Passera Anna, Muscianisi Elisa, Demanse David, Okoye Ginette A, Jemec Gregor B E, Mayo Tiffany, Hsiao Jennifer, Shi Vivian Y, Byrd Angel S, Wei Xiaoling, Uhlmann Lorenz, Vandemeulebroecke Marc, Ravichandran Shoba, Porter Martina L
Novartis Pharma AG, Basel, Switzerland.
Novartis Gene Therapies, Bannockburn, Illinois, USA.
J Eur Acad Dermatol Venereol. 2025 Aug;39(8):1410-1420. doi: 10.1111/jdv.20234. Epub 2024 Aug 5.
Defining hidradenitis suppurativa (HS) subtypes was previously limited by small sample sizes and poor interrater reliability; no study has investigated subtype treatment responses. The objective of this analysis was to characterize HS clusters in adult patients with moderate to severe HS and evaluate secukinumab treatment responses between clusters.
Clusters were identified via an unsupervised machine learning clustering analysis using baseline data from the randomized, placebo-controlled SUNSHINE (NCT03713619) and SUNRISE (NCT03713632) phase 3 trials. To assess treatment responses, patients received secukinumab every 2 (SECQ2W) or 4 weeks (SECQ4W) or placebo, for 16 weeks, after which, placebo patients randomly switched to SECQ2W/SECQ4W, and SECQ2W/SECQ4W patients maintained their original treatment, until week 52. Baseline outcomes included patient characteristics, disease characteristics and severity, HS-associated comorbidities and previous treatment exposures. Treatment response was assessed via the HS clinical response (HiSCR), abscess and inflammatory nodule (AN) count, flares and NRS30 (skin pain).
Based on baseline data, three clusters were identified from 1084 patients (Cluster 1: 54.1%, Cluster 2: 17.8%, Cluster 3: 28.1%). Cluster 1 was predominantly female (65.4%) and was characterized by milder HS. Cluster 2 had more patients from the Asia Pacific, Middle East and Africa region (58.5%) and was characterized by moderate HS. Cluster 3 had the highest rates of previous exposure to biologics (45.9%) and prior HS-related surgeries (47.5%) and was characterized by severe HS. SECQ2W and SECQ4W demonstrated efficacy versus placebo in all clusters at week 16; SECQ2W and SECQ4W efficacy was maintained to week 52. SECQ2W treatment showed a trend for greater efficacy versus SECQ4W in Cluster 3 through week 52.
Three HS clusters were identified. Secukinumab demonstrated benefit over placebo in all clusters. However, patients with more severe disease may take longer to respond and more frequent secukinumab dosing may be required for these patients.
SUNSHINE (NCT03713619) and SUNRISE (NCT03713632).
以往关于化脓性汗腺炎（HS）亚型的定义受样本量小和评分者间信度差的限制；尚无研究调查亚型的治疗反应。本分析的目的是对中度至重度HS成年患者的HS聚类进行特征描述，并评估各聚类之间司库奇尤单抗的治疗反应。
通过无监督机器学习聚类分析，利用随机、安慰剂对照的3期SUNSHINE（NCT03713619）和SUNRISE（NCT03713632）试验的基线数据确定聚类。为评估治疗反应，患者每2周（SECQ2W）或4周（SECQ4W）接受一次司库奇尤单抗或安慰剂治疗，共16周，之后，安慰剂组患者随机转为接受SECQ2W/SECQ4W治疗，SECQ2W/SECQ4W组患者维持原治疗，直至第52周。基线结局包括患者特征、疾病特征和严重程度、与HS相关的合并症以及既往治疗暴露情况。通过HS临床反应（HiSCR）、脓肿和炎性结节（AN）计数、病情发作和NRS30（皮肤疼痛）评估治疗反应。
根据基线数据，从1084例患者中识别出三个聚类（聚类1：54.1%，聚类2：17.8%，聚类3：28.1%）。聚类1以女性为主（65.4%），HS症状较轻。聚类2中来自亚太、中东和非洲地区的患者较多（58.5%），HS症状为中度。聚类3既往接受生物制剂治疗的比例最高（45.9%），既往进行HS相关手术的比例最高（47.5%），HS症状严重。在第16周时，SECQ2W和SECQ4W在所有聚类中均显示出优于安慰剂的疗效；SECQ2W和SECQ4W的疗效维持至第52周。直至第52周，在聚类3中，SECQ2W治疗显示出比SECQ4W疗效更佳的趋势。
识别出三个HS聚类。司库奇尤单抗在所有聚类中均显示出优于安慰剂的效果。然而，病情较重的患者可能需要更长时间才会有反应，这些患者可能需要更频繁地注射司库奇尤单抗。
SUNSHINE（NCT03713619）和SUNRISE（NCT03713632）。
