美国贝斯以色列女执事医疗中心Alexa B Kimball团队研究了Secukinumab治疗中重度化脓性汗腺炎的疗效与安全性。这一研究成果于2023年2月3日发表在《柳叶刀》杂志上。

对于中重度化脓性汗腺炎患者，几乎没有治疗选择。该研究旨在在两项随机试验中评估secukinomab对中重度化脓性汗腺炎患者的疗效。

SUNSHINE和SUNRISE是在40个国家的219个主要研究机构进行的相同、多中心、随机、安慰剂对照、双盲3期试验。招募18岁或以上且有能力提供书面知情同意书的患者，以及至少1年内患有中度至重度化脓性汗腺炎（定义为影响≥2个不同解剖区域的总共≥5个炎性病变）的患者。受试者还同意在研究治疗期间，在受化脓性汗腺炎病变影响的区域每日使用局部非处方防腐剂。

如果患者在基线时有20个及以上的瘘管，患有持续活动性疾病，需要使用禁止药物治疗（如全身生物免疫调节治疗、活疫苗或其他研究治疗），或符合其他排除标准，则排除患者。在两项试验中，根据治疗分配，将患者随机分配（1:1:1），每2周皮下注射300 mg secukinomab，每4周皮下注射300mg secukinoumab，或皮下注射安慰剂。

主要终点是在第16周评估的总体人群中，化脓性汗腺炎临床缓解患者的比例，定义为脓肿和炎性结节计数减少50%或更多，脓肿数量或引流瘘数量与基线相比没有增加。根据脓肿、炎性结节、引流瘘、全瘘和化脓性扁桃体炎影响区域的其他病变的数量，计算化脓性扁桃腺炎的临床缓解。根据不良事件的通用术语标准，通过评估不良事件和严重不良事件的存在来评估安全性。

2019年1月31日至2021年6月7日，676名患者接受了SUNSHINE试验的筛查，其中541名患者（80%；304名女性，237名男性，平均年龄36.1岁）被纳入分析（每2周secukinomab组181名患者占33%，每4周组180名患者占33%，安慰剂组180名受试者占33%）。在同一时期，共筛选687名患者纳入SUNRISE试验，其中543名患者（79%；306名女性和237名男性；平均年龄36.3岁）纳入分析（每2周一次的secukinomab组为180名[33%]，每4周组为180[13%]，安慰剂组为183[34%]）。

在SUNSHINE试验中，与安慰剂组（180名患者中有60.7人[34%]）相比，每2周一次的secukinumab组有明显更多的患者出现化脓性汗炎临床缓解（181名患者中有81.5人[45%]），优势比为1.8。然而，每4周一次secukinumab组（180名患者中有75.2名[42%]）和安慰剂组（优势比1.5）的患者数量没有显著差异。在SUNRISE试验中，与安慰剂组（183名患者中有57.1名[31%]）相比，每2周一次的secukinomab组（180名患者中有76.2名[42%]；优势比1.6）和每4周一次secukinoumab组（180例患者中有83.1名[46%]；优势比1.9）有明显的化脓性汗炎临床缓解。

患者缓解持续到第52周试验结束。截至第16周，SUNSHINE最常见的不良事件是头痛（每2周一次的secukinomab组有17名[9%]患者，每4周一次secukinoumab组有20名[11%]患者，安慰剂组有14名[8%]患者），SUNRISE中最常见的不良事件亦为头痛（每2周一次secukinomab组有21名[12%]患者、每4周secukinumab组有17名[9%]患者，安慰剂组有15名[8%]]患者）。截至第16周，未报告与研究相关的死亡病例。两项试验中secukinumab的安全性与之前报道的一致，未发现新的或意外的安全性发现。

研究结果表明，每2周给药一次secukinumab在临床上可有效快速地改善化脓性汗腺炎的症状和体征，具有良好的安全性，治疗持续缓解时间长达52周。

附：英文原文

Title: Secukinumab in moderate-to-severe hidradenitis suppurativa (SUNSHINE and SUNRISE): week 16 and week 52 results of two identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials

Author: Alexa B Kimball, Gregor B E Jemec, Afsaneh Alavi, Ziad Reguiai, Alice B Gottlieb, Falk G Bechara, Carle Paul, Evangelos J Giamarellos Bourboulis, Axel P Villani, Andreas Schwinn, Franziska Ruff, Larisha Pillay Ramaya, Adam Reich, Ines Lobo, Rodney Sinclair, Thierry Passeron, Antonio Martorell, Pedro Mendes-Bastos, Georgios Kokolakis, Pierre-Andre Becherel, Magdalena B Wozniak, Angela Llobet Martinez, Xiaoling Wei, Lorenz Uhlmann, Anna Passera, Deborah Keefe, Ruvie Martin, Clarice Field, Li Chen, Marc Vandemeulebroecke, Shoba Ravichandran, Elisa Muscianisi

Issue&Volume: 2023-02-03

Abstract:

Background

Few therapeutic options are available for patients with moderate-to-severe hidradenitis suppurativa. We aimed to assess the efficacy of secukinumab in patients with moderate-to-severe hidradenitis suppurativa in two randomised trials.

Methods

SUNSHINE and SUNRISE were identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials done in 219 primary sites in 40 countries. Patients aged 18 years old or older with the capacity to provide written informed consent and with moderate-to-severe hidradenitis suppurativa (defined as a total of ≥5 inflammatory lesions affecting ≥2 distinct anatomical areas) for at least 1 year were eligible for inclusion. Included patients also agreed to daily use of topical over-the-counter antiseptics on the areas affected by hidradenitis suppurativa lesions while on study treatment. Patients were excluded if they had 20 or more fistulae at baseline, had ongoing active conditions requiring treatment with prohibited medication (eg, systemic biological immunomodulating treatment, live vaccines, or other investigational treatments), or met other exclusion criteria. In both trials, patients were randomly assigned (1:1:1) by means of interactive response technology to receive subcutaneous secukinumab 300 mg every 2 weeks, subcutaneous secukinumab 300 mg every 4 weeks, or subcutaneous placebo all via a 2 mL prefilled syringe in a double-dummy method as per treatment assignment. The primary endpoint was the proportion of patients with a hidradenitis suppurativa clinical response, defined as a decrease in abscess and inflammatory nodule count by 50% or more with no increase in the number of abscesses or in the number of draining fistulae compared with baseline, at week 16, assessed in the overall population. Hidradenitis suppurativa clinical response was calculated based on the number of abscesses, inflammatory nodules, draining fistulae, total fistulae, and other lesions in the hidradenitis suppurativa affected areas. Safety was assessed by evaluating the presence of adverse events and serious adverse events according to common terminology criteria for adverse events, which were coded using Medical Dictionary for Regulatory Activities terminology. Both the SUNSHINE, NCT03713619, and SUNRISE, NCT03713632, trials are registered with ClinicalTrials.gov.

Findings

Between Jan 31, 2019, and June 7, 2021, 676 patients were screened for inclusion in the SUNSHINE trial, of whom 541 (80%; 304 [56%] women and 237 [44%] men; mean age 36·1 years [SD 11·7]) were included in the analysis (181 [33%] in the secukinumab every 2 weeks group, 180 [33%] in the secukinumab every 4 weeks group, and 180 [33%] in the placebo group). Between the same recruitment dates, 687 patients were screened for inclusion in the SUNRISE trial, of whom 543 (79%; 306 [56%] women and 237 [44%] men; mean age 36·3 [11·4] years) were included in the analysis (180 [33%] in the secukinumab every 2 weeks group, 180 [33%] in the secukinumab every 4 weeks group, and 183 [34%] in the placebo group). In the SUNSHINE trial, significantly more patients in the secukinumab every 2 weeks group had a hidradenitis suppurativa clinical response (rounded average number of patients with response in 100 imputations, 81·5 [45%] of 181 patients) compared with the placebo group (60·7 [34%] of 180 patients; odds ratio 1·8 [95% CI 1·1–2·7]; p=0·0070). However, there was no significant difference between the number of patients in the secukinumab every 4 weeks group (75·2 [42%] of 180 patients) and the placebo group (1·5 [1·0–2·3]; p=0·042). Compared with the placebo group (57·1 [31%] of 183 patients), significantly more patients in the secukinumab every 2 weeks group (76·2 [42%] of 180 patients; 1·6 [1·1–2·6]; p=0·015) and the secukinumab every 4 weeks group (83·1 [46%] of 180 patients; 1·9 [1·2–3·0]; p=0·0022) had a hidradenitis suppurativa clinical response in the SUNRISE trial. Patient responses were sustained up to the end of the trials at week 52. The most common adverse event by preferred term up to week 16 was headache in both the SUNSHINE (17 [9%] patients in the secukinumab every 2 weeks group, 20 [11%] in the secukinumab every 4 weeks group, and 14 [8%] in the placebo group) and SUNRISE (21 [12%] patients in the secukinumab every 2 weeks group, 17 [9%] in the secukinumab every 4 weeks group, and 15 [8%] in the placebo group) trials. No study-related deaths were reported up to week 16. The safety profile of secukinumab in both trials was consistent with that previously reported, with no new or unexpected safety findings detected.

Interpretation

When given every 2 weeks, secukinumab was clinically effective at rapidly improving signs and symptoms of hidradenitis suppurativa with a favourable safety profile and with sustained response up to 52 weeks of treatment.

DOI: 10.1016/S0140-6736(23)00022-3

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00022-3/fulltext