Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial

Ruperto, Nicolino; Lovell, Daniel J.; Quartier, Pierre; Paz, Eliana; Rubio-Pérez, Nadina; Silva, Clóvis A.; Abud-Mendoza, Carlos; Burgos‐Vargas, Rubén; Gerloni, Valeria; Melo-Gomes, José; Saad‐Magalhães, Claudia; Sztajnbok, Flávio; Goldenstein-Schainberg, Cláudia; Scheinberg, Morton; Penades, I. Calvo; Fischbach, Michael; Orozco, Javier; Hashkes, Philip J.; Hom, Christine; Jung, Lawrence; Lepore, Loredana; Oliveira, Sheila Knupp Feitosa de; Wallace, Carol A.; Sigal, Leonard H.; Block, A. Jay; Covucci, Allison; Martini, Alberto; Giannini, Edward H.

doi:10.1016/s0140-6736(08)60998-8

Cited by 486 publications

(382 citation statements)

References 17 publications

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“…Abatacept was welltolerated during the 6 months of treatment. These results are consistent with those previously reported for abatacept therapy in RA (25), JIA (30), and psoriasis (31), suggesting that abatacept may provide clinicians another alternative therapy for PsA. In this study, the proportion of patients achieving an ACR20 response at an abatacept dosage of 10 mg/kg was higher in those who had not previously been treated with an anti-TNF agent than in those who had (56% versus 31%).…”

Section: Discussionsupporting

confidence: 92%

“…Abatacept selectively inhibits T cell activation via competitive binding to CD80 or CD86 and decreases serum levels of cytokines and inflammatory proteins implicated in the pathogenesis of PsA (24). Abatacept is an approved treatment for chronic inflammatory conditions such as rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), in which T cells are involved in the pathophysiology of the disease (25)(26)(27)(28)(29)(30). In a phase I study of abatacept in patients with psoriasis vulgaris, clinical improvement was associated with a reduction of the intralesional T cell population (31,32).…”

mentioning

confidence: 99%

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Abatacept in the treatment of patients with psoriatic arthritis: Results of a six‐month, multicenter, randomized, double‐blind, placebo‐controlled, phase II trial

Mease¹,

Genovese²,

Gladstein³

et al. 2011

Arthritis & Rheumatism

270

166

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Objective. To assess the safety and efficacy of abatacept, a selective T cell costimulation modulator, in patients with psoriatic arthritis (PsA).Methods. In this 6-month, multicenter, randomized, double-blind, placebo-controlled, phase II study, 170 PsA patients with a psoriasis target lesion (TL) >2 cm who had previously taken disease-modifying antirheumatic drugs (DMARDs), including anti-tumor necrosis factor (anti-TNF) agents, were randomized (1:1: 1:1) to receive placebo or abatacept at doses of 3 mg/kg, 10 mg/kg, or 30/10 mg/kg (2 initial doses of 30 mg/kg, followed by 10 mg/kg) on days 1, 15, and 29 and then once every 28 days thereafter. The primary end point was the American College of Rheumatology 20% criteria for improvement (ACR20 response) on day 169. Other key end points were magnetic resonance imaging (MRI) scores for joint erosion, osteitis, and synovitis, scores on the Health Assessment Questionnaire (HAQ) and the Short Form-36 (SF-36) health survey, the investigator's global assessment of psoriasis, the TL score, and the Psoriasis Area and Severity Index (PASI) score.Results. Proportions of patients achieving an ACR20 response were 19%, 33%, 48%, and 42% in the placebo, the abatacept 3 mg/kg, the abatacept 10 mg/kg, and the abatacept 30/10 mg/kg groups, respectively. Compared with placebo, improvements were significantly higher for the abatacept 10 mg/kg (P ‫؍‬ 0.006) and 30/10 mg/kg (P ‫؍‬ 0.022) groups, but not for 3 mg/kg group (P ‫؍‬ 0.121). All abatacept regimens resulted in improved MRI, HAQ, and SF-36 scores, with 10 mg/kg showing the greatest improvements. Improvements in the TL and PASI scores were observed in all abatacept arms; a response according to the investigator's global assessment was seen only with 3 mg/kg of abatacept. The safety profiles were similar among the treatment arms.Conclusion. The results of this study suggest that 10 mg/kg of abatacept, the approved dosage for rheumatoid arthritis and juvenile idiopathic arthritis, may be an effective treatment option for PsA.Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by both arthritis and psoriasis ClinicalTrials.gov identifier: NCT00534313.

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

Abatacept in the treatment of patients with psoriatic arthritis: Results of a six‐month, multicenter, randomized, double‐blind, placebo‐controlled, phase II trial

Mease¹,

Genovese²,

Gladstein³

et al. 2011

Arthritis & Rheumatism

270

166

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“…inflammatory features that tend to respond to anti-IL-1 therapies (6) and others following an arthritis-predominant disease course that may ultimately lead to chronic, destructive, treatment-refractory arthritis (7,8).…”

Section: Significancementioning

confidence: 99%

HLA-DRB111*and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis

Ombrello¹,

Remmers²,

Tachmazidou³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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146

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Systemic juvenile idiopathic arthritis (sJIA) is an often severe, potentially life-threatening childhood inflammatory disease, the pathophysiology of which is poorly understood. To determine whether genetic variation within the MHC locus on chromosome 6 influences sJIA susceptibility, we performed an association study of 982 children with sJIA and 8,010 healthy control subjects from nine countries. Using meta-analysis of directly observed and imputed SNP genotypes and imputed classic HLA types, we identified the MHC locus as a bona fide susceptibility locus with effects on sJIA risk that transcended geographically defined strata. The strongest sJIA-associated SNP, rs151043342 [P = 2.8 × 10−17, odds ratio (OR) 2.6 (2.1, 3.3)], was part of a cluster of 482 sJIA-associated SNPs that spanned a 400-kb region and included the class II HLA region. Conditional analysis controlling for the effect of rs151043342 found that rs12722051 independently influenced sJIA risk [P = 1.0 × 10−5, OR 0.7 (0.6, 0.8)]. Meta-analysis of imputed classic HLA-type associations in six study populations of Western European ancestry revealed that HLA-DRB1*11 and its defining amino acid residue, glutamate 58, were strongly associated with sJIA [P = 2.7 × 10−16, OR 2.3 (1.9, 2.8)], as was the HLA-DRB1*11—HLA-DQA1*05—HLA-DQB1*03 haplotype [6.4 × 10−17, OR 2.3 (1.9, 2.9)]. By examining the MHC locus in the largest collection of sJIA patients assembled to date, this study solidifies the relationship between the class II HLA region and sJIA, implicating adaptive immune molecules in the pathogenesis of sJIA.

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“…В анализах крови обнаружены значительные воспали-тельные сдвиги: повышение СОЭ до 42-52 мм/ч, увели-чение сывороточного уровня СРБ до 6,1-12,2 мг/л (N до 6) и ревматоидного фактора до 45-51 Ед/мл (N до 14), анемия хронического воспаления (число эритроцитов -3,6-3,9ϫ10 12 и КФК до 488-1078 Ед/л (N 24-170). По данным рентге-нологического исследования кистей определили измене-ние костной структуры костей запястий и проксимальных эпифизов пястных костей за счет остеопороза, признаки кистовидной перестройки III-IV пястных костей правой и II-III кости левой кисти.…”

Section: клинический примерunclassified

“…Абатацепт был одобрен FDA для лечения ЮИА с шести-летнего возраста в 2008 г. по результатам рандомизиро-ванного двойного слепого плацебоконтролируемого иссле-дования, проведенного под руководством N. Rupperto [12]. В исследовании показана высокая эффективность (82% ответов на 30% улучшение по критериям Американской коллегии ревматологов к 6-му мес двойной слепой фазы) и хорошую переносимость абатацепта.…”

Section: Introductionunclassified

Experience of Abatacept Treatment in a Patient With Seropositive Polyarthritis From Risk Group of Tuberculosis Infection

Балыкова¹,

Щёкина²,

Краснопольская³

et al. 2013

Vopr. sovr. pediatr.

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ВВЕДЕНИЕ Лечение ювенильного идиопатического артрита (ЮИА) -наиболее частого хронического воспалитель-ного заболевания суставов в детском возрасте -пред-ставляет собой одну из сложнейших задач ревматологии и педиатрии и на современном этапе развития науки включает, наряду с использованием стероидных, несте-роидных противовоспалительных и традиционных базис-ных средств (метотрексата и лефлуномида), назначение части детей генно-инженерных биологических препара-тов [1,2]. Последние, как правило, показаны пациен-там с тяжелыми полиартикулярными вариантами ЮИА и/или факторами неблагоприятного прогноза. Одной из относительно новых терапевтических стратегий «био-логического» лечения ЮИА наряду с блокадой отдельных провоспалительных цитокинов -фактора некроза опу-холи альфа (ФНО ␣), интерлейкинов (ИЛ) 1 и 6 является возможность подавления источника их продукции -активированных Т клеток [3].Препаратом с таким уникальным механизмом дей-ствия является абатацепт. Он представляет собой рас-творимый рекомбинантный полностью человеческий белок, состоящий из внеклеточного домена цитоток-сического Т-лимфоцитассоциированного антигена 4

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Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial

Cited by 486 publications

References 17 publications

Abatacept in the treatment of patients with psoriatic arthritis: Results of a six‐month, multicenter, randomized, double‐blind, placebo‐controlled, phase II trial

Abatacept in the treatment of patients with psoriatic arthritis: Results of a six‐month, multicenter, randomized, double‐blind, placebo‐controlled, phase II trial

HLA-DRB111*and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis

Experience of Abatacept Treatment in a Patient With Seropositive Polyarthritis From Risk Group of Tuberculosis Infection

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Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial

Cited by 486 publications

References 17 publications

Abatacept in the treatment of patients with psoriatic arthritis: Results of a six‐month, multicenter, randomized, double‐blind, placebo‐controlled, phase II trial

Abatacept in the treatment of patients with psoriatic arthritis: Results of a six‐month, multicenter, randomized, double‐blind, placebo‐controlled, phase II trial

HLA-DRB1*11and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis

Experience of Abatacept Treatment in a Patient With Seropositive Polyarthritis From Risk Group of Tuberculosis Infection

Contact Info

Product

Resources

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HLA-DRB111*and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis