Asklepios Clinic Sankt Augustin, Sankt Augustin, Germany.
Hamburg Center for Pediatric Rheumatology, Hamburg, Germany.
Arthritis Rheumatol. 2015 May;67(8):2240-9. doi: 10.1002/art.39145.
To evaluate the efficacy and safety of etanercept in patients with enthesitis-related arthritis (ERA) in juvenile idiopathic arthritis (JIA).
This was a 2-phase study in JIA patients with active, refractory ERA. Phase I was an open-label, uncontrolled 24-week study period in which all patients were administered etanercept. Patients considered to be treatment responders at week 24 according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) criteria for improvement in juvenile arthritis entered the second phase, a 24-week randomized, double-blind, placebo-controlled withdrawal study, for an additional 24 weeks, for evaluation of the primary end point, occurrence of a disease flare from week 24 to week 48, based on the ACR preliminary definition of disease flare in juvenile arthritis.
Forty-one patients were enrolled. At week 24, treatment with etanercept resulted in response rates of 93%, 93%, 80%, 56%, and 54% based on the ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria, respectively. In addition, a marked decrease in all disease activity measures was observed. The mean number of tender joints, swollen joints, and joints with active arthritis decreased by 91%, 97%, and 94%, respectively. Physician's global assessment of disease activity, parent's assessment of patient's overall well-being, and the Childhood Health Assessment Questionnaire disability index improved by 91%, 80%, and 86%, respectively. The number of tender enthesis sites and total scores for back pain, nocturnal pain, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, and Juvenile Arthritis Disease Activity Score based on 10-joint counts (JADAS10) decreased by 75%, 72%, 81%, 72%, 85%, and 87%, respectively. In phase II, 38 patients were randomly assigned to receive placebo (n = 18) or to continue receiving etanercept (n = 20). Up to week 48, 12 disease flares occurred, in 9 patients receiving placebo and 3 patients receiving etanercept (odds ratio 6.0, P = 0.02). There were no serious infections, malignancies, or deaths.
In this study of patients with the ERA category of JIA, etanercept proved effective, as indicated by high ACR Pedi response rates and JADAS10 response rates at week 24. Patients who continued treatment with etanercept had significantly fewer flares than those who received placebo, although 50% of patients in the placebo group did not experience a flare. Treatment suspension may be a consideration for patients with the ERA category of JIA who achieve remission.
评估依那西普在幼年特发性关节炎（JIA）中附着点相关关节炎（ERA）患者中的疗效和安全性。
这是一项在 JIA 伴有活动性、难治性 ERA 的患者中进行的 2 期研究。第 1 阶段是开放标签、无对照的 24 周研究期，所有患者均接受依那西普治疗。根据美国风湿病学会（ACR）儿童 30 项（Pedi 30）改善幼年关节炎的标准，在第 24 周被认为是治疗应答者的患者进入第 2 阶段，即另外 24 周的随机、双盲、安慰剂对照撤药研究，以评估主要终点，即从第 24 周到第 48 周发生疾病复发的情况，该终点基于 ACR 对幼年关节炎疾病复发的初步定义。
共纳入 41 例患者。在第 24 周时，依那西普治疗的应答率分别为 ACR Pedi 30、Pedi 50、Pedi 70、Pedi 90 和 Pedi 100 标准的 93%、93%、80%、56%和 54%。此外，所有疾病活动度指标均显著下降。压痛关节数、肿胀关节数和活动关节炎关节数分别减少了 91%、97%和 94%。医生总体疾病活动度评估、父母对患者整体健康状况的评估以及儿童健康评估问卷残疾指数分别改善了 91%、80%和 86%。压痛附着点部位数和腰痛、夜间痛、Bath 强直性脊柱炎疾病活动指数、Bath 强直性脊柱炎功能指数以及基于 10 个关节计数的幼年关节炎疾病活动评分（JADAS10）的总评分分别减少了 75%、72%、81%、72%、85%和 87%。在第 2 阶段，38 例患者被随机分配接受安慰剂（n=18）或继续接受依那西普（n=20）治疗。直至第 48 周，安慰剂组有 9 例（12 次疾病复发）和依那西普组有 3 例（3 次疾病复发）患者发生疾病复发（比值比 6.0，P=0.02）。无严重感染、恶性肿瘤或死亡发生。
在这项 JIA 的 ERA 类别的患者研究中，依那西普的疗效显著，第 24 周时 ACR Pedi 应答率和 JADAS10 应答率较高。继续接受依那西普治疗的患者比接受安慰剂治疗的患者发生疾病复发的情况显著减少，尽管安慰剂组的 50%患者未发生疾病复发。对于达到缓解的 ERA 类别的 JIA 患者，暂停治疗可能是一种考虑。
