背景:本文旨在描述类风湿关节炎(RA)患者的恶性肿瘤,银屑病关节炎(PsA),强直性脊柱炎(AS),或接受upadacitinib(UPA)或主动比较剂治疗的非影像学轴性脊柱关节炎(nr-axSpA)。
方法:此综合安全性分析包括来自RA的11项3期UPA试验(6项试验)的数据,PsA(2次试验),AS(2个试验;一个2b/3阶段),和nr-axSpA(1次试验)。对RA的治疗引起的不良事件(TEAE)进行了总结(合并的UPA15mg[UPA15],合并的UPA30毫克[UPA30],阿达木单抗40毫克[ADA],甲氨蝶呤单一疗法[MTX]),PsA(合并UPA15,合并UPA30,ADA),AS(合并UPA15),和nr-axSpA(UPA15)。TEAE报告为暴露校正事件率(事件/100患者-年)。
结果:中位治疗时间为1.0-4.0年(RA最长6.6年)。在治疗和适应症中,不包括非黑素瘤皮肤癌(NMSC)的恶性率范围为0.2~1.1,而NMSC范围为0.0~1.4.在RA中,不包括NMSC的恶性肿瘤发生率在UPA15、UPA30、ADA、和MTX(乳腺癌和肺癌最常见)。在RA和PsA中,Kaplan-Meier分析显示,随着时间的推移,UPA15与UPA30在排除NMSC的恶性肿瘤事件发作中没有差异。在RA中,UPA30的NMSC率高于UPA15;UPA15和UPA30均高于ADA和MTX。在PsA,UPA15,UPA30和ADA中不包括NMSC和NMSC的恶性肿瘤发生率大致相似.在AS和nr-axSpA中,恶性肿瘤很少被报道.在整个临床项目中很少报道淋巴瘤事件。
结论:不包括NMSC的恶性肿瘤率在UPA15、UPA30、ADA、和MTX,并且在RA中一致,PsA,AS,还有nr-axSpA.在RA中,UPA观察到NMSC的剂量依赖性增加。
背景:ClinicaTrials.gov标识符:NCT02706873、NCT02675426、NCT02629159、NCT02706951、NCT02706847、NCT03086343、NCT03104400、NCT03104374、NCT03178487和NCT04169373。
BACKGROUND: This article aims to describe malignancies in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or non-radiographic axial spondyloarthritis (nr-axSpA) treated with upadacitinib (UPA) or active comparators.
METHODS: This integrated safety analysis includes data from 11 phase 3 UPA trials across RA (6 trials), PsA (2 trials), AS (2 trials; one phase 2b/3), and nr-axSpA (1 trial). Treatment-emergent adverse events (TEAEs) were summarized for RA (pooled UPA 15 mg [UPA15], pooled UPA 30 mg [UPA30], adalimumab 40 mg [ADA], methotrexate monotherapy [MTX]), PsA (pooled UPA15, pooled UPA30, ADA), AS (pooled UPA15), and nr-axSpA (UPA15). TEAEs were reported as exposure-adjusted event rates (events/100 patient-years).
RESULTS: Median treatment duration ranged from 1.0 to 4.0 years (with a maximum of 6.6 years in RA). Across treatments and indications, rates of malignancy excluding nonmelanoma skin cancer (NMSC) ranged from 0.2 to 1.1, while NMSC ranged from 0.0 to 1.4. In RA, rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX (breast and lung cancer were the most common). In RA and PsA, Kaplan-Meier analyses revealed no differences in event onset of malignancy excluding NMSC with UPA15 versus UPA30 over time. In RA, NMSC rates were higher with UPA30 than UPA15; both UPA15 and UPA30 were higher than ADA and MTX. In PsA, rates of malignancy excluding NMSC and NMSC were generally similar between UPA15, UPA30, and ADA. In AS and nr-axSpA, malignancies were reported infrequently. Few events of lymphoma were reported across the clinical programs.
CONCLUSIONS: Rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX and were consistent across RA, PsA, AS, and nr-axSpA. A dose-dependent increased rate of NMSC was observed with UPA in RA.
BACKGROUND: ClinicaTrials.gov identifier: NCT02706873, NCT02675426, NCT02629159, NCT02706951, NCT02706847, NCT03086343, NCT03104400, NCT03104374, NCT03178487, and NCT04169373.