Department of Dermatology, Oregon Health & Science University, Portland, Oregon.
Department of Dermatology, Yale University, New Haven, Connecticut.
JAMA Dermatol. 2020 Jun 1;156(6):668-675. doi: 10.1001/jamadermatol.2020.0932.
Pityriasis rubra pilaris is a rare and disabling cutaneous disease that is frequently recalcitrant to conventional therapies and appears to involve interleukin (IL)-17 overexpression.
To investigate the clinical response and safety of ixekizumab in treating pityriasis rubra pilaris.
DESIGN, SETTING, AND PARTICIPANTS: Single-arm, investigator-initiated trial conducted in adult patients with moderate to severe pityriasis rubra pilaris at a single-center academic university from June 2018 to January 2020. A total of 41 patients were screened, 12 were enrolled, and 11 completed the full duration of therapy. A referred, consecutive sample was used during participant selection. The treatment period and primary outcome occurred over 24 weeks with additional patient follow-up through 36 weeks.
Subcutaneous administration of ixekizumab, a humanized IgG4 antibody that binds IL-17A, at the US Food and Drug Administration-approved dosing schedule for treatment of psoriasis for 24 weeks.
The primary outcome was the mean change in Psoriasis Area and Severity Index at 24 weeks. Secondary outcomes included change in affected body surface area, quality of life, induction of sustained remission, and association of improvement with CARD14 genetic variations and cutaneous cytokine expression.
A total of 12 white patients (mean [SD] age, 49.8 [15.1] years; 8 male [67%]) were enrolled between June 2018 and April 2019, with 11 completing the full course of intervention. The mean (SEM) improvements in Psoriasis Area and Severity Index, affected body surface area, and Dermatology Life Quality Index were 15.2 (2.1) (P < .0001), 29.8% (9.3%) (P = .009), and 9.5 (2.5) (P = .004), respectively. The 4 participants with the most improvement in Psoriasis Area and Severity Index at week 24 stayed in remission at week 36 (defined as lack of increase in Psoriasis Area and Severity Index from week 24 through week 36), off therapy. Relative dermal IL-17A expression decreased by a 1.9 log-fold change. No participants had known pathogenic CARD14 variations. There were no serious adverse events.
In this single-armed trial, ixekizumab was associated with reduced clinical signs and symptoms of pityriasis rubra pilaris in a subset of patients, including those in whom other systemic therapies have failed.
ClinicalTrials.gov Identifier: NCT03485976.
红皮病性银屑病是一种罕见且使人致残的皮肤疾病，常对常规治疗有抗药性，似乎与白细胞介素（IL）-17 过度表达有关。
研究依奇珠单抗治疗红皮病性银屑病的临床疗效和安全性。
设计、地点和参与者：这是一项在 2018 年 6 月至 2020 年 1 月期间于一家学术型大学中心进行的、单臂、研究者发起的临床试验，纳入了中度至重度红皮病性银屑病的成年患者。共有 41 名患者接受了筛选，其中 12 名入组，11 名完成了整个治疗疗程。在选择患者时使用了经转诊的连续样本。治疗期和主要结局在 24 周内进行，在 36 周时对患者进行了额外的随访。
根据美国食品和药物管理局批准的治疗银屑病的剂量方案，对患者进行皮下注射依奇珠单抗，这是一种与人 IgG4 抗体结合的白细胞介素-17A。
24 周时的银屑病面积和严重程度指数的平均变化。次要结局指标包括受影响的体表面积、生活质量、诱导持续缓解的情况，以及改善与 CARD14 遗传变异和皮肤细胞因子表达的关系。
共有 12 名白人患者（平均[标准差]年龄为 49.8[15.1]岁；8 名男性[67%]）于 2018 年 6 月至 2019 年 4 月入组，其中 11 名完成了整个干预疗程。银屑病面积和严重程度指数、受影响的体表面积和皮肤病生活质量指数的平均（SEM）改善分别为 15.2（2.1）（P < .0001）、29.8%（9.3%）（P = .009）和 9.5（2.5）（P = .004）。在第 24 周时，银屑病面积和严重程度指数改善最明显的 4 名患者在第 36 周时仍处于缓解期（定义为从第 24 周至第 36 周，银屑病面积和严重程度指数无增加），无需治疗。相对皮肤内的白细胞介素-17A 表达减少了 1.9 对数倍。没有患者存在已知的致病性 CARD14 变异。没有发生严重不良事件。
在这项单臂试验中，依奇珠单抗在一组患者中与减少红皮病性银屑病的临床体征和症状有关，包括那些对其他全身治疗无效的患者。
ClinicalTrials.gov 标识符：NCT03485976。
