Alexa B Kimball, Falk G Bechara, Aysha Badat, Evangelos J Giamarellos-Bourboulis, Alice B Gottlieb, Gregor B E Jemec, Ziad Reguiai, Axel P Villani, Ivette Alarcon, Amita Bansal, Francesca Gasperoni, Ruvie Martin, Bertrand Paguet, Lorenz Uhlmann, Hichem Zouater, Shoba Ravichandran, Afsaneh Alavi
{"title":"secukinumab治疗中重度化脓性汗腺炎的长期疗效和安全性：SUNSHINE和SUNRISE扩展试验的第104周结果","authors":"Alexa B Kimball, Falk G Bechara, Aysha Badat, Evangelos J Giamarellos-Bourboulis, Alice B Gottlieb, Gregor B E Jemec, Ziad Reguiai, Axel P Villani, Ivette Alarcon, Amita Bansal, Francesca Gasperoni, Ruvie Martin, Bertrand Paguet, Lorenz Uhlmann, Hichem Zouater, Shoba Ravichandran, Afsaneh Alavi","doi":"10.1093/bjd/ljae469","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>SUNSHINE and SUNRISE 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.</p><p><strong>Objectives: </strong>To evaluate the long-term efficacy, safety/tolerability, and maintenance of clinical response of secukinumab through Week 104 in the extension trial.</p><p><strong>Methods: </strong>Patients with a HS clinical response (HiSCR) at Week 52 of the core trials (extension trial baseline visit) entered a randomised withdrawal period. HiSCR responders receiving subcutaneous (s.c.) secukinumab 300 mg every 2/4 weeks (SECQ2W/SECQ4W) through Week 52 in the core trials were randomised 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.</p><p><strong>Results: </strong>Overall, 84.3% of patients completing 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=0.250) and 30% (SECQ4W-R-Q4W vs. SECQ4W-R-PBO; one-sided P=0.044). The median time to LOR was numerically longer in secukinumab arms versus placebo (SECQ2W-R-Q2W [283 days; 95% 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, 43.8% (SECQ2W-R-Q2W), 57.5% (SECQ2W-R-PBO), 39.7% (SECQ4W-R-Q4W) and 34.1% (SECQ4W-R-PBO) were achieving HiSCR at the time of LOR. Overall, the safety of secukinumab was consistent with the core trials.</p><p><strong>Conclusions: </strong>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 characterised safety profile in the core trials.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov ID NCT04179175.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0000,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Long-term efficacy and safety of secukinumab in patients with moderate-to-severe hidradenitis suppurativa: Week 104 results from the SUNSHINE and SUNRISE extension trial.\",\"authors\":\"Alexa B Kimball, Falk G Bechara, Aysha Badat, Evangelos J Giamarellos-Bourboulis, Alice B Gottlieb, Gregor B E Jemec, Ziad Reguiai, Axel P Villani, Ivette Alarcon, Amita Bansal, Francesca Gasperoni, Ruvie Martin, Bertrand Paguet, Lorenz Uhlmann, Hichem Zouater, Shoba Ravichandran, Afsaneh Alavi\",\"doi\":\"10.1093/bjd/ljae469\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>SUNSHINE and SUNRISE demonstrated sustained clinical efficacy of secukinumab in patients with moderate-to-severe hidradenitis suppurativa (HS) through 52 weeks. 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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.</p><p><strong>Results: </strong>Overall, 84.3% of patients completing 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=0.250) and 30% (SECQ4W-R-Q4W vs. SECQ4W-R-PBO; one-sided P=0.044). The median time to LOR was numerically longer in secukinumab arms versus placebo (SECQ2W-R-Q2W [283 days; 95% 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, 43.8% (SECQ2W-R-Q2W), 57.5% (SECQ2W-R-PBO), 39.7% (SECQ4W-R-Q4W) and 34.1% (SECQ4W-R-PBO) were achieving HiSCR at the time of LOR. Overall, the safety of secukinumab was consistent with the core trials.</p><p><strong>Conclusions: </strong>The primary endpoint of this trial was not met. HiSCR was maintained in many patients at the time of LOR. 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引用次数: 0
摘要
背景：SUNSHINE和SUNRISE在中重度化脓性汗腺炎（HS）患者中显示了52周的持续临床疗效。完成核心试验的患者可以进入为期4年的延长试验。目的：在扩展试验中评估secukinumab到104周的长期疗效、安全性/耐受性和临床反应的维持情况。方法：在核心试验（延伸试验基线访视）第52周出现HS临床反应（HiSCR）的患者进入随机停药期。在核心试验中，每2/4周接受皮下（s.c） secukinumab 300 mg （SECQ2W/SECQ4W）的HiSCR应答者在第52周被随机分为2:1，继续接受secukinumab （SECQ2W- r - q2w或SECQ4W- r - q4w）或安慰剂（SECQ2W- r - pbo或SECQ4W- r - pbo）至第104周。主要终点为反应丧失时间(LOR；在52周HiSCR应答者中（SECQ2W-R-Q2W vs SECQ2W-R-PBO和SECQ4W-R-Q4W vs SECQ4W-R-PBO）至104周。到第104周为止，每个比较到LOR的时间为1.25%（单侧）（单侧家庭α为2.5%）。如果达到LOR，患者可以继续接受开放标签secukinumab治疗。其他终点包括安全性和HiSCR。结果：总体而言，完成核心试验的患者中有84.3%进入了扩展试验；55.9%为52周HiSCR应答者。两种secukinumab给药方案均未达到主要终点。估计LOR风险降低13% (SECQ2W-R-Q2W vs SECQ2W-R-PBO；单侧P=0.250)和30% (SECQ4W-R-Q4W vs. SECQ4W-R-PBO；片面的P = 0.044)。与安慰剂组相比，secukinumab组到LOR的中位时间更长(SECQ2W-R-Q2W[283天；95% CI: 176, -] vs. SECQ2W-R-PBO[239天；95% ci: 120, -]；SECQ4W-R-Q4W[365天95% CI: 225， -] vs. SECQ4W-R-PBO[171天；95% ci: 113, 337])。在报告LOR的第52周HiSCR应答者中，43.8% （SECQ2W-R-Q2W）、57.5% （SECQ2W-R-PBO）、39.7% （SECQ4W-R-Q4W）和34.1% （SECQ4W-R-PBO）在LOR时达到HiSCR。总体而言，secukinumab的安全性与核心试验一致。结论：该试验的主要终点未达到。许多患者在LOR时仍维持HiSCR。secukinumab的安全性与先前在核心试验中描述的安全性一致。试验注册：Clinicaltrials.gov编号NCT04179175。
Long-term efficacy and safety of secukinumab in patients with moderate-to-severe hidradenitis suppurativa: Week 104 results from the SUNSHINE and SUNRISE extension trial.
Background: SUNSHINE and SUNRISE 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.
Objectives: To evaluate the long-term efficacy, safety/tolerability, and maintenance of clinical response of secukinumab through Week 104 in the extension trial.
Methods: Patients with a HS clinical response (HiSCR) at Week 52 of the core trials (extension trial baseline visit) entered a randomised withdrawal period. HiSCR responders receiving subcutaneous (s.c.) secukinumab 300 mg every 2/4 weeks (SECQ2W/SECQ4W) through Week 52 in the core trials were randomised 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.
Results: Overall, 84.3% of patients completing 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=0.250) and 30% (SECQ4W-R-Q4W vs. SECQ4W-R-PBO; one-sided P=0.044). The median time to LOR was numerically longer in secukinumab arms versus placebo (SECQ2W-R-Q2W [283 days; 95% 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, 43.8% (SECQ2W-R-Q2W), 57.5% (SECQ2W-R-PBO), 39.7% (SECQ4W-R-Q4W) and 34.1% (SECQ4W-R-PBO) were achieving HiSCR at the time of LOR. Overall, the safety of secukinumab was consistent with the core trials.
Conclusions: 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 characterised safety profile in the core trials.
Trial registration: Clinicaltrials.gov ID NCT04179175.
期刊介绍：
The British Journal of Dermatology (BJD) is committed to publishing the highest quality dermatological research. Through its publications, the journal seeks to advance the understanding, management, and treatment of skin diseases, ultimately aiming to improve patient outcomes.
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