The occurrence of acne in patients treated with Janus kinase (JAK) inhibitors for skin diseases is a potential issue, which may reduce treatment adherence. To systematically analyzes randomized clinical trials (RCTs) of JAK inhibitors in dermatological indications for the risk of acne as an adverse event. A meta-analysis of odds ratios (ORs) for acne incidence was conducted. Data were quantitatively synthesized using random-effects meta-analysis. Surface under the cumulative ranking curve (SUCRA) values representing the relative ranking probabilities of treatments were obtained. Analyses were performed using R statistical software version 4.4.0. A total of 11,396 patients were included from 24 studies. The incidence of acne for JAK inhibitors was ranked according to the SUCRA as follows: JAK1 inhibitors > TYK2 inhibitors > combined JAK1 and JAK2 inhibitors > combined JAK1 and TYK2 inhibitors > JAK3 + TEC inhibitors > pan-JAK inhibitors. ORs were higher for longer durations of drug use and larger dosages. Subgroup analyses by disease indication revealed increased ORs for psoriasis (5.52 [95% CI, 1.39-21.88]), vitiligo (4.15 [95% CI, 1.27-13.58]), alopecia areata (3.86 [95% CI, 1.58-9.42]), and atopic dermatitis (2.82 [95% CI, 1.75-4.54]). The use of JAK inhibitors in patients with systemic lupus erythematosus (SLE) may not significantly increase the incidence of acne. There are higher rates of acne following treatment with JAK inhibitors for dermatologic indications, particularly with longer durations and larger dosages. Pan-JAK inhibitors exhibit the lowest incidence of acne.
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http://dx.doi.org/10.1080/09546634.2024.2397477 | DOI Listing |
Elife
December 2024
Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, United States.
Background: Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmunity and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined.
Methods: We report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS, including autoantibody profiling, cytokine analysis, and deep immune mapping.
Front Immunol
December 2024
Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Objectives: Little is known about how various treatments impact the progression of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. Here, we compared ILD progression in RA patients treated with Janus kinase inhibitors (JAKi) or biological disease-modifying anti-rheumatic drugs (bDMARDs). experiments were also performed to evaluate the potential effects of the drugs on epithelial-mesenchymal transition (EMT), a key event in pulmonary fibrosis.
View Article and Find Full Text PDFCell Commun Signal
December 2024
Department of Biomedical Science, Faculty of Medicine, BioMedical Center, University of Iceland, Reykjavík, Iceland.
Background: Melanoma cells frequently dedifferentiate in response to inflammation which can increase responses to certain cytokines. Interferon-γ (IFNγ) is an integral part of the anti-tumor immune response and can directly induce both differentiational changes and expression of immunosuppressive proteins in melanoma cells. How the differentiation status of melanoma cells affects IFNγ responses remains unclear.
View Article and Find Full Text PDFUnited European Gastroenterol J
December 2024
The Sheba Talpiot Medical Leadership Program, Sheba Medical Center, Ramat-Gan, Israel.
Background: Gastrointestinal perforations have been reported in a small number of rheumatoid arthritis (RA) patients treated with Janus kinase (JAK) inhibitors in clinical trials. However, large-scale postmarketing data repositories are needed to further investigate this potentially rare but serious adverse event.
Methods: A retrospective, pharmacovigilance study of the FDA adverse event reporting system (July 2014 to September 2023) assessing the reporting of gastrointestinal perforations following JAK inhibitors compared to biological disease-modifying antirheumatic drugs (bDMARDs) in RA patients.
Oncol Res
December 2024
Department of Pathology, College of Medicine, King Khalid University, Abha, 62521, Saudi Arabia.
Background: Gastric cancer (GC) remains a global health burden and is often characterized by heterogeneous molecular profiles and resistance to conventional therapies. The phosphoinositide 3-kinase and PI3K and Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathways play pivotal roles in GC progression, making them attractive targets for therapeutic interventions.
Methods: This study applied a computational and molecular dynamics simulation approach to identify and characterize SBL-JP-0004 as a potential dual inhibitor of JAK2 and PI3KCD kinases.
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