Selectivity, efficacy and safety of JAKinibs: new evidence for a still evolving story

Ann Rheum Dis. 2024 Jan 11;83(2):139-160. doi: 10.1136/ard-2023-223850.


Michael Bonelli 1Andreas Kerschbaumer 2Kastriot Kastrati 2Kamran Ghoreschi 3Massimo Gadina 4Leonhard X Heinz 2Josef S Smolen 2Daniel Aletaha 2John O'Shea 4Arian Laurence 5


Author information

1Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria michael.bonelli@meduniwien.ac.at.

2Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

3Department of Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.

4Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.

5Translational Gastroenterology Unit, Department of Haematology, University College Hospital, UCLH Hospitals NHS Trust, University of Oxford, Oxford, UK.


Fundamental insight gained over the last decades led to the discovery of cytokines as pivotal drivers of inflammatory diseases such as rheumatoid arthritis, psoriasis/psoriasis arthritis, inflammatory bowel diseases, atopic dermatitis and spondylarthritis. A deeper understanding of the pro-inflammatory and anti-inflammatory effects of various cytokines has prompted new cytokine-targeting therapies, which revolutionised the treatment options in the last years for patients with inflammatory disorders. Disease-associated immune responses typically involve a complex interplay of multiple cytokines. Therefore, blockade of one single cytokine does not necessarily lead to a persistent remission in all patients with inflammatory disorders and fostered new therapeutic strategies targeting intracellular pathways shared by multiple cytokines. By inhibiting JAK-STAT signalling pathways common to families of cytokines, JAK-inhibitors (JAKinibs) have created a new paradigm for the treatment of inflammatory diseases. Multiple agents have been approved for various disorders and more are being investigated for several new indications. Second-generation selective JAKinibs have been devised with the aim to achieve an increased selectivity and a possible reduced risk of side effects. In the current review, we will summarise the current body of evidence of pan versus selective JAKinibs and the most recent insights on new side effects and indications, including COVID-19.

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