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. 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, , and SUNRISE, , trials are registered with . 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. 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. Novartis Pharma.

中文翻译：

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苏金单抗治疗中重度化脓性汗腺炎（SUNSHINE 和 SUNRISE）：两项相同、多中心、随机、安慰剂对照、双盲 3 期试验的第 16 周和第 52 周结果


对于中度至重度化脓性汗腺炎患者，几乎没有可用的治疗选择。我们的目的是在两项随机试验中评估苏金单抗对中重度化脓性汗腺炎患者的疗效。 SUNSHINE 和 SUNRISE 是相同的、多中心、随机、安慰剂对照、双盲 3 期试验，在 40 个国家的 219 个主要地点进行。年满 18 岁或以上、有能力提供书面知情同意书且患有中度至重度化脓性汗腺炎（定义为总共≥5 个炎性病变，影响≥2 个不同解剖区域）至少 1 年的患者有资格纳入。纳入的患者还同意在接受研究治疗期间每天在受化脓性汗腺炎病变影响的区域使用外用非处方抗菌剂。如果患者在基线时有 20 个或更多瘘管，有持续的活动性疾病，需要使用禁用药物治疗（例如全身生物免疫调节治疗、活疫苗或其他研究治疗），或满足其他排除标准，则患者被排除。在这两项试验中，患者通过交互式反应技术被随机分配（1:1:1），接受每 2 周皮下注射 300 mg 苏金单抗、每 4 周皮下注射 300 mg 苏金单抗或皮下安慰剂，全部通过 2 mL 预装注射器注射。根据治疗分配采用双模拟方法。主要终点是具有化脓性汗腺炎临床反应的患者比例，定义为与基线相比，脓肿和炎性结节计数减少 50% 或更多，但脓肿数量或引流瘘管数量没有增加。第 16 周，对总体人群进行评估。 化脓性汗腺炎临床反应是根据化脓性汗腺炎受影响区域的脓肿、炎性结节、引流瘘管、总瘘管和其他病变的数量来计算的。通过根据不良事件的通用术语标准评估不良事件和严重不良事件的存在来评估安全性，这些术语标准使用监管活动术语医学词典进行编码。 SUNSHINE, 和 SUNRISE, 试验均已在 注册。 2019年1月31日至2021年6月7日期间，筛选了676名患者纳入SUNSHINE试验，其中541名（80%；304名[56%]名女性和237名[44%]名男性；平均年龄36·1岁[SD 11·7]）被纳入分析（苏金单抗每 2 周治疗组 181 [33%]，苏金单抗每 4 周治疗组 180 [33%]，安慰剂组 180 [33%]） 。在同一招募日期之间，筛选了 687 名患者纳入 SUNRISE 试验，其中 543 名患者（79%；306 [56%] 女性和 237 [44%] 男性；平均年龄 36·3 [11·4] 岁）纳入分析（苏金单抗每 2 周治疗组 180 例 [33%]，苏金单抗每 4 周治疗组 180 例 [33%]，安慰剂组 183 例 [34%]）。在 SUNSHINE 试验中，与安慰剂组相比，苏金单抗每 2 周治疗组中有更多患者出现化脓性汗腺炎临床缓解（100 次估算中出现缓解的患者平均数，181 名患者中有 81·5 [45%]）。 180 名患者中有 60·7 [34%]；比值比 1·8 [95% CI 1·1–2·7]；p=0·0070）。然而，每 4 周一次苏金单抗组（180 名患者中的 75·2 [42%]）和安慰剂组（1·5 [1·0–2·3]；p =0·042）。 与安慰剂组（183 名患者中的 57·1 [31%]）相比，苏金单抗每 2 周治疗组的患者明显更多（180 名患者中的 76·2 [42%]；1·6 [1·1–2· 6]；p=0·015）和每 4 周一次苏金单抗组（180 名患者中有 83·1 [46%]；1·9 [1·2–3·0]；p=0·0022）患有汗腺炎SUNRISE 试验中的化脓性临床反应。患者反应持续到第 52 周试验结束。截至第 16 周，最常见的不良事件是 SUNSHINE 组中的头痛（每 2 周苏金单抗组有 17 [9%] 名患者，20 [每 4 周苏金单抗组有 11%] 患者，安慰剂组有 14 名患者 [8%]）和 SUNRISE（每 2 周苏金单抗组有 21 名患者 [12%]，每 4 周苏金单抗组有 17 名患者 [9%]组，以及安慰剂组 15 项 [8%]）试验。截至第 16 周，没有报告与研究相关的死亡。两项试验中苏金单抗的安全性与之前报告的一致，没有发现新的或意外的安全性发现。每两周给药一次，苏金单抗在临床上可有效快速改善化脓性汗腺炎的体征和症状，具有良好的安全性，并且在治疗长达 52 周内具有持续反应。诺华制药。