Dermatologikum Berlin and SCIderm Research Institute, Hamburg, Germany.
K Papp Clinical Research and Probity Research, Inc., Waterloo, Canada.
Br J Dermatol. 2019 May;180(5):1039-1049. doi: 10.1111/bjd.17454.
BACKGROUND: Long-term evaluation is required to confirm the safety profile of newer biologic agents. OBJECTIVES: To report on pooled safety data from the ongoing VOYAGE 1 (NCT02207231) and VOYAGE 2 (NCT02207244) trials through 100 weeks of follow-up. METHODS: Patients were randomized to either guselkumab 100 mg at weeks 0 and 4 and every 8 weeks thereafter; placebo at weeks 0, 4, 12 followed by guselkumab 100 mg at weeks 16 and 20 and every 8 weeks thereafter; or adalimumab 80 mg at week 0, 40 mg at week 1, and 40 mg every 2 weeks thereafter. Patients who received adalimumab crossed over to guselkumab at week 52 (VOYAGE 1) and at/after week 28 based on clinical response (VOYAGE 2). Open-label extensions, in which all patients received guselkumab, started at week 52 (VOYAGE 1) and week 76 (VOYAGE 2). Rates of adverse events (AEs) per 100 patient-years (PYs) are presented through 100 weeks of follow-up. RESULTS: Through week 52, observed rates for guselkumab- and adalimumab-treated patients, respectively, were 262·45 per 100 PYs and 328·28 per 100 PYs for AEs, 6·20 per 100 PYs and 7·77 per 100 PYs for serious AEs (SAEs), 1·22 per 100 PYs and 1·79 per 100 PYs for serious infections (SIs), 0·28 per 100 PYs and 0·40 per 100 PYs for malignancies other than nonmelanoma skin cancers (NMSCs), 0·56 per 100 PYs and 0·40 per 100 PYs for NMSCs, and 0·47 per 100 PYs and 0·40 per 100 PYs for major adverse cardiovascular events (MACEs). Rates among patients treated with guselkumab through week 52 and week 100, respectively, were 262·45 per 100 PYs and 210·41 per 100 PYs for AEs, 6·20 and 6·29 per 100 PYs, for SAEs, 1·22 per 100 PYs and 1·06 per 100 PYs for SIs, 0·28 per 100 PYs and 0·38 per 100 PYs for malignancies, 0·56 per 100 PYs and 0·39 per 100 PYs for NMSCs, and 0·47 per 100 PYs and 0·38 per 100 PYs for MACEs. Among patients treated with adalimumab, rates of AEs, SAEs, SIs, malignancies, NMSCs, and MACEs showed some variability before and after crossover to guselkumab, although no new safety signals were noted after crossover. CONCLUSIONS: The safety profile for guselkumab remains favourable through 100 weeks of treatment in patients with moderate-to-severe psoriasis.
背景：需要长期评估才能确认新型生物制剂的安全性概况。
目的：报告正在进行的 VOYAGE 1（NCT02207231）和 VOYAGE 2（NCT02207244）试验中直至 100 周随访的汇总安全性数据。
方法：患者被随机分配至 Guselkumab 100mg 组，分别在第 0 周和第 4 周以及此后每 8 周给药一次；安慰剂组在第 0 周、第 4 周和第 12 周，随后在第 16 周和第 20 周给予 Guselkumab 100mg 并此后每 8 周给药一次；或阿达木单抗 80mg 第 0 周、40mg 第 1 周和此后每 2 周 40mg。接受阿达木单抗的患者在第 52 周（VOYAGE 1）和基于临床反应的第 28 周（VOYAGE 2）交叉至 Guselkumab。所有患者在第 52 周（VOYAGE 1）和第 76 周（VOYAGE 2）开始进行开放标签扩展。通过 100 周随访，每 100 患者年（PYs）的不良事件（AEs）发生率报告。
结果：在第 52 周之前，分别接受 Guselkumab 和阿达木单抗治疗的患者的 AE 发生率为每 100 PYs 262.45 例和 328.28 例，SAE 发生率为每 100 PYs 6.20 例和 7.77 例，严重感染（SI）发生率为每 100 PYs 1.22 例和 1.79 例，非黑色素瘤皮肤癌（NMSC）以外的恶性肿瘤发生率为每 100 PYs 0.28 例和 0.40 例，NMSC 发生率为每 100 PYs 0.56 例和 0.40 例，重大不良心血管事件（MACE）发生率为每 100 PYs 0.47 例和 0.40 例。在第 52 周和第 100 周接受 Guselkumab 治疗的患者中，AE 的发生率分别为每 100 PYs 262.45 例和 210.41 例，SAE 发生率分别为每 100 PYs 6.20 例和 6.29 例，SI 发生率分别为每 100 PYs 1.22 例和 1.06 例，恶性肿瘤发生率分别为每 100 PYs 0.28 例和 0.38 例，NMSC 发生率分别为每 100 PYs 0.56 例和 0.39 例，MACE 发生率分别为每 100 PYs 0.47 例和 0.38 例。在交叉至 Guselkumab 之前和之后，接受阿达木单抗治疗的患者的 AE、SAE、SI、恶性肿瘤、NMSC 和 MACE 发生率存在一定变化，但在交叉后未出现新的安全性信号。
结论：在中重度银屑病患者中，Guselkumab 治疗 100 周的安全性状况仍然良好。
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