Probity Medical Research, Waterloo, ON, Canada.
Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany.
Lancet. 2017 Jul 1;390(10089):40-49. doi: 10.1016/S0140-6736(17)31189-3. Epub 2017 May 4.
Adalimumab is indicated for the treatment of moderate to severe psoriasis in adults. We assessed the efficacy and safety of adalimumab in children and adolescents with severe plaque psoriasis.
This randomised, double-blind, multiperiod, phase 3 trial was done at 38 clinics in 13 countries. Patients (aged ≥4 to <18 years) with severe plaque psoriasis who had not responded to topical therapy were randomly assigned with an interactive voice or web-response system (1:1:1) to receive adalimumab 0·8 mg/kg or 0·4 mg/kg subcutaneously at week 0, then every other week starting at week 1, or oral methotrexate once weekly (0·1-0·4 mg/kg) for 16 weeks. Randomisation was stratified by history of etanercept treatment, with a block size of three. Responders were withdrawn from treatment (for up to 36 weeks) and re-treated with adalimumab (for 16 weeks) if disease became uncontrolled. Ranked primary efficacy endpoints were the proportion of patients who achieved at least 75% improvement from baseline in Psoriasis Area and Severity Index (PASI75) score and clear or minimal physician global assessment (PGA) score at week 16, comparing adalimumab 0·8 mg/kg with methotrexate. Efficacy analysis was by intention to treat, and safety analysis included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT01251614, and has been completed.
Between Dec 14, 2010, and Feb 5, 2015, 114 patients were randomly assigned to adalimumab 0·8 mg/kg (n=38), adalimumab 0·4 mg/kg (n=39) or methotrexate (n=37). At week 16, PASI75 was achieved in 22 (58%) of 38 patients in the adalimumab 0·8 mg/kg group compared with 12 (32%) of 37 patients in the methotrexate group (p=0·027). 23 (61%) of 38 patients in the adalimumab 0·8 mg/kg group and 15 (41%) of 37 in the methotrexate group achieved clear or minimal PGA (p=0·083). In the adalimumab 0·4 mg/kg group, 17 (44%) of 39 patients achieved PASI75 and 16 (41%) achieved clear or minimal PGA. The most frequent adverse events were infections (17 [45%] of 38 in the adalimumab 0·8 mg/kg group during initial treatment; 22 [56%] of 39 in the adalimumab 0·4 mg/kg group; 21 [57%] of 37 in the methotrexate group). Three serious adverse events were reported, all in patients in the adalimumab 0·4 mg/kg group, and were not judged to be related to study drug.
Treatment with adalimumab 0·8 mg/kg in children and adolescents with severe plaque psoriasis provided significant improvements in PASI75 and a non-significant increase in the proportion of patients who achieved clear or minimal PGA compared with methotrexate. No new safety risks were identified.
AbbVie.
阿达木单抗适用于治疗成人中度至重度斑块状银屑病。我们评估了阿达木单抗在严重斑块状银屑病儿童和青少年患者中的疗效和安全性。
这是一项在 13 个国家的 38 家诊所进行的随机、双盲、多周期、3 期临床试验。纳入未接受过局部治疗且病情严重的斑块状银屑病患者（年龄≥4 岁且＜18 岁），采用交互式语音或网络应答系统（1:1:1）随机分配，接受阿达木单抗 0.8mg/kg 或 0.4mg/kg 皮下注射，分别于第 0 周和第 1 周开始每两周一次，或每周一次口服甲氨蝶呤（0.1-0.4mg/kg），共 16 周。根据既往是否接受过依那西普治疗进行分层随机化，分组大小为 3 个。如果疾病失去控制，应答者将停止治疗（最多 36 周），然后重新接受阿达木单抗治疗（16 周）。主要疗效终点是第 16 周时达到至少 75%改善的患者比例，包括患者的银屑病面积和严重程度指数（PASI75）评分和医生整体评估（PGA）评分达到清晰或几乎无，比较阿达木单抗 0.8mg/kg 与甲氨蝶呤。疗效分析采用意向治疗，安全性分析包括接受至少一剂研究药物的所有患者。本试验在 ClinicalTrials.gov 注册，编号为 NCT01251614，已经完成。
2010 年 12 月 14 日至 2015 年 2 月 5 日，纳入 114 名患者随机分配至阿达木单抗 0.8mg/kg 组（n=38）、阿达木单抗 0.4mg/kg 组（n=39）或甲氨蝶呤组（n=37）。第 16 周时，阿达木单抗 0.8mg/kg 组 38 名患者中有 22 名（58%）达到 PASI75，而甲氨蝶呤组 37 名患者中只有 12 名（32%）达到 PASI75（p=0.027）。阿达木单抗 0.8mg/kg 组 38 名患者中有 23 名（61%）和甲氨蝶呤组 37 名患者中有 15 名（41%）达到了清晰或几乎无 PGA（p=0.083）。阿达木单抗 0.4mg/kg 组 39 名患者中有 17 名（44%）达到 PASI75，16 名（41%）达到清晰或几乎无 PGA。最常见的不良反应是感染（阿达木单抗 0.8mg/kg 组在初始治疗期间为 38 名患者中的 17 名[45%]；阿达木单抗 0.4mg/kg 组为 39 名患者中的 22 名[56%]；甲氨蝶呤组为 37 名患者中的 21 名[57%]）。报告了 3 例严重不良事件，均发生在阿达木单抗 0.4mg/kg 组的患者中，且均未被认为与研究药物有关。
与甲氨蝶呤相比，阿达木单抗 0.8mg/kg 治疗严重斑块状银屑病儿童和青少年患者可显著改善 PASI75，且达到清晰或几乎无 PGA 的患者比例略有增加。未发现新的安全风险。
艾伯维。
