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Juvenile idiopathic arthritis- systemic

Disease ID:1176
Name:Juvenile idiopathic arthritis- systemic
Associated with:0 target
4 immuno-relevant ligands
systemic juvenile rheumatoid arthritis
A subtype of juvenile idiopathic arthritis which affects the whole body, causing fever and rashes. Biologic drugs approved to treat systemic JIA include tocilizumab and canakinumab. This is a complex condition, with susceptibility influenced by many factors, including genetic polymorphisms.
Database Links
OMIM: 604302


No target related data available for Juvenile idiopathic arthritis- systemic


Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
Immuno Disease Comments: Approved drug for JIA.
Clinical Use: Used to treat moderate to severe rheumatoid arthritis and juvenile rheumatoid arthritis. In July 2017, FDA approval was extended to include treatment of active psoriatic arthritis.
A Phase 2 clinical trial (NCT00505375) has been completed, evaluating the ability of abatacept to stop autoimmune destruction of any remaining active β cells in patients recently diagnosed with type 1 diabetes mellitus- see [7] for an explanation of the rationale behind this therapeutic approach, and [3] which points to some of its drawbacks. | View clinical data
Bioactivity Comments: In a cell based CD80/86 inhibition assay abatacept inhibits IL-2 release with an IC50 of 22.6 nM [4]. | View biological activity
Immuno Disease Comments: An anti-IL-6 therapy approved for sJIA.
Clinical Use: Tocilizumab had been approved in Japan in 2005 as a treament for giant lymph node hyperplasia (Castleman's disease) [10], before being granted EMA and FDA approvals for use as a treatment for rheumatoid arthritis [9,11] and systemic and polyarticular juvenile idiopathic arthritis [14].
In May 2017 tocilizumab became the first FDA approved drug for the treatment of adults with giant cell arteritis.
Phase 3 clinical trials for immune conditions including ankylosing spondylitis, hand osteoarthritis, systemic sclerosis and primary Sjögren's syndrome (pSS) are ongoing. Tocilizumab was initally used off-label to manage severe or life-threatening cytokine release syndrome (CRS), which is a serious, and potentially life-threatening side effect of CAR T-cell therapy. In September 2017, the FDA extended tocilizumab approval to include treatment of CAR T-cell therapy-induced CRS. It was approved particularly to manage CRS in patients ≥2 years of age receiving tisagenlecleucel (Kymriah®,CTL019), the first CAR T-cell therapy approved for relapsed and refractory B-cell ALL.

SARS-CoV-2 and COVID-19: China's National Health Commission authorised tocilizumab as a treatment for serious COVID-19 lung damage early on in the outbreak. The Chinese Clinical Trial Registry has two studies that are designed to evaluate tocilizumab efficacy in patients with severe COVID-19 pneumonia (Registration Numbers ChiCTR2000029765 and ChiCTR2000030442). Results from an observational study, of low-dose tocilizumab in patients with confirmed elevations in inflammatory markers, showed an indication of reduced mortality [1]. This finding was not confirmed by preliminary results from Roche's Phase 3 COVACTA RCT (NCT04320615). The limitations and differences between the studies, and reasoning that might explain the apparently contradictory findings are discussed by Campochiaro and Dagna (2020) [2]. In addition, early results from 20 severe COVID-19 patients treated with tocilizumab have been posted on the preprint server of the Chinese Academy of Sciences (ChinaRix) (url, DOI: 10.12074/202003.00026). Tocilizumab appears to have reduced disease symptoms and aided full recovery in 19/20 patients. In mid-March 2020, the National Cancer Institute in Naples (Italy) began a Phase 2 observational trial of tocilizumab in patients with COVID-19 pneumonia; this study is named TOCIVID-19, and has registry ID NCT04317092. | View clinical data
Bioactivity Comments: Unfortunately, we have been unable to find publicly available data providing a binding affinity for this antibody at its molecular target. | View biological activity
canakinumab 12
Immuno Disease Comments: An anti-IL-1β therapeutic approved for sJIA.
Clinical Use: Used to treat rheumatic diseases; familial cold autoinflammatory syndrome (FCAS) [6] and Muckle-Wells syndrome (MWS) in patients >4 years of age, systemic juvenile idiopathic arthritis (sJIA) in patients >2 years old [12], and adult-onset Still's disease.

Unexpectedly, further analysis of data from the CANTOS cardiovascular disease trial revealed that IL-1β inhibition significantly reduced the incidence of hip and knee replacements compared to those not treated with canakinumab, suggesting application of canakinumab as a large joint osteoarthritis therapeutic [13].

SARS-CoV-2 and COVID-19: Canakinumab has been entered in to clinical trials that aim to determine its ability to combat the exaggerated immune response that drives cytokine storm and leads to tissue damage in the lung and other organs in patients with severe COVID-19. | View clinical data
Immuno Disease Comments: Approved corticosteroid that can be prescribed for sJIA.
Clinical Use: Deflazacort can be prescribed for many inflammatory conditions including asthma, rheumatoid arthritis, Crohn's disease, juvenile chronic arthritis, idiopathic thrombocytopenic purpura, polymyalgia rheumatica, systemic lupus erythematosus and ulcerative colitis. More recently approved by the FDA as a treatment for Duchenne muscular dystrophy [5]. | View clinical data
Bioactivity Comments: In vitro binding to rat kidney, thymus and liver glucocorticoid receptors is reported in [8]. | View biological activity


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1. Biran N, Ip A, Ahn J, Go RC, Wang S, Mathura S, Sinclaire BA, Bednarz U, Marafelias M, Hansen E et al.. (2020) Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study. The Lancet, [Epub ahead of print]. DOI: 10.1016/S2665-9913(20)30277-0

2. Campochiaro C, Dagna L. (2020) The conundrum of interleukin-6 blockade in COVID-19. The Lancet, [Epub ahead of print]. DOI: 10.1016/S2665-9913(20)30287-3

3. Davis IC, Randell J, Davis SN. (2015) Immunotherapies currently in development for the treatment of type 1 diabetes. Expert Opin Investig Drugs, 24 (10): 1331-41. [PMID:26364507]

4. Douthwaite J, Moisan J, Privezentzev C, Soskic B, Sabbah S, Cohen S, Collinson A, England E, Huntington C, Kemp B et al.. (2017) A CD80-Biased CTLA4-Ig Fusion Protein with Superior In Vivo Efficacy by Simultaneous Engineering of Affinity, Selectivity, Stability, and FcRn Binding. J Immunol, 198 (1): 528-537. [PMID:27881707]

5. Griggs RC, Miller JP, Greenberg CR, Fehlings DL, Pestronk A, Mendell JR, Moxley 3rd RT, King W, Kissel JT, Cwik V et al.. (2016) Efficacy and safety of deflazacort vs prednisone and placebo for Duchenne muscular dystrophy. Neurology, 87 (20): 2123-2131. [PMID:27566742]

6. Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, Quartier P, Gitton X, Widmer A, Patel N, Hawkins PN et al.. (2009) Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med, 360 (23): 2416-25. [PMID:19494217]

7. Ludvigsson J. (2016) Therapies to Preserve β-Cell Function in Type 1 Diabetes. Drugs, 76 (2): 169-85. [PMID:26645223]

8. Luzzani F, Glässer A. (1981) Differential binding in vitro to glucocorticoid receptors of deflazacort and prednisolone. Eur J Pharmacol, 76 (4): 427-30. [PMID:7327211]

9. Maini RN, Taylor PC, Szechinski J, Pavelka K, Bröll J, Balint G, Emery P, Raemen F, Petersen J, Smolen J et al.. (2006) Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum, 54 (9): 2817-29. [PMID:16947782]

10. Matsuyama M, Suzuki T, Tsuboi H, Ito S, Mamura M, Goto D, Matsumoto I, Tsutsumi A, Sumida T. (2007) Anti-interleukin-6 receptor antibody (tocilizumab) treatment of multicentric Castleman's disease. Intern Med, 46 (11): 771-4. [PMID:17541233]

11. Ohsugi Y, Kishimoto T. (2008) The recombinant humanized anti-IL-6 receptor antibody tocilizumab, an innovative drug for the treatment of rheumatoid arthritis. Expert Opin Biol Ther, 8 (5): 669-81. [PMID:18407769]

12. Ruperto N, Brunner HI, Quartier P, Constantin T, Wulffraat N, Horneff G, Brik R, McCann L, Kasapcopur O, Rutkowska-Sak L et al.. (2012) Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med, 367 (25): 2396-406. [PMID:23252526]

13. Schieker M, Conaghan PG, Mindeholm L, Praestgaard J, Solomon DH, Scotti C, Gram H, Thuren T, Roubenoff R, Ridker PM. (2020) Effects of Interleukin-1β Inhibition on Incident Hip and Knee Replacement : Exploratory Analyses From a Randomized, Double-Blind, Placebo-Controlled Trial. Ann Intern Med, 173 (7): 509-515. [PMID:32744862]

14. Yokota S, Miyamae T, Imagawa T, Katakura S, Kurosawa R, Mori M. (2005) Clinical study of tocilizumab in children with systemic-onset juvenile idiopathic arthritis. Clin Rev Allergy Immunol, 28 (3): 231-8. [PMID:16129907]