Immune factors such as interferon‑ɣ and interleukin 4 belong to the group of cytokines that are dependent on type I/II receptors for their signal transmission. Upon activation, these receptors transmit their signal to the cell nucleus and, thus, modulate gene transcription via a signaling cascade consisting of Janus kinases (JAK). This family of four kinases (JAK 1, JAK 2, JAK 3, and tyrosine kinase 2 (TYK2)) subsequently activate members of the signal transducer and activator of transcription (STAT). This finding turned the JAK/STAT signaling pathway into a pharmacological target for the treatment of inflammatory diseases in which cytokines using type I/II receptors play a pathogenic role. In 2018, the European Medicines Agency (EMA) approved tofacitinib for the treatment of psoriatic arthritis. This was the first approval of a JAK/STAT pathway inhibitor for patients treated by dermatologists and rheumatologists. Since then, several new JAK inhibitors have been approved for dermatologic diseases such as atopic dermatitis, alopecia areata, vitiligo, and plaque-type psoriasis. In addition, JAK inhibitors are being investigated for the treatment of many other skin diseases. Thus, systemic JAK inhibitors complete the spectrum of immunotherapeutics with a broader immunological approach compared to monoclonal antibodies. The low molecular weight of JAK inhibitors enables the preparation of these drugs for both systemic and topical administration. Their utilization could represent a valuable alternative to topical steroids. The safety profile of JAK inhibitors must be taken into account. Possible long-term effects may become apparent in the next few years. This article describes both approved JAK inhibitors and relevant new JAK inhibitors that are promising candidates for approval as therapeutics in dermatology.
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http://dx.doi.org/10.1007/s00105-024-05406-8 | DOI Listing |
Ann Rheum Dis
January 2025
School of Medicine, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK; LTHT, NIHR Leeds Biomedical Research Centre, Leeds, UK. Electronic address:
Background: The EULAR recommendations for the treatment of systemic sclerosis (SSc) were updated in 2017, informed by a systematic literature review (SLR) completed in 2014.
Objectives: The aim of this new SLR was to provide the most up-to-date literature to underpin contemporary EULAR recommendations for the management of SSc.
Methods: 30 searches for 30 interventions (including several outcomes/clinical questions), and 1 dedicated search (with several interventions) for calcinosis were prioritised by the task force.
JAAD Int
April 2025
Division of Dermatology, McMaster University, Hamilton, Canada.
Oral Janus kinase inhibitors (JAKi) are increasingly used in dermatology, rheumatology, gastroenterology, and hematology. While effective, they can cause adverse effects such as acne, nausea, cytopenia, dyslipidemia, and Herpes zoster. Recent reports have linked JAKi usage to weight changes, particularly weight gain, which can significantly impact patients' quality of life.
View Article and Find Full Text PDFAutoimmun Rev
January 2025
Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Electronic address:
Tuberculosis (TB), caused by Mycobacterium TB, is the most significant infectious cause of mortality across the globe. While TB disease can prey on immunocompetent individuals, it is more likely to occur in immunocompromised individuals. Immune-mediated inflammatory diseases (IMIDs) are a group of diseases (rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis, psoriasis, hidradenitis suppurative, autoimmune blistering diseases, and others) where there may be a need for systemic immunosuppression to control the disease manifestations, treat symptoms and improve long term outcomes.
View Article and Find Full Text PDFCurr Rheumatol Rep
January 2025
Rheumatologisches Versorgungszentrum Steglitz, Ruhr Universität Bochum, Schloßstr.110, 12163, Berlin, Germany.
Purpose Of Review: Axial spondyloarthritis (axSpA) is a rather prevalent chronic inflammatory rheumatic disease that affects already relatively young patients. It has been known better since the end of the nineteenth century but quite a lot has been learned since the early 60ies when the first classification (diagnostic) criteria for ankylosing spondylitis (AS) were agreed on. I have been part of many developments in the last 30 years, and I'm happy to have been able to contribute to the scientific progress in terms of diagnosis, imaging, pathophysiology and therapy.
View Article and Find Full Text PDFJ Intern Med
January 2025
School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
Background: Evolving evidence suggests that patients undergoing treatment with Janus kinase inhibitors (JAKi) may face an increased risk of cardiovascular events, malignancies, and serious infections.
Objectives: We assessed cardiovascular, malignancy, and serious infection risks associated with JAKi use compared to tumor necrosis factor inhibitor (TNFi) use, which served as the active comparator, in patients with rheumatoid arthritis (RA) or ulcerative colitis (UC).
Methods: This study emulated a target trial using South Korea's nationwide claims database (2013-2023).
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