Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, and Skinflammation® Center, Hamburg, Germany.
Department of Dermatology, University Hospital Essen, Essen, Germany.
Br J Dermatol. 2021 May;184(5):849-856. doi: 10.1111/bjd.19398. Epub 2020 Nov 18.
Secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin-17A and shows long-lasting efficacy and safety in plaque psoriasis. More evidence is required to optimize secukinumab dosing according to clinical response.
GAIN compared the efficacy and safety of secukinumab 300 mg every 2 weeks (q2w) with 300 mg every 4 weeks (q4w) in patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) but not PASI 90 after 16 weeks.
In total, 772 patients with moderate-to-severe plaque psoriasis received secukinumab 300 mg subcutaneously at baseline and weeks 1, 2, 3 and 4, then q4w until week 16. At week 16, patients with PASI ≥ 75 to PASI < 90 were randomized 1: 1 to continue q4w dosing (n = 162) or switch to q2w (n = 163) to week 32. The primary endpoint was superiority of q2w to q4w dosing for PASI 90 response at week 32.
PASI 90 response at week 32 was numerically greater with secukinumab 300 mg q2w than with secukinumab 300 mg q4w in suboptimal responders, but this did not reach statistical significance (64·4% vs. 57·4%; odds ratio 0·64, 95% confidence interval 0·39-1·07; P = 0·087). Although the primary endpoint was not met, absolute PASI was significantly lower at week 32 in q2w vs. q4w patients (2·11 vs. 2·84, P = 0·024). Significantly more patients with q2w vs. q4w dosing showed minimal disease activity (Investigator's Global Assessment score 0 or 1: 73·0% vs. 64·1%, P < 0·05) and improved quality of life (Dermatology Life Quality Index score 0 or 1: 58·9% vs. 50·6%, P < 0·05) at week 32. No new or unexpected safety signals arose.
Most patients achieved PASI 90 response with secukinumab q4w. There was potential benefit of q2w dosing in some suboptimal responders. Continued q4w treatment can improve response even after 16 weeks.
司库奇尤单抗是一种全人源单克隆抗体，能选择性中和白细胞介素-17A，在斑块状银屑病患者中显示出持久的疗效和安全性。需要更多证据来根据临床反应优化司库奇尤单抗的剂量。
GAIN 研究比较了司库奇尤单抗 300mg 每 2 周（q2w）与每 4 周（q4w）治疗在第 16 周达到银屑病面积和严重程度指数（PASI）≥75%改善但未达到 PASI90 的患者中的疗效和安全性。
共有 772 例中重度斑块状银屑病患者在基线和第 1、2、3、4 周接受司库奇尤单抗 300mg 皮下注射，然后 q4w 至第 16 周。在第 16 周时，PASI≥75%但＜90%的患者被随机 1：1分为继续 q4w 治疗组（n=162）或转换为 q2w 治疗组（n=163）至第 32 周。主要终点为第 32 周时 q2w 优于 q4w 治疗的 PASI90 应答。
在应答欠佳的患者中，司库奇尤单抗 300mg q2w 组的 PASI90 应答率在数值上高于司库奇尤单抗 300mg q4w 组，但未达到统计学意义（64.4% vs. 57.4%；优势比 0.64，95%置信区间 0.39-1.07；P=0.087）。尽管主要终点未达到，但 q2w 组在第 32 周时的绝对 PASI 明显低于 q4w 组（2.11 vs. 2.84，P=0.024）。与 q4w 组相比，更多的 q2w 组患者表现出疾病最小活动度（研究者全球评估评分 0 或 1：73.0% vs. 64.1%，P＜0.05）和改善的生活质量（皮肤病生活质量指数评分 0 或 1：58.9% vs. 50.6%，P＜0.05）。第 32 周时没有出现新的或意外的安全性信号。
大多数患者在 q4w 治疗时达到 PASI90 应答，在部分应答欠佳的患者中，q2w 剂量有潜在获益。即使在第 16 周后继续 q4w 治疗也可以提高应答率。
