drugs.

Fabbrocini Gabriella G Napolitano Maddalena M Megna Matteo M Balato Nicola N Patruno Cataldo C

Dermatology and therapy 20180904 4

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease which predominately affects children and usually clears up during infancy or childhood. However, AD may persist with a chronic relapsing course until adulthood or develop at a later age. AD treatment can often be complicated. Treating moderate-to-severe AD can be challenging: only a few therapeutic options are available, with cyclosporine being the only approved and labeled systemic drug. In the last few years, advances in ...[more]

PMID: 30182182

Similar Datasets

Project description:IntroductionAtopic dermatitis (AD) is a genetically based chronic inflammatory dermatosis associated with multiple triggers and complex pathophysiological mechanisms. Nowadays, an authentic therapeutic revolution is taking place with the incorporation of biological drugs for the treatment of moderate and severe atopic dermatitis. A new systematic revision (RS) is necessary to support decision-making for specialists treating AD.MethodsA literature search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials was performed between 1 January 2000 and 30 April 2022. Phase III randomized clinical trials (RCTs) of EMA-approved molecules were included. The main variables analyzed were a 75% improvement in the Eczema Area and Severity Index (EASI 75) and the number of patients who reached 0 in the Investigator Global Assessment (IGA) (fully cleared patients) or IGA 1 (almost cleared patients) at the end of the study period (week 48-60). The risk of bias was analyzed with the Cochrane Risk of Bias Assessment (ROB-2) tool, focused on the primary objectives. Before carrying out the study, the protocol was registered in PROSPERO with the number CRD42022331109.ResultsA total of 3299 studies were systematically identified via databases and registers (442 from PubMed/MEDLINE, 2857 from Embase and 719 from CENTRAL). Finally, five publications containing seven RCTs were included in the final sample of detailed data extraction and data analyses. Regarding efficacy, the best results are obtained with Upadacitinib 30 mg (84.7% (77.3-92.1)) at 52 weeks, slightly improving its results when TCS is added (84.9% (80.3-89.5)). These results are replicated in the measurement of vIGA 0/1 for Updacitinib 30 mg + TCS, where 65.5% (55.7-75.2) of patients maintain it at 52 weeks. Of the four drugs, no long-term safety results have been reported for baricitinib. In relation to the safety findings, there were no significant differences in the dropout rates for this reason in the remaining three drugs.DiscussionToday, different therapeutic options for AD patients can be prescribed. Individualizing the treatment allows for better therapeutic consistency, in addition to being cost-efficient to avoid primary therapeutic failures. The results of the present SR may provide us with a useful basis for the preparation of management guidelines for the use of new generation therapies in moderate to severe atopic dermatitis.

Project description:BackgroundAtopic dermatitis (AD) is a prevalent chronic inflammatory skin disease whose pathophysiology involves the interplay between genetic and environmental factors, ultimately leading to dysfunction of the epidermis. While several treatments are effective in symptom management, many existing therapies offer only temporary relief and often come with side effects. For this reason, the formulation of an effective therapeutic plan is challenging and there is a need for more effective and targeted treatments that address the root causes of the condition. Here, we hypothesise that modelling the complexity of the molecular buildup of the atopic dermatitis can be a concrete means to drive drug discovery.MethodsWe preprocessed, harmonised and integrated publicly available transcriptomics datasets of lesional and non-lesional skin from AD patients. We inferred co-expression network models of both AD lesional and non-lesional skin and exploited their interactional properties by integrating them with a priori knowledge in order to extrapolate a robust AD disease module. Pharmacophore-based virtual screening was then utilised to build a tailored library of compounds potentially active for AD.ResultsIn this study, we identified a core disease module for AD, pinpointing known and unknown molecular determinants underlying the skin lesions. We identified skin- and immune-cell type signatures expressed by the disease module, and characterised the impaired cellular functions underlying the complex phenotype of atopic dermatitis. Therefore, by investigating the connectivity of genes belonging to the AD module, we prioritised novel putative biomarkers of the disease. Finally, we defined a tailored compound library by characterising the therapeutic potential of drugs targeting genes within the disease module to facilitate and tailor future drug discovery efforts towards novel pharmacological strategies for AD.ConclusionsOverall, our study reveals a core disease module providing unprecedented information about genetic, transcriptional and pharmacological relationships that foster drug discovery in atopic dermatitis.

Project description:Biologic therapies are increasingly used to treat chronic inflammatory skin diseases such as psoriasis and atopic dermatitis. In clinical practice, scores based on evaluation of objective and subjective symptoms are used to assess disease severity, leading to evaluation of treatment goals with clinical decisions on treatment initiation, switch to another treatment modality or to discontinue current treatment. However, this visual-based scoring is relatively subjective and inaccurate due to inter- and intraobserver reliability. Optical coherence tomography (OCT) is a fast, high-resolution, in vivo imaging modality that enables the visualization of skin structure and vasculature. We evaluated the use of OCT for quantification and monitoring of skin inflammation to improve objective assessment of disease activity in patients with psoriasis and atopic dermatitis. We assessed the following imaging parameters including epidermal thickness, vascular density, plexus depth, vessel diameter, and vessel count. A total of four patients with psoriasis or atopic dermatitis were treated with biologic agents according to current treatment guidelines. OCT was used to monitor their individual treatment response in a target lesion representing disease activity for 52 weeks. Psoriatic and eczema lesions exhibited higher epidermal thickness, increased vascular density, and higher vessel count compared to uninvolved skin. An upward shift of the superficial vascular plexus accompanied by smaller vessel diameters was seen in psoriasis in contrast to atopic dermatitis, where larger vessels were observed. A response to biologic therapy was characterized by normalization of the imaging parameters in the target lesions in comparison to uninvolved skin during the observation period of 52 weeks. Optical coherence tomography potentially serves as an instrument to monitor biologic therapy in inflammatory skin diseases. Imaging parameters may enable objective quantification of inflammation in psoriasis or atopic dermatitis in selected representative skin areas. OCT may reveal persistent subclinical inflammation in atopic dermatitis beyond clinical remission.

Dataset Information

Treatment of Atopic Dermatitis with Biologic Drugs.

Publications

Treatment of Atopic Dermatitis with Biologic Drugs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets