乌帕替尼治疗银屑病关节炎、强直性脊柱炎和非放射学中轴型脊柱关节炎长达5年的安全性概况：临床试验综合分析

Safety Profile of Upadacitinib up to 5 Years in Psoriatic Arthritis, Ankylosing Spondylitis, and Non-radiographic Axial Spondyloarthritis: An Integrated Analysis of Clinical Trials.

作者信息

Burmester Gerd R, Stigler Jayne, Rubbert-Roth Andrea, Tanaka Yoshiya, Azevedo Valderilio F, Coombs Derek, Lagunes Ivan, Lippe Ralph, Wung Peter, Gensler Lianne S

机构信息

Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.

AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA.

出版信息

Rheumatol Ther. 2024 Jun;11(3):737-753. doi: 10.1007/s40744-024-00671-4. Epub 2024 Apr 29.

DOI:10.1007/s40744-024-00671-4

PMID:38683479

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11111431/

Abstract

INTRODUCTION

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.

CONCLUSION

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.

TRIAL REGISTRATION

SELECT-AXIS 1: NCT03178487; SELECT-AXIS 2: NCT04169373; SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374.

摘要

引言

这项针对2/3期和3期SELECT试验的综合分析描述了口服Janus激酶抑制剂乌帕替尼在银屑病关节炎（PsA）、强直性脊柱炎（AS）和非放射学中轴型脊柱关节炎（nr-axSpA）（包括合并的中轴型脊柱关节炎[axSpA]）长达5年暴露期的安全性概况。

方法

分析了乌帕替尼在PsA（2项试验）、AS（2项试验）和nr-axSpA（1项试验）的5项试验的安全性数据，数据截止日期为2022年8月15日。一项PsA研究纳入阿达木单抗作为活性对照药。汇总了PsA（乌帕替尼15mg每日一次与阿达木单抗40mg每两周一次）、AS（乌帕替尼15mg）、nr-axSpA（乌帕替尼15mg）和合并的axSpA（axSpA试验中汇总的乌帕替尼15mg）的治疗中出现的不良事件（TEAE）。TEAE报告为每100患者年的暴露调整事件率（E/100 PY）。

结果

共有1789例患者（PsA，n = 907；AS，n = 596；nr-axSpA，n = 286）接受≥1剂乌帕替尼15mg，暴露时间为3689患者年，或接受阿达木单抗（n = 429），暴露时间为1147患者年。总体TEAE和严重TEAE在PsA中最高，且乌帕替尼的数值高于阿达木单抗；AS和nr-axSpA之间的发生率相似。在PsA中，与阿达木单抗相比，乌帕替尼观察到严重感染、带状疱疹（HZ）、淋巴细胞减少和非黑色素瘤皮肤癌（NMSC）的发生率更高。在PsA中，乌帕替尼和阿达木单抗之间排除NMSC的恶性肿瘤发生率、判定的主要不良心血管事件和判定的静脉血栓栓塞事件发生率相当，且在各疾病中相似。