Kimball Alexa B, Bechara Falk G, Badat Aysha, Giamarellos-Bourboulis Evangelos J, Gottlieb Alice B, Jemec Gregor B E, Reguiai Ziad, Villani Axel P, Alarcon Ivette, Bansal Amita, Gasperoni Francesca, Martin Ruvie, Paguet Bertrand, Uhlmann Lorenz, Zouater Hichem, Ravichandran Shoba, Alavi Afsaneh
Harvard Medical School and Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS), Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
International Centre for Hidradenitis Suppurativa/Acne Inversa (ICH), Department of Dermatology, Venereology and Allergology, Ruhr-University Bochum, Bochum, Germany.
Br J Dermatol. 2025 Mar 18;192(4):629-640. doi: 10.1093/bjd/ljae469.
The SUNSHINE and SUNRISE phase III trials demonstrated sustained clinical efficacy of secukinumab in patients with moderate-to-severe hidradenitis suppurativa (HS) through 52 weeks. Patients completing the core trials could enter a 4-year extension trial.
To evaluate the long-term efficacy, safety/tolerability and maintenance of clinical response to secukinumab through week 104 in the extension trial.
Patients with a hidradenitis suppurativa (HS) clinical response (HiSCR) at week 52 of the core trials (extension trial baseline visit) entered a randomized withdrawal period. HiSCR responders receiving subcutaneous secukinumab 300 mg every 2 or 4 weeks (SECQ2W/SECQ4W) through week 52 in the core trials were randomized 2 : 1 to continue secukinumab (SECQ2W-R-Q2W or SECQ4W-R-Q4W) or receive placebo (SECQ2W-R-PBO or SECQ4W-R-PBO) through week 104. The primary endpoint was time to loss of response (LOR; newly defined for this trial) through week 104 in week 52 HiSCR responders (SECQ2W-R-Q2W vs. SECQ2W-R-PBO and SECQ4W-R-Q4W vs. SECQ4W-R-PBO). Time to LOR was tested at 1.25% (one-sided) for each comparison (one-sided familywise alpha of 2.5%) through week 104. If LOR was met, patients could remain in the trial on open-label secukinumab treatment. Additional endpoints included safety and HiSCR. The trial was registered with ClinicalTrials.gov (NCT04179175).
Overall, 84.3% of patients who completed the core trials entered the extension trial; 55.9% were week 52 HiSCR responders. The primary endpoint was not met for either secukinumab dosing regimen. The estimated risk reduction for LOR was 13% (SECQ2W-R-Q2W vs. SECQ2W-R-PBO; one-sided P = 0.25) and 30% (SECQ4W-R-Q4W vs. SECQ4W-R-PBO; one-sided P = 0.04). The median time to LOR was numerically longer in the secukinumab arms vs. placebo {SECQ2W-R-Q2W [283 days; 95% confidence interval (CI) 176, -] vs. SECQ2W-R-PBO [239 days; 95% CI 120, -]; SECQ4W-R-Q4W [365 days 95% CI 225, -] vs. SECQ4W-R-PBO [171 days; 95% CI 113-337]}. In week 52 HiSCR responders reporting LOR, 44% (SECQ2W-R-Q2W), 58% (SECQ2W-R-PBO), 40% (SECQ4W-R-Q4W) and 34% (SECQ4W-R-PBO) were achieving HiSCR at the time of LOR. Overall, the safety of secukinumab was consistent with the core trials.
The primary endpoint of this trial was not met. HiSCR was maintained in many patients at the time of LOR. The safety of secukinumab was consistent with the previously characterized safety profile in the core trials.
SUNSHINE和SUNRISE III期试验证明，司库奇尤单抗在中度至重度化脓性汗腺炎（HS）患者中具有持续52周的临床疗效。完成核心试验的患者可进入为期4年的扩展试验。
在扩展试验中评估司库奇尤单抗至第104周的长期疗效、安全性/耐受性及临床反应的维持情况。
核心试验第52周（扩展试验基线访视）时有化脓性汗腺炎（HS）临床反应（HiSCR）的患者进入随机撤药期。在核心试验中至第52周接受皮下注射司库奇尤单抗300mg每2周或4周一次（SECQ2W/SECQ4W）的HiSCR反应者按2:1随机分组，至第104周继续使用司库奇尤单抗（SECQ2W-R-Q2W或SECQ4W-R-Q4W）或接受安慰剂（SECQ2W-R-PBO或SECQ4W-R-PBO）。主要终点是第52周HiSCR反应者（SECQ2W-R-Q2W与SECQ2W-R-PBO以及SECQ4W-R-Q4W与SECQ4W-R-PBO）至第104周失去反应（LOR；为本试验新定义）的时间。每次比较时在第104周对LOR时间进行1.25%（单侧）检验（单侧家族性α为2.5%）。如果达到LOR，患者可继续接受开放标签的司库奇尤单抗治疗留在试验中。其他终点包括安全性和HiSCR。该试验已在ClinicalTrials.gov注册（NCT04179175）。
总体而言，84.3%完成核心试验的患者进入了扩展试验；55.9%为第52周HiSCR反应者。两种司库奇尤单抗给药方案均未达到主要终点。LOR的估计风险降低分别为13%（SECQ2W-R-Q2W与SECQ2W-R-PBO；单侧P=0.25）和30%（SECQ4W-R-Q4W与SECQ4W-R-PBO；单侧P=0.04）。与安慰剂相比，司库奇尤单抗组LOR的中位时间在数值上更长{SECQ2W-R-Q2W[283天；95%置信区间（CI）176，-]与SECQ2W-R-PBO[239天；95%CI 120，-]；SECQ4W-R-Q4W[365天95%CI 225，-]与SECQ4W-R-PBO[171天；95%CI 113 - 337]}。在报告LOR的第52周HiSCR反应者中，44%（SECQ2W-R-Q2W）、58%（SECQ2W-R-PBO）、40%（SECQ4W-R-Q4W）和34%（SECQ4W-R-PBO）在LOR时达到HiSCR。总体而言，司库奇尤单抗的安全性与核心试验一致。
本试验未达到主要终点。许多患者在LOR时维持了HiSCR。司库奇尤单抗的安全性与核心试验中先前描述的安全性特征一致。
