Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Dermatology and Department of Medicine, Division of Rheumatology and Immunology, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
Br J Dermatol. 2023 Jul 7;189(1):42-52. doi: 10.1093/bjd/ljad115.
Guselkumab has demonstrated favourable safety and efficacy across individual clinical studies in adults with moderate-to-severe plaque psoriasis.
To evaluate the safety of guselkumab in patients with psoriasis using pooled data from seven phase II/III studies (X-PLORE, VOYAGE 1, VOYAGE 2, NAVIGATE, ORION, ECLIPSE, Japan registration).
All studies, except NAVIGATE and ECLIPSE (active comparator-controlled only), included a 16-week placebo-controlled period; X-PLORE, VOYAGE 1 and VOYAGE 2 included both placebo and active controls. In most studies, guselkumab-treated patients received 100-mg subcutaneous injections at week 0, week 4, and then every 8 weeks thereafter. Safety data were summarized for the placebo-controlled period (weeks 0-16) and through the end of the reporting period (up to 5 years). Incidence rates of key safety events were integrated post hoc, adjusted for the duration of follow-up and reported per 100 patient-years (PY).
During the placebo-controlled period, 544 patients received placebo (165 PY) and 1220 received guselkumab (378 PY). Through the end of the reporting period, 2891 guselkumab-treated patients contributed 8662 PY of follow-up. During the placebo-controlled period, in the guselkumab and placebo groups, respectively, rates of adverse events (AEs) were 346/100 PY and 341/100 PY, and infections were 95.9/100 PY and 83.6/100 PY. Rates of serious AEs (6.3/100 PY vs. 6.7/100 PY), AEs leading to discontinuation (5.0/100 PY vs. 9.7/100 PY), serious infections (1.1/100 PY vs. 1.2/100 PY), malignancy (0.5 patients/100 PY vs. 0.0 patients/100 PY) and major adverse cardiovascular events (MACE; 0.3/100 PY vs. 0.0/100 PY) were low and comparable between guselkumab and placebo. Through the end of the reporting period, safety event rates were lower than or comparable to the placebo-controlled period in guselkumab-treated patients: AEs, 169/100 PY; infections, 65.9/100 PY; serious AEs, 5.3/100 PY; AEs leading to discontinuation, 1.6/100 PY; serious infections, 0.9/100 PY; malignancy, 0.7/100 PY; and MACE, 0.3/100 PY. There were no cases of Crohn disease, ulcerative colitis, opportunistic infection or active tuberculosis related to guselkumab.
In this comprehensive analysis of 2891 guselkumab-treated patients with psoriasis followed for up to 5 years (8662 PY), guselkumab demonstrated favourable safety, consistent with previous reports. Safety event rates in guselkumab-treated patients were similar to those observed with placebo and were consistent throughout long-term treatment.
古塞库单抗在多项针对中重度斑块状银屑病成人患者的单盲临床研究中表现出良好的安全性和疗效。
利用来自 7 项 2/3 期研究（X-PLORE、VOYAGE 1、VOYAGE 2、NAVIGATE、ORION、ECLIPSE、日本注册）的汇总数据评估古塞库单抗在银屑病患者中的安全性。
除 NAVIGATE 和 ECLIPSE 研究（仅活性对照）外，所有研究均包括 16 周安慰剂对照期；X-PLORE、VOYAGE 1 和 VOYAGE 2 同时包括安慰剂和活性对照。在大多数研究中，古塞库单抗治疗患者在第 0 周、第 4 周和此后每 8 周接受 100mg 皮下注射。在安慰剂对照期（第 0-16 周）和报告期末（最长 5 年）汇总安全性数据。对关键安全性事件的发生率进行了事后综合分析，根据随访时间进行了调整，并按每 100 患者年（PY）报告。
在安慰剂对照期，544 例患者接受安慰剂（165 PY），1220 例患者接受古塞库单抗（378 PY）。在报告期末，2891 例古塞库单抗治疗患者累计随访 8662 PY。在安慰剂对照期，古塞库单抗组和安慰剂组的不良事件（AE）发生率分别为 346/100 PY 和 341/100 PY，感染发生率分别为 95.9/100 PY 和 83.6/100 PY。严重不良事件（AE）发生率（6.3/100 PY 比 6.7/100 PY）、导致停药的 AE（5.0/100 PY 比 9.7/100 PY）、严重感染（1.1/100 PY 比 1.2/100 PY）、恶性肿瘤（0.5 例/100 PY 比 0.0 例/100 PY）和主要不良心血管事件（MACE；0.3/100 PY 比 0.0/100 PY）发生率较低，且古塞库单抗与安慰剂之间相当。在报告期末，古塞库单抗治疗患者的安全性事件发生率低于或与安慰剂对照期相当：AE，169/100 PY；感染，65.9/100 PY；严重 AE，5.3/100 PY；导致停药的 AE，1.6/100 PY；严重感染，0.9/100 PY；恶性肿瘤，0.7/100 PY；和 MACE，0.3/100 PY。古塞库单抗治疗患者中未发生与古塞库单抗相关的克罗恩病、溃疡性结肠炎、机会性感染或活动性结核。
在这项长达 5 年（8662 PY）的 2891 例接受古塞库单抗治疗的银屑病患者的综合分析中，古塞库单抗表现出良好的安全性，与之前的报告一致。古塞库单抗治疗患者的安全性事件发生率与安慰剂相似，并在长期治疗中保持一致。
