{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:02:55Z","timestamp":1791464575238,"version":"4.3.4"},"reference-count":219,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,5]],"date-time":"2020-07-05T00:00:00Z","timestamp":1593907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Janus kinase inhibitors (JAKi) belong to a new class of oral targeted disease-modifying drugs which have recently revolutionized the therapeutic panorama of rheumatoid arthritis (RA) and other immune-mediated diseases, placing alongside or even replacing conventional and biological drugs. JAKi are characterized by a novel mechanism of action, consisting of the intracellular interruption of the JAK-STAT pathway crucially involved in the immune response. The aim of this narrative review is to globally report the most relevant pharmacological features and clinical outcomes of the developed and incoming JAKi for RA, based on the available preclinical and clinical evidence. A total of 219 papers, including narrative and systematic reviews, randomized controlled trials (RCTs), observational studies, case reports, guidelines, and drug factsheets, were selected. The efficacy and safety profile of both the first generation JAKi (baricitinib and tofacitinib) and the second generation JAKi (upadacitinib, filgotinib, peficitinib, decernotinib and itacitinib) were compared and discussed. Results from RCTs and real-life data are encouraging and outline a rapid onset of the pharmacologic effects, which are maintained during the time. Their efficacy and safety profile are comparable or superior to those of biologic agents and JAKi proved to be efficacious when given as monotherapy. Finally, the manufacturing of JAKi is relatively easier and cheaper than that of biologics, thus increasing the number of compounds being formulated and tested for clinical use.<\/jats:p>","DOI":"10.3390\/biom10071002","type":"journal-article","created":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T09:49:11Z","timestamp":1594028951000},"page":"1002","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":192,"title":["JAK-Inhibitors for the Treatment of Rheumatoid Arthritis: A Focus on the Present and an Outlook on the Future"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8433-0394","authenticated-orcid":false,"given":"Jacopo","family":"Angelini","sequence":"first","affiliation":[{"name":"Postgraduate School of Clinical Pharmacology and Toxicology, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8426-1395","authenticated-orcid":false,"given":"Rossella","family":"Talotta","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Rheumatology Unit, AOU \u201cGaetano Martino\u201d, University of Messina, 98100 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4219-6182","authenticated-orcid":false,"given":"Rossana","family":"Roncato","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Pordenone, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Fornasier","sequence":"additional","affiliation":[{"name":"Postgraduate School of Clinical Pharmacology and Toxicology, University of Milan, 20133 Milan, Italy"},{"name":"Pharmacy Unit, IRCCS-Burlo Garofolo di Trieste, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Barbiero","sequence":"additional","affiliation":[{"name":"Postgraduate School of Clinical Pharmacology and Toxicology, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Dal Cin","sequence":"additional","affiliation":[{"name":"Postgraduate School of Clinical Pharmacology and Toxicology, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Brancati","sequence":"additional","affiliation":[{"name":"Postgraduate School of Clinical Pharmacology and Toxicology, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8554-2401","authenticated-orcid":false,"given":"Francesco","family":"Scaglione","sequence":"additional","affiliation":[{"name":"Head of Clinical Pharmacology and Toxicology Unit, Grande Ospedale Metropolitano Niguarda, Department of Oncology and Onco-Hematology, Director of Postgraduate School of Clinical Pharmacology and Toxicology, University of Milan, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/msc.152","article-title":"A literature review of the sexual health of women with rheumatoid arthritis","volume":"7","year":"2009","journal-title":"Musculoskelet. 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