Horneff Gerd, Fitter Sigrid, Foeldvari Ivan, Minden Kirsten, Kuemmerle-Deschner Jasmin, Tzaribacev Nicolay, Thon Angelika, Borte Michael, Ganser Gerd, Trauzeddel Rolf, Huppertz Hans-Iko
Arthritis Res Ther. 2012 Oct 24;14(5):R230. doi: 10.1186/ar4072.
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).
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.
虽然阿达木单抗已获许可用于治疗强直性脊柱炎（AS），但开放性非对照研究表明肿瘤坏死因子抑制剂对青少年型强直性脊柱炎（JoAS）具有治疗效果。
共有32例年龄在12至17岁之间、患有严重、活动期且难治性JoAS的患者参加了一项为期12周的多中心、随机、双盲、安慰剂对照平行研究，之后所有患者接受开放标签的阿达木单抗治疗至第24周。采用ASAS40作为主要疗效指标，ASAS20、PedACR以及单项指标作为意向性治疗人群的次要疗效指标。
共有17例患者被随机分配接受每2周一次40mg阿达木单抗治疗，15例患者接受安慰剂治疗。两名患者（每组各一名）因疗效不佳而提前退出，被标记为无反应者。在双盲阶段，与安慰剂组相比，接受阿达木单抗治疗的患者在第4周（41%）、第8周（53%）和第12周（53%）达到ASAS40标准的人数更多，而安慰剂组分别为20%、33%和33%，其中仅第8周的差异接近显著水平（P = 0.05）。此外，在第4、8和12周时，阿达木单抗组的ASAS20/PedACR30/70反应率高于安慰剂组（分别为53%/53%/29%；59%/76%/41%；53%/65%/53%），安慰剂组则为27%/27%/7%；27%/33%/13%；33%/40%/27%。在阿达木单抗组中，所有疾病活动参数在第12周时均显著下降，在第24周时更为明显。在第12周时，巴斯强直性脊柱炎疾病活动脊柱炎症评分下降了65%（P <0.001），背痛评分下降了50%（P <0.005），巴斯强直性脊柱炎功能指数（BASFI）评分下降了47%（P <0.02），而儿童健康评估问卷残疾指数（CHAQ-DI）评分提高了65%（P <0.005）。协方差分析表明，在医生对疾病活动的整体评估、父母对受试者总体健康状况的整体评估、活动关节计数（所有P <0.05）以及红细胞沉降率（ESR）方面（P <0.01），阿达木单抗优于安慰剂。
在JoAS患者的双盲随机试验中，阿达木单抗耐受性良好且疗效显著。治疗效果迅速出现，并在至少24周的治疗期间持续存在。
EudraCT 2007-003358-27。
