Double-blind, placebo-controlled randomized trial with adalimumab for treatment of juvenile onset ankylosing spondylitis (JoAS): significant short term improvement.
Double-blind, placebo-controlled randomized trial with adalimumab for treatment of juvenile onset ankylosing spondylitis (JoAS): significant short term improvement.
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DOI：
10.1186/ar4072
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发表时间：
2012-10-24
影响因子：
4.9
通讯作者：
Huppertz HI
中科院分区：
文献类型：
--
作者：
Horneff G;Fitter S;Foeldvari I;Minden K;Kuemmerle-Deschner J;Tzaribacev N;Thon A;Borte M;Ganser G;Trauzeddel R;Huppertz HI
虽然阿达木单抗被许可用于治疗强直性脊柱炎（AS），但开放的非对照研究表明TNF抑制剂在青少年发作AS（JoAS）中具有疗效。一项为期12周的多中心、随机化、双盲、安慰剂对照平行研究共入组了32例12 - 17岁的重度、活动性和难治性JoAS患者，随后所有患者接受开放标签阿达木单抗治疗直至第24周。ASAS 40被用作意向治疗人群的主要结局指标，ASAS 20、PedACR和单项被用作意向治疗人群的次要结局指标。共有17例患者随机接受阿达木单抗40 mg/2周，15例患者接受安慰剂。两名患者（每组各一名）因疗效不足而提前停药，并被标记为无应答者。在双盲部分，阿达木单抗组第4周（41%）、第8周（53%）和第12周（53%）达到ASAS 40的患者多于安慰剂组（20%、33%、33%），而第8周的差异仅达到临界显著性（P = 0.05）。此外，在第4、8和12周，阿达木单抗组的ASAS 20/PedACR 30/70应答率（53%/53%/29%; 59%/76%/41%; 53%/65%/53%）高于安慰剂组（27%/27%/7%; 27%/33%/13%; 33%/40%/27%）。在阿达木单抗组中，在第12周时观察到所有疾病活动性参数显著降低，在第24周时甚至更明显。在第12周，Bath强直性脊柱炎疾病活动性脊柱炎症评分降低了65%（P <0.001），背痛评分下降50% Bath AS功能指数（BASFI）评分下降47%（P <0.005）儿童健康评估量表（CHAQ-DI）评分提高65%（P <0.005）。ANCOVA分析表明，阿达木单抗在医生对疾病活动性的总体评估、父母对受试者总体健康状况的总体评估、活动关节计数（均P <0.05）和红细胞沉降率（ESR）（P <0.01）方面优于安慰剂。在12周对照期内，安慰剂组10例患者发生29起AE，阿达木单抗组11例患者发生27起AE。注射部位反应是最常见的不良事件。双盲期发生17例各种感染，安慰剂组8例，阿达木单抗组9例，开放标签期另外19例。在JoAS患者中进行的一项双盲随机试验中，阿达木单抗耐受性良好且高效。治疗效果迅速出现，并持续至少24周的治疗。EudraCT 2007-003358-27。
While adalimumab is licensed for ankylosing spondylitis (AS), open uncontrolled studies suggest therapeutic efficacy of TNF-inhibitors in juvenile onset AS (JoAS). A total of 32 patients aged 12 to 17 years with severe, active and refractory JoAS were enrolled in a multicenter, randomized, double-blind, placebo-controlled parallel study of 12 weeks, followed by open-label adalimumab until week 24 for all patients. ASAS40 was used as the primary, and ASAS20, PedACR and single items were used as the secondary outcome measures for the intention to treat population. A total of 17 patients were randomized to receive adalimumab 40 mg/2 weeks and 15 patients received placebo. Two patients (one of each group) discontinued prematurely due to insufficient efficacy and were labeled as non-responders. In the double-blind part, more patients on adalimumab achieved an ASAS40 at week 4 (41%), week 8 (53%) and week 12 (53%) than on placebo (20%, 33%, 33%), while differences at week 8 only reached borderline significance (P = 0.05). Also, at 4, 8 and 12 weeks ASAS20/PedACR30/70 response rates were higher in the adalimumab group (53%/53%/29%; 59%/76%/41%; 53%/65%/53%) compared to placebo (27%/27%/7%; 27%/33%/13%; 33%/40%/27%). In the adalimumab group a significant decrease of all disease activity parameters was noted at week 12 and was even more pronounced at week 24. At week 12 the Bath Ankylosing Spondylitis Disease activity spinal inflammation score decreased by 65% (P <0.001), the back pain score decreased by 50% (P <0.005), the Bath AS Functional Index (BASFI) score decreased by 47% (P <0.02), while the Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) score improved by 65% (P <0.005). ANCOVA analysis demonstrated superiority of adalimumab over placebo for the physician global assessment of disease activity, parents' global assessment of subject's overall well-being, active joint count (all P <0.05) and erythrocyte sedimentation rate (ESR) (P <0.01). During the 12-week controlled phase, 29 AEs occurred in 10 patients on placebo compared to 27 AEs in 11 patients on adalimumab. Injection site reactions were the most common adverse events. There were 17 various infections occurring in the double-blind phase, 8 on placebo, 9 on adalimumab and a further 19 in the open label period. Adalimumab was well tolerated and highly effective in a double-blind randomized trial in patients with JoAS. Treatment effects rapidly occurred and persisted for at least 24 weeks of treatment. EudraCT 2007-003358-27.
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