比较布罗达芦单抗与乌司奴单抗治疗银屑病的 3 期研究。

Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis.

机构信息

From the Icahn School of Medicine at Mount Sinai, New York (M.L., L.K.); University of Connecticut School of Medicine, Farmington (B.S.); Probity Medical Research (B.S., L.S., D.T.) and XLR8 Medical Research (D.T.), Windsor, ON, K Papp Medical Research (K.P.), Waterloo, ON, and Dalhousie University, Halifax, NS (R.G.L.) - all in Canada; Baylor University Medical Center, Dallas (A.M.); Northwestern University, Feinberg School of Medicine, Chicago (K.G.); Niepubliczny Zakład Opieki Zdrowotnej multiMedica, Wrocław (J.W.), and Lubelskie Centrum Diagnostyczne, Świdnik (T.B.) - both in Poland; Hospital de la Santa Creu i Sant Pau, Barcelona (L.P.); Veracity Clinical Research, Woolloongabba, QLD, Australia (L.S.); Florida Academic Dermatology Center, Miami (F.K.); University of Colorado, Denver (A.W.A.); Medizinische Universität Wien, Vienna, Austria (G.S.); Massachusetts General Hospital and Harvard Medical School, Boston (A.B.K.); Sorbonne Paris Cité Université Paris Diderot, Assistance Publique-Hôpitaux de Paris Hôpital Saint Louis, Paris (H.B.), Paul Sabatier University, Toulouse (C.P.), and University Hospital of Nice, Nice (J.-P.L.) - all in France; Kaiser Permanente Los Angeles Medical Center, Los Angeles (J.J.W.), Bakersfield Dermatology and Skin Cancer Medical Group, Bakersfield (J.C.), University of California, San Francisco, San Francisco (J.K.), and Amgen, Thousand Oaks (G.A., J.L., W.S., C.E.M., Y.S., N.E., P.K., B.K., A.N.) - all in California.; University of Texas Health Science Center, Houston (S.T.); DermResearch, Louisville, KY (L.K.); University of Rome Tor Vergata, Rome (S.C.); University of Utah Medical Center, Salt Lake City (K.C.D.); and the Psoriasis Treatment Center of Central New Jersey, East Windsor (J.B.).

出版信息

N Engl J Med. 2015 Oct;373(14):1318-28. doi: 10.1056/NEJMoa1503824.

DOI:10.1056/NEJMoa1503824

PMID:26422722

Abstract

BACKGROUND

Early clinical studies suggested that the anti-interleukin-17 receptor A monoclonal antibody brodalumab has efficacy in the treatment of psoriasis.

METHODS

In two phase 3 studies (AMAGINE-2 and AMAGINE-3), patients with moderate-to-severe psoriasis were randomly assigned to receive brodalumab (210 mg or 140 mg every 2 weeks), ustekinumab (45 mg for patients with a body weight ≤100 kg and 90 mg for patients >100 kg), or placebo. At week 12, patients receiving brodalumab were randomly assigned again to receive a brodalumab maintenance dose of 210 mg every 2 weeks or 140 mg every 2 weeks, every 4 weeks, or every 8 weeks; patients receiving ustekinumab continued to receive ustekinumab every 12 weeks, and patients receiving placebo received 210 mg of brodalumab every 2 weeks. The primary aims were to evaluate the superiority of brodalumab over placebo at week 12 with respect to at least a 75% reduction in the psoriasis area-and-severity index score (PASI 75) and a static physician's global assessment (sPGA) score of 0 or 1 (clear or almost clear skin), as well as the superiority of brodalumab over ustekinumab at week 12 with respect to a 100% reduction in PASI score (PASI 100).

RESULTS

At week 12, the PASI 75 response rates were higher with brodalumab at the 210-mg and 140-mg doses than with placebo (86% and 67%, respectively, vs. 8% [AMAGINE-2] and 85% and 69%, respectively, vs. 6% [AMAGINE-3]; P<0.001); the rates of sPGA scores of 0 or 1 were also higher with brodalumab (P<0.001). The week 12 PASI 100 response rates were significantly higher with 210 mg of brodalumab than with ustekinumab (44% vs. 22% [AMAGINE-2] and 37% vs. 19% [AMAGINE-3], P<0.001). The PASI 100 response rates with 140 mg of brodalumab were 26% in AMAGINE-2 (P=0.08 for the comparison with ustekinumab) and 27% in AMAGINE-3 (P=0.007). Rates of neutropenia were higher with brodalumab and with ustekinumab than with placebo. Mild or moderate candida infections were more frequent with brodalumab than with ustekinumab or placebo. Through week 52, the rates of serious infectious episodes were 1.0 (AMAGINE-2) and 1.3 (AMAGINE-3) per 100 patient-years of exposure to brodalumab.

CONCLUSIONS

Brodalumab treatment resulted in significant clinical improvements in patients with moderate-to-severe psoriasis. (Funded by Amgen; AMAGINE-2 and AMAGINE-3 ClinicalTrials.gov numbers, NCT01708603 and NCT01708629.).

摘要

背景

早期临床研究表明，抗白细胞介素-17 受体 A 单克隆抗体 brodalumab 在治疗银屑病方面具有疗效。

方法

在两项 3 期研究（AMAGINE-2 和 AMAGINE-3）中，中度至重度银屑病患者被随机分配接受 brodalumab（210 mg 或 140 mg，每 2 周）、ustekinumab（体重≤100 kg 的患者给予 45 mg，体重>100 kg 的患者给予 90 mg）或安慰剂治疗。在第 12 周，接受 brodalumab 的患者再次随机分配接受 brodalumab 维持剂量 210 mg，每 2 周或每 4 周或每 8 周；接受 ustekinumab 的患者继续每 12 周接受 ustekinumab，接受安慰剂的患者每 2 周接受 210 mg brodalumab。主要目的是评估与安慰剂相比，brodalumab 在第 12 周时在至少 75%的银屑病面积和严重程度指数评分（PASI 75）和静态医师整体评估（sPGA）评分 0 或 1（清除或几乎清除皮肤）方面的优越性，以及与 ustekinumab 相比，brodalumab 在第 12 周时在 PASI 评分 100%（PASI 100）方面的优越性。

结果

在第 12 周时，与安慰剂相比，brodalumab 210 mg 和 140 mg 剂量的 PASI 75 应答率更高（分别为 86%和 67%，vs. 8%[AMAGINE-2]和 85%和 69%，vs. 6%[AMAGINE-3]；P<0.001）；sPGA 评分 0 或 1 的比率也更高（P<0.001）。与 ustekinumab 相比，210 mg brodalumab 的第 12 周 PASI 100 应答率显著更高（44% vs. 22%[AMAGINE-2]和 37% vs. 19%[AMAGINE-3]；P<0.001）。在 AMAGINE-2 中，140 mg brodalumab 的 PASI 100 应答率为 26%（与 ustekinumab 相比，P=0.08），在 AMAGINE-3 中为 27%（P=0.007）。与安慰剂相比，brodalumab 和 ustekinumab 的中性粒细胞减少发生率更高。与 ustekinumab 或安慰剂相比，brodalumab 更频繁出现轻度或中度念珠菌感染。在第 52 周时，brodalumab 的严重感染事件发生率为每 100 患者-年 1.0（AMAGINE-2）和 1.3（AMAGINE-3）。