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Abatacept in difficult-to-treat juvenile idiopathic arthritis.

Kuemmerle-Deschner JB, Benseler S - Biologics (2008)

Bottom Line: Abatacept (ABA), a selective co-stimulation modulator, has been shown to be effective in treating all JIA subtypes and is generally safe and well tolerated in JIA.Neutralizing antibodies were found in 6/9 (67%) of seropositive patients, but anti-ABA antibodies did not appear to be associated with disease flare, serious adverse events, acute infusional adverse events, hypersensitivity, autoimmune disorders, or low ABA serum concentrations.Although information on ABA in JIA is still limited, available data suggest a potential role in difficult to treat JIA patients previously treated with other biologic agents and for non-responders to TNF-blockade.

View Article: PubMed Central - PubMed

Affiliation: Pediatric Rheumatology Clinics, Dept of Pediatrics, University Hospital Tübingen, Germany;

ABSTRACT
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and an important cause of short-term and long-term disability. Gene changes in the immune system can predispose to JIA and regulation of the immune system is crucial in the pathogenesis. The goal of therapy is complete disease control using disease-modifying antirheumatic drugs (DMARDS). Activated T-cells may play a role in the immunopathology of JIA. Therefore, targeting T-cell activation is a rational approach for the treatment of JIA. Abatacept (ABA), a selective co-stimulation modulator, has been shown to be effective in treating all JIA subtypes and is generally safe and well tolerated in JIA. Neutralizing antibodies were found in 6/9 (67%) of seropositive patients, but anti-ABA antibodies did not appear to be associated with disease flare, serious adverse events, acute infusional adverse events, hypersensitivity, autoimmune disorders, or low ABA serum concentrations. Anti-ABA antibodies were more frequent when ABA concentrations were below therapeutic levels. Although information on ABA in JIA is still limited, available data suggest a potential role in difficult to treat JIA patients previously treated with other biologic agents and for non-responders to TNF-blockade.

No MeSH data available.


Related in: MedlinePlus

Flare-free survival of patients with juvenile idiopathic arthritis (JIA) treated with either abatacept or placebo. The graph demonstrates the proportion of patients without disease flare during the 6-month double-blind period. P value represents the comparison of the time to disease flare between the abatacept and placebo groups. Adapted from The Lancet, 372, Ruperto N, Lovell DJ, Quartier P, et al; Paediatric Rheumatology International Trials Organization; Pediatric Rheumatology Collaborative Study Group. 2008. Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial, 383–91, Copyright © 2008 with permission from Elsevier.
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f3-btt-2-865: Flare-free survival of patients with juvenile idiopathic arthritis (JIA) treated with either abatacept or placebo. The graph demonstrates the proportion of patients without disease flare during the 6-month double-blind period. P value represents the comparison of the time to disease flare between the abatacept and placebo groups. Adapted from The Lancet, 372, Ruperto N, Lovell DJ, Quartier P, et al; Paediatric Rheumatology International Trials Organization; Pediatric Rheumatology Collaborative Study Group. 2008. Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial, 383–91, Copyright © 2008 with permission from Elsevier.

Mentions: A significantly higher flare rate was observed in placebo-treated patients than ABA-treated patients over 6 months. A total of 33/62 (53%) placebo-treated patients flared and were switched to open-label ABA. In contrast, only 12/60 (20%) ABA-treated patients flared (p = 0.002, Figure 3). In the ABA group, 49/60 completed the 6-month randomized phase, whereas only 31/62 placebo treated children did. Unfortunately, no information is provided about the JIA subtypes that either had sustained responses or disease flares.


Abatacept in difficult-to-treat juvenile idiopathic arthritis.

Kuemmerle-Deschner JB, Benseler S - Biologics (2008)

Flare-free survival of patients with juvenile idiopathic arthritis (JIA) treated with either abatacept or placebo. The graph demonstrates the proportion of patients without disease flare during the 6-month double-blind period. P value represents the comparison of the time to disease flare between the abatacept and placebo groups. Adapted from The Lancet, 372, Ruperto N, Lovell DJ, Quartier P, et al; Paediatric Rheumatology International Trials Organization; Pediatric Rheumatology Collaborative Study Group. 2008. Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial, 383–91, Copyright © 2008 with permission from Elsevier.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2727897&req=5

f3-btt-2-865: Flare-free survival of patients with juvenile idiopathic arthritis (JIA) treated with either abatacept or placebo. The graph demonstrates the proportion of patients without disease flare during the 6-month double-blind period. P value represents the comparison of the time to disease flare between the abatacept and placebo groups. Adapted from The Lancet, 372, Ruperto N, Lovell DJ, Quartier P, et al; Paediatric Rheumatology International Trials Organization; Pediatric Rheumatology Collaborative Study Group. 2008. Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial, 383–91, Copyright © 2008 with permission from Elsevier.
Mentions: A significantly higher flare rate was observed in placebo-treated patients than ABA-treated patients over 6 months. A total of 33/62 (53%) placebo-treated patients flared and were switched to open-label ABA. In contrast, only 12/60 (20%) ABA-treated patients flared (p = 0.002, Figure 3). In the ABA group, 49/60 completed the 6-month randomized phase, whereas only 31/62 placebo treated children did. Unfortunately, no information is provided about the JIA subtypes that either had sustained responses or disease flares.

Bottom Line: Abatacept (ABA), a selective co-stimulation modulator, has been shown to be effective in treating all JIA subtypes and is generally safe and well tolerated in JIA.Neutralizing antibodies were found in 6/9 (67%) of seropositive patients, but anti-ABA antibodies did not appear to be associated with disease flare, serious adverse events, acute infusional adverse events, hypersensitivity, autoimmune disorders, or low ABA serum concentrations.Although information on ABA in JIA is still limited, available data suggest a potential role in difficult to treat JIA patients previously treated with other biologic agents and for non-responders to TNF-blockade.

View Article: PubMed Central - PubMed

Affiliation: Pediatric Rheumatology Clinics, Dept of Pediatrics, University Hospital Tübingen, Germany;

ABSTRACT
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and an important cause of short-term and long-term disability. Gene changes in the immune system can predispose to JIA and regulation of the immune system is crucial in the pathogenesis. The goal of therapy is complete disease control using disease-modifying antirheumatic drugs (DMARDS). Activated T-cells may play a role in the immunopathology of JIA. Therefore, targeting T-cell activation is a rational approach for the treatment of JIA. Abatacept (ABA), a selective co-stimulation modulator, has been shown to be effective in treating all JIA subtypes and is generally safe and well tolerated in JIA. Neutralizing antibodies were found in 6/9 (67%) of seropositive patients, but anti-ABA antibodies did not appear to be associated with disease flare, serious adverse events, acute infusional adverse events, hypersensitivity, autoimmune disorders, or low ABA serum concentrations. Anti-ABA antibodies were more frequent when ABA concentrations were below therapeutic levels. Although information on ABA in JIA is still limited, available data suggest a potential role in difficult to treat JIA patients previously treated with other biologic agents and for non-responders to TNF-blockade.

No MeSH data available.


Related in: MedlinePlus