Comparative efficacy of biologics and small molecule drugs in treating pediatric atopic dermatitis in patients aged 2–18 years: A 12–16 week network meta‐analysis of randomized controlled trials

Pediatric Allergy and Immunology, Journal Year: 2025, Volume and Issue: 36(2)

Published: Feb. 1, 2025

Atopic dermatitis (AD) predominantly manifests before age five, with significant phenotype variations across groups. Despite increasing systemic treatments for pediatric AD, head-to-head comparisons in network meta-analyses focused on children are scarce. Through systematic searches of PubMed, Embase, Web Science, and Cochrane Library up to March 2024, we identified randomized controlled trials (RCTs) evaluating moderate-to-severe AD aged 2-18 years. From 900 screened articles, 8 RCTs (n = 2636) met inclusion criteria, comparing dupilumab, baricitinib, upadacitinib, abrocitinib versus placebo standard care. Primary outcome was Eczema Area Severity Index (EASI) scores at 12-16 weeks. Upadacitinib demonstrated highest efficacy both 30 mg (risk difference [RD] 0.62 [0.53, 0.71]) 15 (RD 0.52 [0.42, 0.62]). Dupilumab (weight-based dosing corticosteroids; RD 0.43 [0.29, 0.57]), (200 mg; 0.40 0.50]; 100 0.30 [0.20, 0.41]), baricitinib (4 0.21 [0.06, 0.35]) also showed over placebo. This analysis establishes a hierarchy effectiveness among therapies upadacitinib showing efficacy. However, the predominance adolescent data emphasizes need age-stratified studies younger long-term safety assessments.

Language: Английский

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Off-Label Treatment in Inflammatory Skin Diseases—European Point of View

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(7), P. 2376 - 2376

Published: March 30, 2025

Off-label treatment is the use of a drug approved for marketing, outside registration in terms indication, age group, dose or route administration. Despite constant appearance new preparations on market, SmPCs guidelines current clinical problem. It believed that it based needs patients unmet by classical therapy methods. This work focuses off-label inflammatory dermatoses such as atopic dermatitis, psoriasis, acne vulgaris and rosacea. Publications this subject, available PubMed, Google Scholar Cochrane Library, were analyzed form review, taking into account mechanisms action, efficacy safety preparations. Based literature analysis, can be concluded drugs SmPC indications common situation dermatology. However, difficult to determine its exact frequency-there lack data prevalence appliances from European perspective. demonstrate varying effectiveness therapy, depending specific preparation. dermatology remains an important issue should explored further research.

Language: Английский

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Discovery and Optimization of Potent and Highly Selective PARP14 Inhibitors for the Treatment of Atopic Dermatitis

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Atopic dermatitis (AD) is a chronic, recurrent, and inflammatory skin condition that remains challenging to treat effectively safely with current therapies. Recent studies by multiple independent research groups have demonstrated poly(ADP-ribose) polymerase 14 (PARP14) has been implicated in the progression of diseases through its regulation Th2 Th17 signaling pathways, leading identification PARP14 as promising therapeutic target. Herein, we report discovery novel inhibitor Q22 exceptional inhibitory activity against (IC50 = 5.52 nM), high selectivity toward PARP14, favorable pharmacokinetic properties, robust vivo safety profile. Notably, compared positive control RBN-3143, showed significant efficacy dinitrochlorobenzene (DNCB)-induced AD mouse model markedly reducing expression key AD-associated cytokines, including IL-4, IL-13, IL-17A. These findings suggest holds considerable promise for treatment.

Language: Английский

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JAK-ing up chronic actinic dermatitis with upadacitinib

Clinical and Experimental Dermatology, Journal Year: 2023, Volume and Issue: 49(2), P. 173 - 175

Published: Oct. 13, 2023

We describe a unique and significant case of 75-year-old man successfully treated with upadacitinib for chronic actinic dermatitis.

Language: Английский

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Nonsteroidal Approaches for Atopic Dermatitis: A Clinical Update

Dermatitis, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 6, 2024

Abstract: Topical corticosteroids (TCSs) are the most widely used treatment for atopic dermatitis (AD), but they can have adverse effects such as skin atrophy, telangiectasias, and hypopigmentation, especially with prolonged use of higher potency steroids. Many patients also a fear using TCSs, known "corticophobia." With development biologics Janus kinase inhibitors, nonsteroidal approach to AD may be possible preferred by certain patients. Given what is about these therapies, we propose structured ladder action plan that guide clinicians on therapies AD. The divides medication classes into treatments exacerbation versus maintenance in an escalating order increasing potential effects, both real perceived. This algorithm proposal paves way managing

Language: Английский

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Tissue gene expression profiles and communication networks inform candidate blood biomarker identification in psoriasis and atopic dermatitis

Clinical Immunology, Journal Year: 2024, Volume and Issue: 265, P. 110283 - 110283

Published: June 15, 2024

Overlapping clinical and pathomechanistic features can complicate the diagnosis treatment of inflammatory skin diseases, including psoriasis atopic dermatitis (AD). Spatial transcriptomics allows identification disease- cell-specific molecular signatures that may advance biomarker development future treatments. This study identified transcriptional in keratinocytes sub-basal CD4+ CD8+ T lymphocytes from patients with AD. In silico prediction ligand:receptor interactions delivered key signalling pathways (interferon, effector cells, stroma cell matrix biology, neuronal development, etc.). Targeted validation selected transcripts, CCL22, RELB, JUND, peripheral blood cells suggests chosen approach as a promising tool also other diseases. Psoriasis AD are characterized by dysregulation be targeted therapeutically. is valuable search for used biomarkers and/or therapeutic targets.

Language: Английский

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Cytotoxic and Immunomodulatory Effects of Hypericin as a Photosensitizer in Photodynamic Therapy Used on Skin Cell Cultures

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(6), P. 696 - 696

Published: May 23, 2024

Determination of the hypericin–photodynamic (HY–PDT) effect on secretion cytokines secreted by skin cells, may be basis for using immunomodulatory photodynamic action in treatment inflammatory diseases. The study aimed to evaluate cytotoxic and effects hypericin (HY) therapy (PDT) performed vitro cultures selected cell lines. used two human lines, primary dermal fibroblast (HDFa) epidermal keratinocytes (HEKa). MTT test was define metabolic activity treated cells. Cell supernatants subjected sublethal PDT were assessed determine interleukins: IL-2, IL-8, IL-10, IL-11, IL-19, IL-22, metalloproteinase 1 (MMP-1). results confirm destructive HY–PDT doses depending concentration HY light doses. No statistically significant differences noted IL-2 IL-10 after HEKa HDFa After HY–PDT, MMP-1, IL-11 significantly decreased line. Moreover, IL-19 MMP-1 line only HY, without light, increased but HY–PDT. Our experiment confirmed that has not a but, doses, also presents properties. These an advantage when persistent inflammation, connected with release pro-inflammatory resistant conventional methods.

Language: Английский

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A Case Report of JAK Inhibitors Therapy for Adult-Onset Still’s Disease with Persistent Pruritic Lesions

Drugs in R&D, Journal Year: 2024, Volume and Issue: 24(3), P. 391 - 394

Published: Sept. 1, 2024

Adult-onset Still's disease (AOSD) is a recognized autoinflammatory disorder of unknown etiology. The standard initial management for AOSD includes conventional corticosteroids and disease-modifying antirheumatic drugs. In cases that are resistant to these treatments, additional therapeutic options such as immunosuppressants, biologics, other alternative treatments may be considered. Yet, significant proportion patients remain unresponsive interventions. Herein, case reported involving patient with who had persistent pruritic lesions did not respond therapy, but were alleviated Janus kinase inhibitors (JAKi), namely baricitinib upadacitinib. objective expand the number refractory treated JAKi in clinical practice. Another aim offer potentially effective experience pruritus.

Language: Английский

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Amenorrhea in an Adolescent Female as a Rare Adverse Event of Upadacitinib Treatment for Atopic Dermatitis

Patient Preference and Adherence, Journal Year: 2024, Volume and Issue: Volume 18, P. 2307 - 2310

Published: Nov. 1, 2024

Atopic dermatitis (AD) is a common chronic inflammatory cutaneous disease. Upadacitinib, selective JAK-1 inhibitor, has been approved as systemic medication for moderate-to-severe AD in patients aged ≥12 years. Although previous studies have examined the safety profile of upadacitinib, this first report to describe potential association between amenorrhea and upadacitinib or other JAK inhibitors. Herein, we rare adverse event an adolescent female patient who was treated with AD. This case expands range events potentially associated therapy.

Language: Английский

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Upadacitinib for the Treatment of Moderate-to-Severe Crohn’s Disease

Immunotherapy, Journal Year: 2024, Volume and Issue: 16(6), P. 345 - 357

Published: Feb. 16, 2024

Despite an increasing number of therapies for Crohn's disease (CD), half patients do not respond to initial treatment or lose response over time, highlighting the need novel therapies. Inhibition Janus kinases (JAKs) has emerged as important therapeutic target CD. Upadacitinib is orally administered selective JAK1 inhibitor, which effective induction and maintenance remission in moderately-to-severely active CD, including with prior failure biological therapy. Nonselective JAK inhibition been associated thromboembolic disease, cardiovascular events malignancy older than 50 years rheumatoid arthritis pre-existing risk factors, should be considered upon prescription. first currently only oral advanced therapy

Language: Английский

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