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Abatacept in the treatment of polyarticular JIA: development, clinical utility, and place in therapy.

Goldzweig O, Hashkes PJ - Drug Des Devel Ther (2011)

Bottom Line: In a randomized, multinational, blinded withdrawal study in children with polyarticular JIA, abatacept was found to be effective in about 70% of the patients, including 39% of TNF-α blockade failures, with significantly fewer flares occurring during the withdrawal phase than in patients receiving placebo.Abatacept continued to show good efficacy in a three-year open-label extension study, with a beneficial effect on health-related quality of life.The safety profile of abatacept is generally good.

View Article: PubMed Central - PubMed

Affiliation: Rainbow Babies and Children's Hospital, Cleveland, OH, USA.

ABSTRACT
Juvenile idiopathic arthritis (JIA) is a group of chronic arthritides affecting children. The polyarthritis category, affecting five or more joints in the first six months, tends to be more aggressive, leading to a destructive joint disease with significant morbidity, disability, and costs to society. The current treatment regimen, which primarily combines methotrexate and tumor necrosis factor alpha (TNF-α) blockade, still leaves a significant group of patients with an inadequate response. Therefore, the development of new medications that act via other mechanisms of pathogenesis is necessary. T cell lymphocytes are key components in the immune reaction in JIA. Cytotoxic lymphocyte-associated antigen-4 (CTLA-4) is a potent inhibitor of the costimulation pathway necessary to activate T cells. Abatacept is a recombinant fusion protein comprising the extracellular part of human CTLA-4 connected to a modified Fc part of IgG-1. In a randomized, multinational, blinded withdrawal study in children with polyarticular JIA, abatacept was found to be effective in about 70% of the patients, including 39% of TNF-α blockade failures, with significantly fewer flares occurring during the withdrawal phase than in patients receiving placebo. Abatacept continued to show good efficacy in a three-year open-label extension study, with a beneficial effect on health-related quality of life. The safety profile of abatacept is generally good. In 2008, the US Food and Drug Administration approved abatacept for use in children over six years of age with JIA and a polyarticular course. In 2010, the European Medicines Agency gave approval for abatacept to be used in combination with methotrexate for those who fail at least one disease-modifying medication and TNF-α blockade.

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A flow chart of patient disposition in various phases of the abatacept trial.27Note: One responder was not randomized.Abbreviations: ACR, American College of Rheumatology; Pedi, pediatric; LTe, long-term extension.
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f2-dddt-5-061: A flow chart of patient disposition in various phases of the abatacept trial.27Note: One responder was not randomized.Abbreviations: ACR, American College of Rheumatology; Pedi, pediatric; LTe, long-term extension.

Mentions: One hundred and ninety patients entered the open-label, lead-in phase of the study; 147 (77%) were Caucasian, and 137 (72%) were females (Figure 2). Rheumatoid factor-negative polyarthritis was the most common diagnosis (44%). The mean disease duration was 4.2 years. Patients had a mean of 16 active joints. More than 70% were treated with concurrent methotrexate, and more than 30% had been treated unsuccessfully with at least one TNF-α blocking agent. In the first phase, all patients received abatacept 10 mg/kg (maximum 1000 mg per dose) on days 1, 15, 29, 57, and 85. Seventeen patients discontinued because the treatment was ineffective, one withdrew because of an adverse effect, one was lost to follow-up, and no reason was stated for one patient. By the end of the lead-in phase, 123 subjects (65%) were considered responders at least at an ACR Pediatric 30 response level. Twenty-four (13%) patients attained a status of inactive disease (definition in Table 3). There were no significant differences in response rates between the various categories of JIA with a polyarticular course.


Abatacept in the treatment of polyarticular JIA: development, clinical utility, and place in therapy.

Goldzweig O, Hashkes PJ - Drug Des Devel Ther (2011)

A flow chart of patient disposition in various phases of the abatacept trial.27Note: One responder was not randomized.Abbreviations: ACR, American College of Rheumatology; Pedi, pediatric; LTe, long-term extension.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3038996&req=5

f2-dddt-5-061: A flow chart of patient disposition in various phases of the abatacept trial.27Note: One responder was not randomized.Abbreviations: ACR, American College of Rheumatology; Pedi, pediatric; LTe, long-term extension.
Mentions: One hundred and ninety patients entered the open-label, lead-in phase of the study; 147 (77%) were Caucasian, and 137 (72%) were females (Figure 2). Rheumatoid factor-negative polyarthritis was the most common diagnosis (44%). The mean disease duration was 4.2 years. Patients had a mean of 16 active joints. More than 70% were treated with concurrent methotrexate, and more than 30% had been treated unsuccessfully with at least one TNF-α blocking agent. In the first phase, all patients received abatacept 10 mg/kg (maximum 1000 mg per dose) on days 1, 15, 29, 57, and 85. Seventeen patients discontinued because the treatment was ineffective, one withdrew because of an adverse effect, one was lost to follow-up, and no reason was stated for one patient. By the end of the lead-in phase, 123 subjects (65%) were considered responders at least at an ACR Pediatric 30 response level. Twenty-four (13%) patients attained a status of inactive disease (definition in Table 3). There were no significant differences in response rates between the various categories of JIA with a polyarticular course.

Bottom Line: In a randomized, multinational, blinded withdrawal study in children with polyarticular JIA, abatacept was found to be effective in about 70% of the patients, including 39% of TNF-α blockade failures, with significantly fewer flares occurring during the withdrawal phase than in patients receiving placebo.Abatacept continued to show good efficacy in a three-year open-label extension study, with a beneficial effect on health-related quality of life.The safety profile of abatacept is generally good.

View Article: PubMed Central - PubMed

Affiliation: Rainbow Babies and Children's Hospital, Cleveland, OH, USA.

ABSTRACT
Juvenile idiopathic arthritis (JIA) is a group of chronic arthritides affecting children. The polyarthritis category, affecting five or more joints in the first six months, tends to be more aggressive, leading to a destructive joint disease with significant morbidity, disability, and costs to society. The current treatment regimen, which primarily combines methotrexate and tumor necrosis factor alpha (TNF-α) blockade, still leaves a significant group of patients with an inadequate response. Therefore, the development of new medications that act via other mechanisms of pathogenesis is necessary. T cell lymphocytes are key components in the immune reaction in JIA. Cytotoxic lymphocyte-associated antigen-4 (CTLA-4) is a potent inhibitor of the costimulation pathway necessary to activate T cells. Abatacept is a recombinant fusion protein comprising the extracellular part of human CTLA-4 connected to a modified Fc part of IgG-1. In a randomized, multinational, blinded withdrawal study in children with polyarticular JIA, abatacept was found to be effective in about 70% of the patients, including 39% of TNF-α blockade failures, with significantly fewer flares occurring during the withdrawal phase than in patients receiving placebo. Abatacept continued to show good efficacy in a three-year open-label extension study, with a beneficial effect on health-related quality of life. The safety profile of abatacept is generally good. In 2008, the US Food and Drug Administration approved abatacept for use in children over six years of age with JIA and a polyarticular course. In 2010, the European Medicines Agency gave approval for abatacept to be used in combination with methotrexate for those who fail at least one disease-modifying medication and TNF-α blockade.

Show MeSH
Related in: MedlinePlus