ArticleJournal of translational medicine2021
Combination of subtherapeutic anti-TNF dose with dasatinib restores clinical and molecular arthritogenic profiles better than standard anti-TNF treatment.
Article in Journal of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- A Rationally Designed Novel Bifunctional Human TNF-α- and Janus Kinase-Targeted soloMER Drug Conjugate (SDC) with a Neutrophil Elastase Cleavable Linker Delivering Inflammation Site-Specific Release of Payload.Journal of medicinal chemistry · 2026Article
- Discovery of potent kinase inhibitors with improved pharmacokinetics and safety potentials through structural optimization of dasatinib.Communications medicine · 2026Article
- Differential Neutrophil and Eosinophil Infiltrations in the Sub-Lining Compartment of Rheumatoid Versus Osteoarthritic Synovium.Mediterranean journal of rheumatology · 2025Article
- Analysis of Cardiovascular Risk Factors in Patients with Psoriasis: A Cross-Sectional Study.Mediterranean journal of rheumatology · 2025Article
- Dasatinib-Loaded Topical Nano-Emulgel for Rheumatoid Arthritis: Formulation Design and Optimization by QbD, In Vitro, Ex Vivo, and In Vivo Evaluation.Pharmaceutics · 2023Article
- The second decade of anti-TNF-a therapy in clinical practice: new lessons and future directions in the COVID-19 era.Rheumatology international · 2022Review
- Case report: JAKi and TNFi dual therapy is a potential treatment strategy for difficult-to-treat rheumatoid arthritis.Frontiers in immunology · 2022Article
- In Silico Identification and Evaluation of Natural Products as Potential Tumor Necrosis Factor Function Inhibitors Using Advanced Enalos Asclepios KNIME Nodes.International journal of molecular sciences · 2021Article
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNew medications for Rheumatoid Arthritis (RA) have emerged in the last decades, including Disease Modifying Antirheumatic Drugs (DMARDs) and biologics. However, there is no known cure, since a significant proportion of patients remain or become non-responders to current therapies. The development of new mode-of-action treatment schemes involving combination therapies could prove successful for the treatment of a greater number of RA patients.
methodsWe investigated the effect of the Tyrosine Kinase inhibitors (TKIs) dasatinib and bosutinib, on the human TNF-dependent Tg197 arthritis mouse model. The inhibitors were administered either as a monotherapy or in combination with a subtherapeutic dose of anti-hTNF biologics and their therapeutic effect was assessed clinically, histopathologically as well as via gene expression analysis and was compared to that of an efficient TNF monotherapy.
resultsDasatinib and, to a lesser extent, bosutinib inhibited the production of TNF and proinflammatory chemokines from arthritogenic synovial fibroblasts. Dasatinib, but not bosutinib, also ameliorated significantly and in a dose-dependent manner both the clinical and histopathological signs of Tg197 arthritis. Combination of dasatinib with a subtherapeutic dose of anti-hTNF biologic agents, resulted in a synergistic inhibitory effect abolishing all arthritis symptoms. Gene expression analysis of whole joint tissue of Tg197 mice revealed that the combination of dasatinib with a low subtherapeutic dose of Infliximab most efficiently restores the pathogenic gene expression profile to that of the healthy state compared to either treatment administered as a monotherapy.
conclusionOur findings show that dasatinib exhibits a therapeutic effect in TNF-driven arthritis and can act in synergy with a subtherapeutic anti-hTNF dose to effectively treat the clinical and histopathological signs of the pathology. The combination of dasatinib and anti-hTNF exhibits a distinct mode of action in restoring the arthritogenic gene signature to that of a healthy profile. Potential clinical applications of combination therapies with kinase inhibitors and anti-TNF agents may provide an interesting alternative to high-dose anti-hTNF monotherapy and increase the number of patients responding to treatment.
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