背景:对2/3期和3期SELECT试验的综合分析描述了upadacitinib的安全性,口服Janus激酶抑制剂,长达5年的银屑病关节炎(PsA)暴露,强直性脊柱炎(AS),和非影像学轴性脊柱关节炎(nr-axSpA)(包括合并的轴性脊柱关节炎[axSpA])。
方法:来自五项upadacitinib在PsA中的试验(2项试验)的安全性数据,AS(2次试验),和nr-axSpA(1项试验)进行了分析,直至2022年8月15日的数据截止日期。一项PsA研究包括阿达木单抗作为活性比较物。总结了PsA(合并upadacitinib15mg每日一次和阿达木单抗40mg每两周一次)的治疗引起的不良事件(TEAE),AS(合并upadacitinib15mg),nr-axSpA(upadacitinib15mg),和合并axSpA(合并uppadacitinib15mg,来自axSpA试验)。TEAE报告为每100例患者年暴露校正事件率(E/100PY)。
结果:总共1789例患者(PsA,n=907;AS,n=596;nr-axSpA,n=286)接受≥1剂量的upadacitinib15mg用于3689PY暴露或阿达木单抗(n=429)用于1147PY暴露。总体TEAE和严重TEAE在PsA中最高,与阿达木单抗相比,upadacitinib的数值更高;AS和nr-axSpA的发生率相似。在PsA,严重感染率较高,带状疱疹(HZ),淋巴细胞减少,和非黑色素瘤皮肤癌(NMSC)观察到upadacitinib与阿达木单抗.不包括NMSC的恶性肿瘤率,裁定的主要不良心血管事件,和裁定的静脉血栓栓塞事件在PsA中在upadacitinib和阿达木单抗之间具有可比性,并且在不同疾病中相似.
结论:严重感染率较高,HZ,淋巴细胞减少,和NMSC在PsA中观察到upadacitinib与阿达木单抗的比较;在PsA中观察到upadacitinib与axSpA中观察到大多数这些TEAE的发生率略有升高.Upadacitinib15mg在所有疾病状态下显示出基本一致的安全性,没有发现新的安全性信号。
背景:选择轴1:NCT03178487;选择轴2:NCT04169373;选择轴1:NCT03104400;选择轴2:NCT03104374。
银屑病关节炎,强直性脊柱炎,和非影像学轴性脊柱关节炎是一组引起关节和/或脊柱疼痛和炎症的疾病。安全性数据来自五项研究:两项在银屑病关节炎中,两个在强直性脊柱炎中,和一个非影像学轴性脊柱关节炎。患者接受upadacitinib或阿达木单抗治疗长达5年。阿达木单抗仅用于参与两项银屑病关节炎研究之一的患者。与强直性脊柱炎和非影像学轴性脊柱关节炎患者相比,银屑病关节炎患者的治疗副作用更为常见;与阿达木单抗相比,银屑病关节炎患者使用upadacitinib的副作用更多。不同治疗组和疾病的患者数量相似,副作用使他们停止治疗。癌症病例的数量(除了上层皮肤的癌症),心血管问题,在银屑病关节炎和不同疾病中,upadacitinib组和阿达木单抗组的血凝块相似.严重感染,引起水泡的疼痛性皮疹(带状疱疹,也通常称为带状疱疹),低水平的白细胞,与阿达木单抗相比,在银屑病关节炎患者中,upadacitinib更常见于皮肤上层的癌症;总体而言,与强直性脊柱炎和非影像学轴性脊柱关节炎患者相比,银屑病关节炎患者使用upadacitinib发生这些事件的频率更高.我们的结果表明,upadacitinib的安全性在不同疾病中大致相似,患者可以很好地耐受长达5年。upadacitinib治疗未发现新的安全风险。
BACKGROUND: This integrated analysis of the phase 2/3 and phase 3 SELECT trials describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, for up to 5 years of exposure across psoriatic arthritis (PsA), ankylosing spondylitis (AS), and non-radiographic axial spondyloarthritis (nr-axSpA) (including pooled axial spondyloarthritis [axSpA]).
METHODS: Safety data from five trials of upadacitinib in PsA (2 trials), AS (2 trials), and nr-axSpA (1 trial) were analyzed up to a data cut-off of August 15, 2022. One PsA study included adalimumab as an active comparator. Treatment-emergent adverse events (TEAEs) were summarized for PsA (pooled upadacitinib 15 mg once daily and adalimumab 40 mg biweekly), AS (pooled upadacitinib 15 mg), nr-axSpA (upadacitinib 15 mg), and pooled axSpA (pooled upadacitinib 15 mg from axSpA trials). TEAEs were reported as exposure-adjusted event rates per 100 patient-years (E/100 PY).
RESULTS: A total of 1789 patients (PsA, n = 907; AS, n = 596; nr-axSpA, n = 286) received ≥ 1 dose of upadacitinib 15 mg for 3689 PY of exposure or adalimumab (n = 429) for 1147 PY of exposure. Overall TEAEs and serious TEAEs were highest in PsA and numerically higher with upadacitinib versus adalimumab; rates were similar between AS and nr-axSpA. In PsA, higher rates of serious infection, herpes zoster (HZ), lymphopenia, and nonmelanoma skin cancer (NMSC) were observed with upadacitinib versus adalimumab. Rates of malignancy excluding NMSC, adjudicated major adverse cardiovascular events, and adjudicated venous thromboembolic events were comparable between upadacitinib and adalimumab in PsA and were similar across diseases.
CONCLUSIONS: Higher rates of serious infection, HZ, lymphopenia, and NMSC were observed with upadacitinib versus adalimumab in PsA; slightly elevated rates for most of these TEAEs were seen with upadacitinib in PsA versus axSpA. Upadacitinib 15 mg demonstrated a generally consistent safety profile across disease states with no new safety signals identified.
BACKGROUND: SELECT-AXIS 1: NCT03178487; SELECT-AXIS 2: NCT04169373; SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374.
Psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis are a group of diseases that cause pain and inflammation of the joints and/or spine. Safety data were combined from five studies: two in psoriatic arthritis, two in ankylosing spondylitis, and one in non-radiographic axial spondyloarthritis. Patients were treated with upadacitinib or adalimumab for up to 5 years. Adalimumab was only used for patients participating in one of the two psoriatic arthritis studies. Side effects from treatment were more common in patients with psoriatic arthritis than those with ankylosing spondylitis and non-radiographic axial spondyloarthritis; more patients with psoriatic arthritis had side effects with upadacitinib than adalimumab. A similar number of patients across treatment groups and diseases had side effects that made them stop treatment. The number of cancer cases (except cancer of the upper layer of the skin), cardiovascular issues, and blood clots were similar between the upadacitinib and adalimumab groups in psoriatic arthritis and across diseases. Serious infections, painful rashes that cause blisters (herpes zoster, also commonly referred to as shingles), low levels of white blood cells, and cancer of the upper layer of the skin were more common with upadacitinib than adalimumab in patients with psoriatic arthritis; overall, these events occurred more often with upadacitinib in patients with psoriatic arthritis than with ankylosing spondylitis and non-radiographic axial spondyloarthritis. Our results showed that the safety of upadacitinib was generally similar across diseases, and patients could tolerate it well for up to 5 years. No new safety risks were found with upadacitinib treatment.