Cláudia Monfroni Rocha1, Alessandro Menna Alves2, Beatriz Fabris Bettanin1,2, Fernanda Majolo1, Matthias Gehringer3,4, Stefan Laufer5,3,4, Márcia Inês Goettert6,7. 1. Cell Culture Laboratory, Biotechnology Graduate Program, Universidade do Vale do Taquari, Univates, Av. Avelino Talini, 171, Lajeado, RS, 95914-014, Brazil. 2. School of Dentistry, University Center Univates, Lajeado, RS, Brazil. 3. Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', Eberhard Karls Universität Tübingen, Tübingen, Germany. 4. Tübingen Center for Academic Drug Discovery (TüCAD2), Tübingen, Germany. 5. Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Eberhard Karls Universität Tübingen, Tübingen, Germany. 6. Cell Culture Laboratory, Biotechnology Graduate Program, Universidade do Vale do Taquari, Univates, Av. Avelino Talini, 171, Lajeado, RS, 95914-014, Brazil. marcia.goettert@univates.br. 7. Medical Sciences Graduate Program, Universidade do Vale do Taquari, Univates, Lajeado, Brazil. marcia.goettert@univates.br.
Abstract
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.
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.
Entities:
Keywords:
JAK inhibitors; Rheumatoid arthritis; Small molecules
Authors: Pedro Santos-Moreno; Susan Martinez; Linda Ibata; Laura Villarreal; Fernando Rodríguez-Florido; Manuel Rivero; Adriana Rojas-Villarraga; Claudio Galarza-Maldonado Journal: Biologics Date: 2022-07-13