Probity Medical Research, Waterloo, ON, Canada.
Medical College of Wisconsin, Milwaukee, WI, U.S.A.
Br J Dermatol. 2018 Aug;179(2):320-328. doi: 10.1111/bjd.16464. Epub 2018 May 23.
Biologics are being used increasingly to treat moderate-to-severe psoriasis. Efficacy may differ in patients with previous exposure to biologics.
To investigate the impact of previous biologic exposure on the efficacy and safety of brodalumab and ustekinumab in patients with moderate-to-severe plaque psoriasis.
Two placebo- and ustekinumab-controlled phase III clinical trials. There was an initial 12-week induction phase where patients were treated with brodalumab [210 mg or 140 mg every 2 weeks (Q2W)], ustekinumab or placebo. Efficacy end points included ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) and static Physician's Global Assessment (score of 0 or 1) vs. placebo, PASI 100 vs. ustekinumab, Dermatology Life Quality Index and Psoriasis Symptom Inventory. Adverse events were monitored throughout.
In total, 493 patients [334 (27%) brodalumab 210 mg Q2W and 159 (26%) ustekinumab] had received prior biologics; 150 (12%) and 62 (10%), respectively, reported previously failed treatment with a biologic. Brodalumab efficacy in patients with or without previous exposure to biologics was statistically equivalent: 40·9% and 39·5% of biologic-naive and -experienced patients achieved PASI 100 at week 12, compared with 21·1% and 17·0% with ustekinumab (both P < 0·001). In patients where prior biologics had been successful or failed, 41·7% and 32·0% achieved PASI 100, compared with 21·1% and 11·3% with ustekinumab. Tolerability was similar, and did not appear to be influenced by previous treatment with biologics.
The efficacy of brodalumab 210 mg Q2W was similar regardless of prior biological therapy (P = 0·31, 0·32 and 0·64 for PASI 75, 90 and 100, respectively). Almost twice as many patients achieved PASI 100 or complete clearance with brodalumab at week 12 compared with ustekinumab; the differences were most noticeable where previous biologics had failed. Both treatments were well tolerated.
生物制剂越来越多地用于治疗中重度银屑病。既往接受过生物制剂治疗的患者，其疗效可能存在差异。
旨在探究在中重度斑块状银屑病患者中，既往使用生物制剂对布罗达umab 和乌司奴单抗疗效和安全性的影响。
两项安慰剂和乌司奴单抗对照的 III 期临床试验。在为期 12 周的诱导期，患者接受布罗达umab（210mg 或 140mg，每 2 周一次[Q2W]）、乌司奴单抗或安慰剂治疗。疗效终点包括与安慰剂相比，银屑病面积和严重程度指数（PASI75）改善≥75%和静态医师整体评估（评分 0 或 1）、与乌司奴单抗相比，PASI100、皮肤病生活质量指数和银屑病症状自评量表。整个过程中均监测不良事件。
共有 493 名患者[334 名（27%）接受布罗达umab 210mg Q2W 和 159 名（26%）接受乌司奴单抗]既往接受过生物制剂治疗；分别有 150 名（12%）和 62 名（10%）患者报告此前曾接受过生物制剂治疗失败。既往接受或未接受生物制剂治疗的患者，布罗达umab 的疗效相当：第 12 周时，生物制剂初治和治疗失败患者的 PASI100 分别为 40.9%和 39.5%，而乌司奴单抗组分别为 21.1%和 17.0%（均 P＜0.001）。既往生物制剂治疗成功或失败的患者中，分别有 41.7%和 32.0%达到 PASI100，而乌司奴单抗组分别为 21.1%和 11.3%。两种药物的耐受性相似，且似乎不受既往生物治疗的影响。
无论既往接受何种生物治疗，布罗达umab 210mg Q2W 的疗效均相似（P=0.31、0.32 和 0.64 时，PASI75、90 和 100 的缓解率分别为 41.7%、32.0%和 21.1%）。第 12 周时，与乌司奴单抗相比，接受布罗达umab 治疗的患者有近两倍的患者达到 PASI100 或完全清除；在既往生物制剂治疗失败的患者中，差异最为显著。两种治疗均具有良好的耐受性。
