Current jakinibs for the treatment of rheumatoid arthritis: a systematic review

Rocha, Cláudia Monfroni; Alves, Alessandro Menna; Bettanin, Beatriz Fabris; Majolo, Fernanda; Gehringer, Matthias; Laufer, Stefan; Goettert, Márcia Inês

doi:10.1007/s10787-021-00822-x

Cited by 11 publications

(6 citation statements)

References 19 publications

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“…For safety data, there were 11 deaths reported in tofacitinib and more serious infections in upacitinib. 464 In IBD, all four JAKs are involved in the signal transduction of proinflammatory cytokine, and four JAK transcripts are significantly upregulated in the intestinal mucosa of patients with active ulcerative colitis. 465 Thus, pan-JAK inhibitors may be particularly suitable for treating IBD.…”

Section: Comparisons Between Jak Inhibitorsmentioning

confidence: 99%

The JAK/STAT signaling pathway: from bench to clinic

et al. 2021

Sig Transduct Target Ther

983

623

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The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway was discovered more than a quarter-century ago. As a fulcrum of many vital cellular processes, the JAK/STAT pathway constitutes a rapid membrane-to-nucleus signaling module and induces the expression of various critical mediators of cancer and inflammation. Growing evidence suggests that dysregulation of the JAK/STAT pathway is associated with various cancers and autoimmune diseases. In this review, we discuss the current knowledge about the composition, activation, and regulation of the JAK/STAT pathway. Moreover, we highlight the role of the JAK/STAT pathway and its inhibitors in various diseases.

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Section: Comparisons Between Jak Inhibitorsmentioning

confidence: 99%

The JAK/STAT signaling pathway: from bench to clinic

et al. 2021

Sig Transduct Target Ther

983

623

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“…When comparing upadacitinib to other JAK inhibitors for RA, systematic reviews and meta-analyses demonstrated no significant differences in the safety profiles. 36,38,39,43,[47][48][49][50][51][52][53][54] There were no significant differences observed regarding all cardiovascular events, MACE, OR 0.80 (0.36-1.75), P = 0.57, or venous thromboembolic events (VTE), OR 1.16 (0.48-2.81), P = 0.74, among the JAK inhibitors. 47 There was also no increased risk of VTE with upadacitinib compared with placebo.…”

Section: Meta-analyses and Systematic Reviews Of The Safety Of Jak In...mentioning

confidence: 90%

Upadacitinib for the Treatment of Rheumatoid Arthritis: An Extensive Review

2022

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Objectives: To review the characteristics, efficacy, safety, pharmacoeconomics, and place in therapy of upadacitinib, a Janus kinase (JAK) inhibitor, in the treatment of rheumatoid arthritis (RA). Data Sources: PubMed (January 2003-May 2022) was searched using upadacitinib and ABT-494. Study Selection and Data Extraction: Human studies published in peer-reviewed publications in English were the primary sources for efficacy and safety data. Data Synthesis: In randomized, double-blind, controlled clinical studies, upadacitinib demonstrated statistically significant improvement in RA symptoms as monotherapy and in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) when compared with csDMARD monotherapy or to adalimumab or abatacept in combination with csDMARD therapy in patients with RA. American College of Rheumatology 20% response rates were 68% to 79% for upadacitinib monotherapy and 64% to 84% for upadacitinib plus csDMARD therapy, compared with 28% to 59% for csDMARD-only therapy and 63% to 74% for biologic DMARD (bDMARD) plus csDMARD therapy. Long-term extension studies demonstrated similar findings. Upadacitinib had similar rates of serious infections, herpes zoster, major cardiovascular events, and venous thromboembolic events as other JAK inhibitors. Upadacitinib was similar in cost to tofacitinib and twice as high as baricitinib based on current estimated costs to patients, but actual costs may vary. Relevance to Patient Care and Clinical Practice: Upadacitinib is an alternative therapy to other JAK inhibitors and bDMARDs in patients with moderate to severe RA who have had an inadequate response to a tumor necrosis factor inhibitor alone or in combination with a csDMARD. Conclusions: Upadacitinib is an effective JAK inhibitor for use in RA.

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“…It suggested that leptin might regulate the imbalanced differentiation by JAK2-STAT3 pathway activation and IL-6 secretion. However, the inhibition of JAK had many side effects that limit the clinical application [ 35 ]. In this study, we found that leptin knockdown in RA-FLSs could reverse the hypoxia-mediated reduction of osteogenic differentiation, but attenuated the increase of adipogenic differentiation, which demonstrated the direct effect of leptin in the regulation of the balance of RA-FLS osteogenesis and adipogenesis during hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia Inhibits Osteogenesis and Promotes Adipogenesis of Fibroblast-like Synoviocytes via Upregulation of Leptin in Patients with Rheumatoid Arthritis

Ding

et al. 2022

Journal of Immunology Research

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Hypoxia is associated with the pathogenesis of rheumatoid arthritis (RA). RA fibroblast-like synoviocytes (FLSs) are able to differentiate into osteoblasts and adipocytes. In this study, we aimed to investigate the role of hypoxia in the osteogenesis or adipogenesis of RA-FLSs. Bioinformatics analysis was performed to profile gene expression in the datasets of GSE21959, GSE32006, and GSE55875, and flow cytometry was performed for FLS characterization, while Alizarin Redand Oil Red O staining for osteogenic or adipogenic differentiation of FLSs, respectively. RNA interference leptin knockdown was used to determine the role of leptin in the osteogenesis and adipogenesis of RA-FLSs, and the expression of osteogenic and adipogenic markers was quantified by RT-qPCR and Western blotting. FLSs exhibited a mesenchymal stem cell (MSC)-like phenotype and we observed a limited self-renewal capacity in RA-FLSs compared to that in MSCs, but it was still greater than osteoarthritis (OA)-FLSs. Hypoxia did not change the RA-FLS MSC-like phenotype but inhibited the osteogenic differentiation and promoted the adipogenic differentiation of RA-FLSs. From the bioinformatics analysis ofGSE21959, GSE32006, and GSE55875 datasets, we found leptin, the only perturbed hypoxia-mediated upregulated gene across the three profiled datasets. Leptin knockdown in RA-FLSs reversed the hypoxia-mediated reduction of osteogenesis and hypoxia-mediated enhancement of adipogenesis by elevated expression of osteogenic markers and reduced expression of adipogenic markers, respectively. Therefore, hypoxia-leptin regulation of the osteogenic and adipogenic differentiation of RA-FLSs advances our understanding of RA pathogenesis, meanwhile also provides opportunities for future therapeutic intervention of RA.

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Current jakinibs for the treatment of rheumatoid arthritis: a systematic review

Cited by 11 publications

References 19 publications

The JAK/STAT signaling pathway: from bench to clinic

The JAK/STAT signaling pathway: from bench to clinic

Upadacitinib for the Treatment of Rheumatoid Arthritis: An Extensive Review

Hypoxia Inhibits Osteogenesis and Promotes Adipogenesis of Fibroblast-like Synoviocytes via Upregulation of Leptin in Patients with Rheumatoid Arthritis

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