通过 2 项 Guselkumab 治疗银屑病关节炎的 III 期临床试验 1 年的汇总安全性结果。
Pooled Safety Results Through 1 Year of 2 Phase III Trials of Guselkumab in Patients With Psoriatic Arthritis.
机构信息
P. Rahman, MD, Memorial University of Newfoundland, St. John's, Newfoundland, Canada;
C.T. Ritchlin, MD, MPH, University of Rochester, Rochester, New York, USA.
出版信息
J Rheumatol. 2021 Dec;48(12):1815-1823. doi: 10.3899/jrheum.201532. Epub 2021 May 1.
OBJECTIVE
Evaluate the safety of guselkumab (monoclonal antibody targeting interleukin [IL]-23p19) in patients with psoriatic arthritis (PsA) through 1 year (1Y) of the phase III DISCOVER-1 and DISCOVER-2 trials.
METHODS
Patients with active PsA (n = 1120; biologic-naïve except 118 patients treated with tumor necrosis factor inhibitors in DISCOVER-1) were randomized to subcutaneous guselkumab 100 mg every 4 weeks (Q4W) or at Week 0, Week 4, then every 8 weeks (Q8W); or placebo. At Week 24, patients in the placebo group switched to guselkumab 100 mg Q4W. Treatment continued through 1Y and 2 years for DISCOVER-1 and DISCOVER-2, respectively. In this pooled analysis, patients with ≥ 1 adverse event (AE) through 1Y were standardized for 100 patient-years [100 PYs] of follow-up.
RESULTS
Through Week 24, adverse events (AEs) were consistent between patients treated with placebo and guselkumab (Q4W + Q8W). AEs were 142.8/100 PYs and 150.6/100 PYs, serious AEs were 7.1/100 PYs and 4.4/100 PYs, and AEs leading to study agent discontinuation were 4.1/100 PYs and 3.8/100 PYs, respectively. Through 1Y in patients treated with guselkumab, no uveitis, active tuberculosis, opportunistic infections, or inflammatory bowel disease were observed, and low rates of malignancy and major adverse cardiovascular (CV) events were observed. Injection-site reactions occurred in 1.7%, and antibodies to guselkumab in 4.5% of patients treated with guselkumab through 1Y; the vast majority of antibodies to guselkumab were nonneutralizing. Serum hepatic transaminase elevations (more common with Q4W than Q8W dosing) and decreased neutrophil counts were generally mild, transient, and did not require treatment discontinuation, with minimal change from Week 24 to 1Y.
CONCLUSION
Guselkumab 100 mg Q4W and Q8W were well tolerated in patients with PsA, with no new safety concerns through 1Y of the phase III DISCOVER trials. Guselkumab safety through 1Y in patients with PsA is consistent with that established in patients with psoriasis who were treated with guselkumab. [ClinicalTrials.gov: NCT03162796 and NCT03158285].
目的
通过 III 期 DISCOVER-1 和 DISCOVER-2 试验的 1 年（1Y）评估 Guselkumab（靶向白细胞介素[IL]-23p19 的单克隆抗体）在患有银屑病关节炎（PsA）患者中的安全性。
方法
1120 例活动性 PsA 患者（生物制剂初治，除 118 例在 DISCOVER-1 中接受肿瘤坏死因子抑制剂治疗的患者外）被随机分配至 Guselkumab 100mg 每 4 周（Q4W）或在第 0、4 周和第 8 周（Q8W）；或安慰剂。在第 24 周，安慰剂组的患者转为 Guselkumab 100mg Q4W。对于 DISCOVER-1 和 DISCOVER-2，治疗分别持续至 1Y 和 2Y。在这项汇总分析中，通过 1Y 标准化了有≥1 个不良事件（AE）的患者，随访时间为 100 患者年[100 PYs]。
结果
在第 24 周，安慰剂和 Guselkumab（Q4W+Q8W）治疗的患者的不良事件（AE）一致。AE 分别为 142.8/100 PYs 和 150.6/100 PYs，严重 AE 分别为 7.1/100 PYs 和 4.4/100 PYs，AE 导致研究药物停药分别为 4.1/100 PYs 和 3.8/100 PYs。在接受 Guselkumab 治疗的患者中，通过 1Y 未观察到葡萄膜炎、活动性结核病、机会性感染或炎症性肠病，且恶性肿瘤和主要不良心血管（CV）事件的发生率较低。1Y 时，注射部位反应发生率为 1.7%，Guselkumab 抗体发生率为 4.5%；绝大多数 Guselkumab 抗体是非中和性的。血清肝转氨酶升高（与 Q4W 比 Q8W 剂量更常见）和中性粒细胞计数减少通常为轻度、短暂，无需停药，与第 24 周相比，到第 1Y 时变化最小。
结论
在患有 PsA 的患者中，Guselkumab 100mg Q4W 和 Q8W 耐受良好，在 III 期 DISCOVER 试验的 1Y 期间没有新的安全性问题。在接受 Guselkumab 治疗的 PsA 患者中，1Y 时的安全性与在接受 Guselkumab 治疗的银屑病患者中确立的安全性一致。[临床试验.gov：NCT03162796 和 NCT03158285]。
Zotero 插件