Treatment of Atopic Dermatitis with Biologic Drugs.
Ontology highlight
ABSTRACT:
SUBMITTER: Fabbrocini G
PROVIDER: S-EPMC6261117 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
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.
| S-EPMC10792836 | biostudies-literature
Project description:Therapeutic regimens for the treatment and long-term management of AD traditionally had a two-fold objective of decreasing skin inflammation and repairing the defective skin barrier. Essential treatments for AD in children should include topical moisturizers for skin hydration and prevention of flares, topical anti-inflammatory medications (e.g. corticosteroids, calcineurin inhibitors, PDE4 inhibitor), allergen/irritant avoidance, and treatment of skin infections. Treatment regimens should be severity-based, and implemented in a stepwise approach tailored to the individual patient. This stepwise approach includes initial use of emollients, gentle skin care, and escalating to more potent anti-inflammatory treatments as the disease severity increases. Currently available systemic medications should be reserved for the presence of recalcitrance to topical therapies due to associated toxicities. We believe that early treatment of AD is not only essential in treating the skin disease, but also in preventing the development of additional atopic diseases, such as food allergy, asthma and allergic rhinitis. The defective skin barrier of AD permits a route of entry for food and environmental allergens, and upon exposure, keratinocytes secrete TSLP, which activates the TH2 pathway. This TH2 differentiation sets off the atopic march and the subsequent diseases that are seen. This review highlights treatment options and strategies in pediatric AD therapy with an emphasis on early therapy. Supporting evidence on the efficacy and safety of each intervention will be discussed.
| S-EPMC5983898 | biostudies-literature
Project description:Atopic dermatitis (AD) is a common chronic relapsing inflammatory skin disease. The pathogenesis of AD is complex and still not fully understood. Despite recent therapeutic developments, the current therapeutic arsenal of AD remains limited and is associated with long-term efficacy and safety issues. Therefore, new topical therapies with different mechanisms of action are required to overcome the limitations of existing treatments. Difamilast is a phosphodiesterase 4 inhibitor currently in phase 3 studies. Difamilast shows antipruritic and anti-inflammatory properties and a rapid onset of action, with significant differences in some parameters from the vehicle within 1 week of treatment. Phase 2 and 3 clinical trials have shown that difamilast ointments are effective and well tolerated in adult and pediatric patients with AD, and are expected to be used for long-term AD treatment. In 2021, difamilast was the first phosphodiesterase 4inhibitor to acquire manufacturing and marketing approval in Japan for the treatment of adult and pediatric patients (2 years of age and older) with AD. This article is a narrative review of the current literature on difamilast in the management of AD.
| S-EPMC10328024 | 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:PurposeManagement of atopic dermatitis (AD) typically requires application of topical treatments, often multiple times a day. The cosmetic properties and burdensome application of these treatments can be detrimental to quality of life (QoL). Patients who achieve good disease control through use of systemic therapies may reduce the frequency and amount of topical applications, improving QoL. This study aimed to quantify the utility and disutility for topical AD treatment processes.MethodsSeven vignettes describing different skincare regimens for people with moderate-to-severe AD were developed with input from healthcare professionals. 484 respondents from the general population completed time trade-off items for each vignette. Utility values for each regimen, and disutilities associated with the impact of changes to skincare regimens, were calculated. Analysis of variance assessed differences between skincare regimens.ResultsAs skincare regimens increased in intensity (0.7968 for the most intense; 0.9999 for the least), utility values decreased. There were no statistically significant differences between skincare regimens followed by patients with good disease control (0.9862 to 0.9999); however, when compared to those involving topical corticosteroids and emollient combinations (0.7968 to 0.8835), significant differences were observed (p?<?0.001). The largest disutilities (0.1521 to 0.1705) were between skincare regimens describing the use of topical corticosteroids plus emollient and those followed by patients with good disease control.ConclusionsThe application of topical treatments has a detrimental effect on QoL, which increases with the duration and frequency of applications. Further research is needed to investigate how health and process utilities interact and both can be integrated into medical decision-making.
| S-EPMC6698259 | biostudies-literature
Project description:Globally, the prevalence of Atopic dermatitis (AD) is significantly increasing and affecting around 20% of population including children. Complex interactions amongst abnormality in epidermal barrier function, environment, infectious agents and immunological defects are considered as key factors in the pathogenesis of AD. Although the role of oxidative stress has been studied in some skin diseases, investigation of the same in AD is intermittent. Calcineurin inhibitors and/or topical corticosteroids are currently available; however, it causes atrophy of the skin, burning sensation, and systemic side effects which leads to poor patient compliance. These limitations provoke the strong need to develop an innovative approach in managing AD. Nanomaterials for effective drug delivery to skin conditions such as AD have attracted a lot of attention owing to its ability to encapsulate, protect, and release the cargo at the diseased skin site. However, there are lots of unmet challenges especially in terms of development of non-toxic formulations and clinical translation of established nanomedicines in the form of accessible products. Numerous formulations have emerged as carrier for poorly soluble and permeable drugs, viz., lipidic, polymeric, metal, silica, liposomes, hydrocarbon gels and this field is evolving. This review is intended to provide an insight incidences associated with pathophysiology of AD and challenges with existing treatments of AD. Focus is kept on reviewing current development and emerging nanomedicines for effective treatment of AD. The review also inculcates merits of several nanomedicines in overcoming challenges of existing products and its future implications.
| S-EPMC7828097 | biostudies-literature
Project description:BackgroundIn 2015, the Korean Atopic Dermatitis Association (KADA) working group published consensus guidelines for treating atopic dermatitis (AD).ObjectiveWe aimed to provide updated consensus recommendations for systemic treatment of AD in South Korea based on recent evidence and experience.MethodsWe compiled a database of references from relevant systematic reviews and guidelines on the systemic management of AD. Evidence for each statement was graded and classified based on thestrength of the recommendation. Forty-two council members from the KADA participated in three rounds of voting to establish a consensus on expert recommendations.ResultsWe do not recommend long-term treatment with systemic steroids forpatients with moderate-to-severe AD due to the risk of adverse effects. We recommend treatment with cyclosporine or dupilumab and selective treatment with methotrexate or azathioprine for patients with moderate-to-severe AD. We suggest treatment with antihistamines as an option for alleviating clinical symptoms of AD. We recommend selective treatment with narrowband ultraviolet B for patients with chronic moderate-to-severe AD. We do not recommend treatment with oral antibiotics for patients with moderate-to-severe AD but who have no signs of infection. We did not reach a consensus on recommendations for treatment with allergen-specific immunotherapy, probiotics, evening primrose oil, orvitamin D for patients with moderate-to-severe AD. We also recommend educational interventions and counselling for patients with AD and caregivers to improve the treatment success rate.ConclusionWe look forward to implementing a new and updated consensus of systemic therapy in controlling patients with moderate-to-severe AD.
| S-EPMC8577915 | biostudies-literature
Project description:Atopic dermatitis (AD) is a chronic and relapsing disease affecting an increasing number of patients. Usually starting in early childhood, AD can be the initial step of the so-called atopic march, i.e. followed by allergic rhinitis and allergic asthma. AD is a paradigmatic genetically complex disease involving gene-gene and gene-environment interactions. Genetic linkage analysis as well as association studies have identified several candidate genes linked to either the epidermal barrier function or to the immune system. Stress, bacterial or viral infections, the exposure to aero- or food-allergens as well as hygienic factors are discussed to aggravate symptoms of AD. Athough generalized Th2-deviated immune response is closely linked to the condition of AD, the skin disease itself is a biphasic inflammation with an initial Th2 phase and while chronic lesions harbour Th0/Th1 cells. Regulatory T cells have been shown to be altered in AD as well as the innate immune system in the skin. The main treatment-goals include the elimination of inflammation and infection, preserving and restoring the barrier function and controlling exacerbating factors. The overall future strategy in AD will be aimed to control skin inflammation by a more proactive management in order to potentially prevent the emergence of sensitization as well as to design customized management based on genetic and pathophysiologic information.
| S-EPMC2883413 | biostudies-literature
Project description:Objective: To review the efficacy and safety of crisaborole and its place in therapy for the management of mild to moderate atopic dermatitis (AD). Data Sources: A literature search of PubMed (data inception to February 2019) was performed using the search terms crisaborole and atopic dermatitis. Supplementary sources included the Journal of the American Academy of Dermatology Guidelines of Care for the Management of Atopic Dermatitis, clinicaltrials.gov data, manufacturer prescribing information, and article bibliographies. Study Selection and Data Extraction: Relevant English-language studies and those conducted in humans were considered and reviewed. Abstracts from clinical trials and drug reviews were reviewed. Phases I, II, III, and long-term safety studies were included. Data Synthesis: Data from multiple clinical trials have demonstrated the effectiveness and safety of crisaborole topical ointment. Patients treated with crisaborole experienced improvement in AD symptoms based on improvement in the Investigator’s Static Global Assessment and the AD Severity Index scores. Crisaborole has a limited adverse event profile and low systemic absorption. Relevance to Patient Care and Clinical Practice: Crisaborole is the first topical phosphodiesterase 4 inhibitor indicated for the treatment of mild to moderate AD. Its place in therapy is along with topical calcineurin inhibitors as a second-line option for patients who are recalcitrant to or unable to use topical corticosteroids. Conclusions: Crisaborole is a safe and efficacious second-line option for the treatment of mild to moderate AD in patients 2 years of age and older.
| S-EPMC6600556 | biostudies-literature
Project description:Atopic dermatitis (AD) is the most common atopic disease in young children and most common skin disease in childhood. In the Polish population, the incidence of AD in the group of children aged 6-14 is about 4% and it is underestimated. The disease is chronic and recurrent, and the leading symptom is skin pruritus that in the mechanism of the vicious circle is accompanied by scratching that causes generalized infections. The overall problems lead to a decrease in the quality of life of the child and its parents and to an increased risk of psychosomatic diseases. The complex pathomechanism of AD is due to chronic inflammation of the skin, in which various cell phenotypes are involved. The management is comprehensive and it is aimed at reducing inflammation, improving the skin barrier function, reducing the symptoms of dryness and itching of the skin and secondarily improving the quality of life. The treatment includes intensive skincare, anti-inflammatory treatment based on the proactive use of topical glucocorticosteroids and topical calcineurin inhibitors. Periods of exacerbation of lesions require intensified treatment. In particularly severe, recurrent cases, treatment options can be extended to systemic immunosuppressive drugs, with awareness of their adverse effects. Previous year has brought significant progress in the current treatment of AD in the form of biological treatment. Cytokines and other mediators that play an important role in the pathogenesis of skin inflammation have become a target for new forms of therapy. Drugs for which interleukin (IL)-4 and IL-13 are the targets are particularly represented. Dupilumab is the first biological drug approved for the general treatment of children aged >12 years with moderate to severe AD. Another therapeutic option for topical use is crisaborole, a phosphodiesterase-4 inhibitor. This study presents the current state of research on biological drugs in AD.
| S-EPMC8518108 | biostudies-literature