Department of Dermatology, Radboud University, Nijmegen, the Netherlands.
Department of Dermatology, Northwestern University, Chicago, Illinois.
JAMA Dermatol. 2020 Apr 1;156(4):384-392. doi: 10.1001/jamadermatol.2019.4835.
Few studies have compared the use of methotrexate and biologics, the most commonly used systemic medications for treatment of moderate to severe psoriasis in children.
To assess the real-world, 6-month reduction in psoriasis severity and long-term drug survival (rate and duration of adherence to a specific drug) of methotrexate vs biologics in plaque psoriasis in children.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective medical records review was conducted at 20 European and North American centers. Treatment response was based on site-reported Psoriasis Area and Severity Index (PASI) and/or Physician Global Assessment (PGA) scores at baseline and within the first 6 months of treatment. Participants included all 234 consecutively seen children with moderate to severe psoriasis who received at least 3 months of methotrexate or biologics from December 1, 1990, to September 16, 2014, with sufficient data for analysis. Data analysis was performed from December 14, 2015, to September 1, 2016.
PASI, with a range from 0 to 72 (highest score indicating severe psoriasis), and/or PGA, with a scale of 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), and 5 (very severe).
Of 234 pediatric patients (103 boys [44.0%]; 131 girls [56.0%]) treated with methotrexate and/or biologics, 163 patients (69.7%) exclusively received methotrexate, 47 patients (20.1%) exclusively received biologics, and 24 children (10.2%) received methotrexate and biologics sequentially. Of the latter cohort, 23 children were treated initially with methotrexate. Mean (SD) age at initiation was 11.6 (3.7) years for methotrexate and 13.3 (2.9) years for biologics (73.2% for etanercept) (P = .002). Among patients evaluated by a scoring method at 6-month follow-up, 75% or greater improvement in PASI (PASI75) was achieved in 12 of 30 patients (40.0%) receiving methotrexate and 20 of 28 patients (71.4%) receiving biologics, and PGA was clear/almost clear (PGA 0/1) in 41 of 115 patients (35.6%) receiving methotrexate and 18 of 37 patients (48.6%) receiving biologics. Achieving PASI75 and/or PGA 0/1 between baseline and 6 months was more likely with biologics than methotrexate (PASI75: odds ratio [OR], 4.56; 95% CI, 2.02-10.27; P < .001; and PGA 0/1: OR, 2.00; 95% CI, 0.98-4.00; P = .06). Decreased mean PASI and PGA scores were associated with biologics more than with methotrexate (PASI effect, -3.13; 95% CI, -4.33 to -1.94; P < .001; and PGA effect, -0.31; 95% CI, -0.56 to -0.06; P = .02). After 1, 3, and 5 years of use, overall drug survival rates for methotrexate were 77.5%, 50.3%, and 35.9%, and for biologics, the rates were 83.4%, 64.3%, and 57.1%, respectively. Biologics were associated with a better confounder-corrected drug survival than methotrexate (hazard ratio [HR], 2.23; 95% CI, 1.21-4.10; P = .01). Discontinuation owing to lack of response was comparable (HR, 1.64; 95% CI, 0.80-3.36; P = .18).
Methotrexate and biologics appear to be associated with improvement in pediatric psoriasis, although biologics seem to be associated with greater reduction in psoriasis severity scores and higher drug survival rates than methotrexate in the real-world setting. Additional studies directly comparing these medications should be performed for confirmation.
重要性：对于儿童中度至重度银屑病，甲氨蝶呤和生物制剂是最常使用的系统性药物，鲜有研究对这两种药物的使用情况进行比较。
目的：评估儿童斑块状银屑病中，甲氨蝶呤与生物制剂在 6 个月时的银屑病严重程度降低情况以及长期药物（具体药物的依从性持续时间和比例）的存活率。
设计、地点和参与者：回顾性病历审查在 20 个欧洲和北美中心进行。根据治疗开始时和治疗开始后 6 个月的站点报告的 psoriasis area and severity index (PASI) 和/或 physician global assessment (PGA) 评分来评估治疗反应。参与者为所有 234 名连续就诊的中重度银屑病儿童，他们在 1990 年 12 月 1 日至 2014 年 9 月 16 日期间接受了至少 3 个月的甲氨蝶呤或生物制剂治疗，且有足够的数据进行分析。数据分析于 2015 年 12 月 14 日至 2016 年 9 月 1 日进行。
主要结局和测量指标：PASI，范围为 0 到 72（得分越高表示银屑病越严重），和/或 PGA，评分范围为 0（清除）、1（最小）、2（轻度）、3（中度）、4（重度）和 5（非常严重）。
结果：在接受甲氨蝶呤和/或生物制剂治疗的 234 名儿科患者（男 103 例[44.0%]；女 131 例[56.0%]）中，163 例（69.7%）患者仅接受甲氨蝶呤治疗，47 例（20.1%）患者仅接受生物制剂治疗，24 例（10.2%）患者序贯接受甲氨蝶呤和生物制剂治疗。在后一组中，有 23 例患者最初接受甲氨蝶呤治疗。开始使用甲氨蝶呤的患者平均（SD）年龄为 11.6（3.7）岁，而开始使用生物制剂的患者平均年龄为 13.3（2.9）岁（73.2%为依那西普）（P = .002）。在接受 6 个月随访的评分方法评估的患者中，12 例（40.0%）接受甲氨蝶呤治疗和 20 例（71.4%）接受生物制剂治疗的患者 PASI75（PASI75：改善 75%或更多），115 例（35.6%）接受甲氨蝶呤治疗和 37 例（48.6%）接受生物制剂治疗的患者 PGA 为 0/1（PGA 0/1：清除/几乎清除）。与甲氨蝶呤相比，生物制剂更有可能实现 PASI75 和/或 PGA 0/1（PASI75：优势比[OR]，4.56；95%置信区间[CI]，2.02-10.27；P < .001；和 PGA 0/1：OR，2.00；95% CI，0.98-4.00；P = .06）。与甲氨蝶呤相比，生物制剂与降低 PASI 和 PGA 评分更相关（PASI 效应，-3.13；95% CI，-4.33 至-1.94；P < .001；和 PGA 效应，-0.31；95% CI，-0.56 至-0.06；P = .02）。使用甲氨蝶呤 1 年、3 年和 5 年的总药物存活率分别为 77.5%、50.3%和 35.9%，而使用生物制剂的总药物存活率分别为 83.4%、64.3%和 57.1%。与甲氨蝶呤相比，生物制剂具有更好的混杂因素校正药物存活率（风险比[HR]，2.23；95% CI，1.21-4.10；P = .01）。由于缺乏反应而停药的比例相似（HR，1.64；95% CI，0.80-3.36；P = .18）。
结论和相关性：甲氨蝶呤和生物制剂似乎都能改善儿童银屑病，但在真实世界环境中，与甲氨蝶呤相比，生物制剂似乎与更显著的银屑病严重程度评分降低和更高的药物存活率相关。应进行更多直接比较这些药物的研究以进行证实。
