Objective: One-third of patients with severe rheumatoid arthritis (RA) do not achieve remission or low disease activity, or they have side effects from cDMARD and bDMARD. They will need a new treatment option such as the small molecule JAK inhibitors. In this systematic review, we evaluate the efficacy and safety data of the current jakinibs: tofacitinib, peficitinib, decernotinib, upadacitinib, baricitinib and filgotinib in patients in whom treatment with conventional or biological disease-modifying antirheumatic drugs (cDMARD and/or bDMARD) failed.
Methods: We searched for randomized controlled trials comparing efficacy and safety of jakinibs for RA treatment using the Web of Science, Scopus, PubMed, and clinicaltrials.gov databases with the terms: "rheumatoid arthritis" OR "arthritis rheumatoid" OR "RA" AND "inhibitor" OR "jak inhibitor" AND "clinical trial" OR "treatment" OR "therapy".
Results: All jakinibs achieved good results in ACR 20, 50, 70 and with CRP-DAS28 for LDA and remission, upadacitinib showed better results compared to the others. In ESR-DAS28 for remission, tofacitinib achieved the best result. Regarding the safety of all jakinibs, peficitinib, baricitinib and filgotinib did not register deaths in their studies unlike tofacitinib that presented 11 deaths. Despite all benefits of jakinibs, the use in patients with severe liver and kidney disease should be avoided.
Conclusions: Jakinibs in monotherapy or in combination with methotrexate can be considered a viable alternative in the treatment of moderate-to-severe RA. Even after failures with combination of cDMARDS and bDMARDS, jakinibs demonstrated efficacy.
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http://dx.doi.org/10.1007/s10787-021-00822-x | DOI Listing |
Expert Opin Pharmacother
August 2024
National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Gastroenterol Hepatol (N Y)
December 2023
Department of Gastroenterology, INFINY Institute, FHU-CURE, Nancy University Hospital, and INSERM, Nutrition-Genetics and Environmental Risk Exposure, University of Lorraine, Vandœuvre-lès-Nancy, France.
Ulcerative colitis and Crohn's disease are chronic, progressive inflammatory bowel diseases (IBDs) and are without a known cure. Janus kinase (JAK) is a family of cytosolic tyrosine kinases that mediate signal transduction in response to extracellular stimuli. Abrogating the proinflammatory cytokine signaling cascades using JAK inhibitors (jakinibs) has been shown to be highly effective in the treatment of numerous inflammatory diseases, including IBD.
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February 2024
Grupo de Inmunología Celular e Inmunogenética, Sede de Investigación Universitaria (SIU), Universidad de Antioquia (UDEA), Medellín, Colombia.
Background: Janus kinase inhibitors (jakinibs) are immunomodulators used for treating malignancies, autoimmune diseases, and immunodeficiencies. However, they induce adverse effects such as thrombosis, lymphocytosis, and neutropenia that could be mediated by extracellular vesicles (EVs). These particles are cell membrane-derived structures that transport cellular and environmental molecules and participate in intercellular communication.
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Division of Cardiac Surgery, Department of Surgery, Dalhouise University, Halifax, NS B3H 3A6, Canada.
Diabetes is a chronic illness that can become debilitating owing to its microvascular and macrovascular complications. Its prevalence is increasing and so is its cost. Diabetes, particularly type 2, appears to have a very close relationship with obesity.
View Article and Find Full Text PDFAnn Rheum Dis
January 2024
Translational 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.
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