Department of Dermatology, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Rheumatology, Sint Maartenskliniek, Nijmegen, the Netherlands.
JAMA Dermatol. 2020 Apr 1;156(4):393-400. doi: 10.1001/jamadermatol.2019.4897.
Biologics revolutionized the treatment of psoriasis. Biologics are given in a fixed dose, but lower doses might be possible.
To investigate whether dose reduction (DR) of biologics in patients with stable psoriasis is noninferior to usual care (UC).
DESIGN, SETTING, AND PARTICIPANTS: This pragmatic, open-label, prospective, controlled, noninferiority randomized clinical trial was conducted from March 1, 2016, to July 22, 2018, at 6 dermatology departments in the Netherlands. A total of 120 patients with plaque psoriasis and stable low disease activity who were receiving treatment with adalimumab, etanercept, or ustekinumab were studied.
Patients were randomized 1:1 to DR (n = 60) or UC (n = 60). In the DR group, injection intervals were prolonged stepwise, leading to 67% and 50% of the original dose.
The primary outcome was between-group difference in disease activity corrected for baseline at 12 months compared with the predefined noninferiority margin of 0.5. Secondary outcomes were Psoriasis Area and Severity Index (PASI) score and health-related quality of life (including Dermatology Life Quality Index [DLQI] and Medical Outcomes Study 36-Item Short Form Health Survey scores), proportion of patients with short and persistent flares (defined as PASI and/or DLQI scores >5 for ≥3 months), and proportion of patients with successful dose tapering.
Of 120 patients (mean [SD] age, 54.0 [13.2] years; 82 [68%] male), 2 patients were lost to follow-up, 2 patients had a protocol violation, and 5 patients had a protocol deviation, leaving 111 patients for the per-protocol analysis (53 in the DR group and 58 in the UC group). The median PASI scores at month 12 were 3.4 (interquartile range [IQR], 2.2-4.5) in the DR group and 2.1 (IQR, 0.6-3.6) in the UC group (mean difference, 1.2; 95% CI, 0.7-1.8). This indicates that noninferiority was not demonstrated for DR compared to UC. The median DLQI score at month 12 was 1.0 (IQR, 0.0-2.0) in the DR group and 0.0 (IQR, 0.0-2.0) in the UC group (mean difference, 0.8; 95% CI, 0.3-1.3), indicating noninferiority for DR compared with UC. No significant difference was found regarding persistent flares between groups (n = 5 in both groups). Twenty-eight patients (53%; 95% CI, 39%-67%) in the DR group tapered their dose successfully at 12 months. No severe adverse events related to the intervention occurred.
In this trial, noninferiority was not demonstrated for DR of adalimumab, etanercept, and ustekinumab based on the PASI in patients with psoriasis compared with UC with the chosen noninferiority margin. However, the strategy was noninferior based on the DLQI. Dose tapering did not lead to persistent flares or safety issues.
ClinicalTrials.gov Identifier: NCT02602925.
重要性：生物制剂彻底改变了银屑病的治疗方法。生物制剂采用固定剂量给药，但可能需要降低剂量。
目的：研究在病情稳定的银屑病患者中，生物制剂的剂量减少（DR）是否不劣于常规护理（UC）。
设计、设置和参与者：这是一项从 2016 年 3 月 1 日至 2018 年 7 月 22 日在荷兰 6 个皮肤科部门进行的务实、开放标签、前瞻性、对照、非劣效性随机临床试验。共纳入 120 例接受阿达木单抗、依那西普或乌司奴单抗治疗、斑块状银屑病且病情稳定、低疾病活动度的患者。
干预措施：患者以 1:1 的比例随机分为 DR 组（n=60）或 UC 组（n=60）。在 DR 组中，注射间隔逐渐延长，导致原始剂量的 67%和 50%。
主要结局和测量：主要结局为与基线相比，12 个月时两组间疾病活动度的差异，与预先设定的非劣效性边界为 0.5。次要结局包括银屑病面积和严重程度指数（PASI）评分和健康相关生活质量（包括皮肤病生活质量指数[DLQI]和医疗结果研究 36 项简短健康调查评分），短持续时间发作（定义为 PASI 和/或 DLQI 评分 >5 持续 ≥3 个月）的患者比例，以及成功剂量递减的患者比例。
结果：在 120 例患者（平均[SD]年龄，54.0[13.2]岁；82[68%]男性）中，2 例患者失访，2 例患者违反方案，5 例患者方案偏离，111 例患者纳入符合方案分析（DR 组 53 例，UC 组 58 例）。DR 组和 UC 组患者在第 12 个月的 PASI 中位数分别为 3.4（四分位距[IQR]，2.2-4.5）和 2.1（IQR，0.6-3.6）（平均差异，1.2；95%置信区间，0.7-1.8）。这表明 DR 与 UC 相比，非劣效性未得到证实。DR 组和 UC 组在第 12 个月的 DLQI 中位数分别为 1.0（IQR，0.0-2.0）和 0.0（IQR，0.0-2.0）（平均差异，0.8；95%置信区间，0.3-1.3），表明 DR 与 UC 相比具有非劣效性。两组间持续性发作无显著差异（两组均为 5 例）。28 例（53%；95%置信区间，39%-67%）患者在 12 个月时成功减少了剂量。未发生与干预相关的严重不良事件。
结论和相关性：在这项试验中，与 UC 相比，基于 PASI，在银屑病患者中，DR 阿达木单抗、依那西普和乌司奴单抗不劣效，但基于 DLQI 则是等效的。剂量递减不会导致持续性发作或安全性问题。
试验注册：ClinicalTrials.gov 标识符：NCT02602925。
