Canakinumab in adults with steroid-refractory pyoderma gangrenosum
Canakinumab in adults with steroid-refractory pyoderma gangrenosum
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DOI：
10.1111/bjd.14037
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发表时间：
2015-11-01
影响因子：
10.3
通讯作者：
French, L. E.
中科院分区：
文献类型：
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作者：
Kolios, A. G. A.;Maul, J. -T.;French, L. E.
背景 坏疽性脓皮病 (PG) 是一种罕见的中性粒细胞性溃疡性皮肤病，很难治疗，尤其是在对类固醇无反应的情况下。目的 确定卡那单抗是否是一种有效且安全的治疗 PG 的方法。方法 5 名临床和组织学证实的类固醇难治性 PG 成年患者参加了这项前瞻性开放标签研究。他们在第 0 周皮下注射卡那奴单抗 150 mg，如果反应不充分，可在第 2 周接受 150 mg 皮下注射 [医师总体评估 (PGA) >= 2]，并根据 PGA 在第 8 周接受 150-300 mg 可选注射。主要临床终点是第16周时临床改善（PGA至少-1）和/或完全缓解（PGA 0或1）。对皮肤样本进行实时定量聚合酶链反应以量化细胞因子mRNA水平。结果白细胞介素（IL）-1β及其已知靶基因IL6、CXCL8和IL36A在PG病变皮肤中显着增加。在卡那单抗治疗下，五名患者中有四名出现靶病灶大小、PGA 和皮肤病生活质量指数 (DLQI) 下降，五名患者中的三名达到完全缓解。目标病灶的平均直径从第 1 次就诊时的 4.32 +/- 2.6 cm 减少到第 7 次就诊时的 0.78 +/- 1.3 cm (P = 0.03)。平均 DLQI 从第 1 次就诊时的 15.5 下降到第 7 次就诊时的 8 +/- 4 (P = 0.01)。两名患者报告了不良反应：一名患者疲劳，另一名患者非目标病变疾病恶化。结论我们的数据表明，IL-1β 在 PG 中发挥关键致病作用，卡那奴单抗可能代表类固醇难治性 PG 的治疗选择。
Background Pyoderma gangrenosum (PG) is a rare, neutrophilic, ulcerative skin disease that is difficult to treat, especially when unresponsive to steroids. Objectives To determine whether canakinumab is an effective and safe treatment in PG.Methods Five adult patients with clinically and histologically confirmed steroid-refractory PG were enrolled in this prospective open-label study. They received canakinumab 150 mg subcutaneously at week 0 with an optional 150 mg at week 2 in case of an inadequate response [Physician's Global Assessment (PGA) >= 2], and an optional 150-300 mg at week 8 depending on PGA. The primary clinical end point was clinical improvement (PGA at least -1 from baseline) and/or complete remission (PGA 0 or 1) at week 16. Real-time quantitative polymerase chain reaction was performed on skin samples to quantify cytokine mRNA levels.Results Interleukin (IL)-1 beta and its known target genes IL6, CXCL8 and IL36A were significantly increased in lesional skin of PG. Under canakinumab therapy, four of five patients showed a decrease in target-lesion size, PGA and Dermatology Life Quality Index (DLQI), and three of five achieved complete remission. The mean diameter of target lesions decreased from 4.32 +/- 2.6 cm at visit 1 to 0.78 +/- 1.3 cm at visit 7 (P = 0.03). Mean DLQI decreased from 15.5 at visit 1 to 8 +/- 4 by visit 7 (P = 0.01). Adverse effects were reported in two patients: fatigue in one and worsening of disease at a nontarget lesion in the other.Conclusions Our data indicate that IL-1 beta plays a key pathogenic role in PG and canakinumab may represent a therapeutic option for steroid-refractory PG.