Thom Howard, Cheng Vincent, Keeney Edna, Neary Maureen P, Eccleston Anthony, Zang Chuanbo, Cappelleri Joseph C, Cha Amy, Thyssen Jacob P
Bristol Medical School, University of Bristol, Bristol, UK.
Clifton Insight, Bristol, UK.
Dermatol Ther (Heidelb). 2022 Jan;12(1):185-194. doi: 10.1007/s13555-021-00646-1. Epub 2021 Dec 8.
Crisaborole topical ointment, 2%, is a nonsteroidal, topical anti-inflammatory phosphodiesterase-4 (PDE4) inhibitor that is approved for the treatment of mild-to-moderate atopic dermatitis (AD). The objective of the current analysis was to compare the efficacy of crisaborole 2% relative to pimecrolimus 1%, tacrolimus 0.03% and tacrolimus 0.1% in patients aged ≥ 2 years with mild-to-moderate AD by comparing improvement in Investigator's Static Global Assessment scores ( (ISGA scores of 0/1 indicating "clear or almost clear"). ISGA was selected as the primary efficacy outcome given the US Food and Drug Administration's recommendations on the use of ISGA for assessment of global severity in AD and to align with efficacy measurements in the crisaborole registration trials. Safety endpoints could not be analyzed due to differences in outcome definitions across studies.
Efficacy of crisaborole was evaluated using individual patient data (IPD) from two pivotal phase III randomized controlled trials (RCTs), and efficacy of comparators was evaluated using published RCTs included in a previous network meta-analysis. Vehicle controls were not comparable due to differences in ingredients and population imbalance and, therefore, an unanchored matching-adjusted indirect comparison (MAIC) was used, which reweighted IPD for crisaborole to estimate absolute response in comparator populations.
The odds of achieving an improvement in ISGA score was higher with crisaborole 2% versus pimecrolimus 1% (odds ratio [OR] 2.03; 95% confidence interval [CI] 1.45-2.85; effective sample size = 627, reduced from 1021; p value < 0.001) and for crisaborole 2% versus tacrolimus 0.03% (OR 1.50; 95% CI 1.09-2.05; effective sample size = 311, reduced from 1021; p = 0.012).
The unanchored MAIC suggests that the odds of achieving an improvement in ISGA score is greater with crisaborole 2% than with pimecrolimus 1% or tacrolimus 0.03% in patients aged ≥ 2 years with mild-to-moderate AD. These results are consistent with findings from the previously published network meta-analysis, which used a different methodology for performing indirect treatment comparisons.
2%的克立硼罗外用软膏是一种非甾体类外用抗炎磷酸二酯酶-4（PDE4）抑制剂，已被批准用于治疗轻至中度特应性皮炎（AD）。本分析的目的是通过比较研究者静态整体评估评分（ISGA评分为0/1表示“清除或几乎清除”）的改善情况，比较2%克立硼罗与1%吡美莫司、0.03%他克莫司和0.1%他克莫司在≥2岁轻至中度AD患者中的疗效。鉴于美国食品药品监督管理局关于使用ISGA评估AD全球严重程度的建议，并与克立硼罗注册试验中的疗效测量方法保持一致，ISGA被选为主要疗效指标。由于各研究结果定义不同，无法分析安全性终点。
使用两项关键的III期随机对照试验（RCT）的个体患者数据（IPD）评估克立硼罗的疗效，使用先前网络荟萃分析中纳入的已发表RCT评估对照药物的疗效。由于成分差异和人群不平衡，赋形剂对照不具可比性，因此采用了无锚定匹配调整间接比较（MAIC），对克立硼罗的IPD进行重新加权，以估计对照人群中的绝对反应。
2%克立硼罗组ISGA评分改善的几率高于1%吡美莫司组（优势比[OR]2.03；95%置信区间[CI]1.45-2.85；有效样本量=627，从1021减少；p值<0.001），2%克立硼罗组高于0.03%他克莫司组（OR 1.50；95%CI 1.09-2.05；有效样本量=311，从1021减少；p=0.012）。
无锚定MAIC表明，在≥2岁轻至中度AD患者中，2%克立硼罗组ISGA评分改善几率高于1%吡美莫司组或0.03%他克莫司组。这些结果与先前发表的网络荟萃分析结果一致，该分析采用了不同的方法进行间接治疗比较。
