Nejvíce citovaný článek - PubMed ID 19328245
Prospective new biological therapies for rheumatoid arthritis
Advances in the treatment of rheumatoid arthritis (RA) are attributed to several aspects such as new classification criteria enabling early diagnosis and intensive treatment with the application of treat-to-target principles as well as better understanding of the pathogenesis of RA contributing to the development of targeted therapies. However, reaching remission is still not achieved in most patients with RA, which is one of the driving forces behind the continuous development of novel therapies and the optimization of therapeutic strategies. This review will outline several new therapeutic antibodies modulating anti-inflammatory cytokines interleukin (IL)-2 and IL-10 and pro-inflammatory mediators granulocyte-macrophage colony-stimulating factor, fractalkine, and IL-6 that are in various stages of clinical development as well as the progress in manufacturing biotechnologies contributing to the next generation of antibodies and their potential to expand the therapeutic armamentarium for RA. In addition, the fate of unsuccessful therapies including agents targeting IL-15, the IL-20 family, IL-21, chemokine CXCL10, B-cell activating factor (BAFF), and regulatory T (Treg) cells or a novel concept targeting synovial fibroblasts via cadherin-11 will be discussed.
- Klíčová slova
- biological therapies, monoclonal antibodies, rheumatoid arthritis, therapeutic strategies,
- MeSH
- cytokiny imunologie MeSH
- fibroblasty účinky léků MeSH
- lidé MeSH
- monoklonální protilátky terapeutické užití MeSH
- revmatoidní artritida terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- cytokiny MeSH
- monoklonální protilátky MeSH
OBJECTIVES: To study the association of systemic and local interleukin-35 (IL-35) levels in rheumatoid arthritis. METHODS: 37 patients with treatment naïve early RA, 49 with established RA and 29 control patients with osteoarthritis (OA) were studied. Serum and paired synovial fluid samples were analysed for IL-35. Disease activity of RA patients was assessed according to the 28-Joint Count Disease Activity Score (DAS28). RESULTS: The levels of serum IL-35 were significantly higher in patients with treatment naïve early RA compared to those with established disease and control OA subjects. In addition, serum levels of IL-35 significantly decreased 12 weeks after initiation of glucocorticoids and conventional synthetic disease modifying antirheumatic drugs in patients with treatment naïve early RA. Synovial fluid IL-35 levels were significantly higher in RA compared to OA patients, were significantly elevated compared to serum counterparts and correlated with synovial fluid leukocyte count (r=0.412; p<0.01), serum CRP levels (r=0.362; p<0.05) and DAS28 (r=0.430, p<0.01). CONCLUSION: This is the first study showing elevated circulating levels of IL-35 in treatment naïve early RA, its significant decrease after treatment initiation and positive association between increased synovial fluid IL-35 and disease activity in patients with long-lasting RA.
- MeSH
- antirevmatika terapeutické užití MeSH
- biologické markery MeSH
- dospělí MeSH
- glukokortikoidy terapeutické užití MeSH
- imunosupresiva terapeutické užití MeSH
- interleukiny analýza krev fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- revmatoidní artritida farmakoterapie metabolismus MeSH
- stupeň závažnosti nemoci MeSH
- synoviální tekutina chemie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- antirevmatika MeSH
- biologické markery MeSH
- glukokortikoidy MeSH
- imunosupresiva MeSH
- interleukin-35, human MeSH Prohlížeč
- interleukiny MeSH