ArticleArthritis research & therapy2021
Application of systems biology-based in silico tools to optimize treatment strategy identification in Still's disease.
Article in Arthritis research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Early intensification versus step-up biologic strategies in systemic juvenile idiopathic arthritis: a Bayesian network meta-analysis of remission and safety outcomes.Pediatric rheumatology online journal · 2026Pooled it
- Effectiveness of Canakinumab for First-Line Steroid-Free Treatment in Systemic-Onset Juvenile Idiopathic Arthritis and Juvenile Still Disease.ACR open rheumatology · 2026Article
- In silico analysis of atrial fibrillation and hypertension mechanism of action secondary to ibrutinib/acalabrutinib in chronic lymphocytic leukemia.Scientific reports · 2025Article
- Closed circuit artificial ıntelligence model named morgaf for childhood onset systemic lupus erythematosus diagnosis.Scientific reports · 2025Article
- Digital patient modeling identifies predictive biomarkers of regorafenib response in elderly metastatic colorectal cancer.Frontiers in systems biology · 2025Article
- Synergistic effects of vedolizumab and JAK 1,2,3 inhibitors in Crohn's disease: insights from a systems biology and artificial intelligence-based approach.Frontiers in immunology · 2025Article
- Innate immunity of bile and cholangiocytes in primary biliary cholangitis.Frontiers in immunology · 2025Review
- The emerging paradigm in pediatric rheumatology: harnessing the power of artificial intelligence.Rheumatology international · 2024Review
- In Silico Modeling of Fabry Disease Pathophysiology for the Identification of Early Cellular Damage Biomarker Candidates.International journal of molecular sciences · 2024Article
- Machine Learning-Driven Biomarker Discovery for Skeletal Complications in Type 1 Gaucher Disease Patients.International journal of molecular sciences · 2024Article
- Aflibercept Off-Target Effects in Diabetic Macular Edema: An In Silico Modeling Approach.International journal of molecular sciences · 2024Article
- Application of systems biology to identify pharmacological mechanisms of thrombotic microangiopathy evoked by combined activated prothrombin complex concentrate and emicizumab.Scientific reports · 2023Article
- A quantitative systems pharmacology model for certolizumab pegol treatment in moderate-to-severe psoriasis.Frontiers in immunology · 2023Article
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- The circadian rhythm: an influential soundtrack in the diabetes story.Frontiers in endocrinology · 2023Review
- Article
- Identification of the Potential Molecular Mechanisms Linking RUNX1 Activity with Nonalcoholic Fatty Liver Disease, by Means of Systems Biology.Biomedicines · 2022Article
- Identification of Potential Muscle Biomarkers in McArdle Disease: Insights from Muscle Proteome Analysis.International journal of molecular sciences · 2022Article
- Strategy and Challenges of Paraclinical Examinations in Adult-Onset Still's Disease.Journal of clinical medicine · 2022Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSystemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD) are manifestations of an autoinflammatory disorder with complex pathophysiology and significant morbidity, together also termed Still's disease. The objective of the current study is to set in silico models based on systems biology and investigate the optimal treat-to-target strategy for Still's disease as a proof-of-concept of the modeling approach.
methodsMolecular characteristics of Still's disease and data on biological inhibitors of interleukin (IL)-1 (anakinra, canakinumab), IL-6 (tocilizumab, sarilumab), and glucocorticoids as well as conventional disease-modifying anti-rheumatic drugs (DMARDs, methotrexate) were used to construct in silico mechanisms of action (MoA) models by means of Therapeutic Performance Mapping System (TPMS) technology. TPMS combines artificial neuronal networks, sampling-based methods, and artificial intelligence. Model outcomes were validated with published expression data from sJIA patients.
resultsBiologicals demonstrated more pathophysiology-directed efficiency than non-biological drugs. IL-1 blockade mainly acts on proteins implicated in the innate immune system, while IL-6 signaling blockade has a weaker effect on innate immunity and rather affects adaptive immune mechanisms. The MoA models showed that in the autoinflammatory/systemic phases of Still's disease, in which the innate immunity plays a pivotal role, the IL-1β-neutralizing antibody canakinumab is more efficient than the IL-6 receptor-inhibiting antibody tocilizumab. MoA models reproduced 67% of the information obtained from expression data.
conclusionsSystems biology-based modeling supported the preferred use of biologics as an immunomodulatory treatment strategy for Still's disease. Our results reinforce the role for IL-1 blockade on innate immunity regulation, which is critical in systemic autoinflammatory diseases. This further encourages early use on Still's disease IL-1 blockade to prevent the development of disease or drug-related complications. Further analysis at the clinical level will validate the findings and help determining the timeframe of the window of opportunity for canakinumab treatment.
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