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

IF 2.9 3区医学 Q2 RHEUMATOLOGY

Rheumatology and Therapy Pub Date : 2024-04-29 DOI:10.1007/s40744-024-00671-4

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

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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.

Abstract Image

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乌达帕替尼治疗银屑病关节炎、强直性脊柱炎和非放射性轴性脊柱关节炎长达 5 年的安全性概况：临床试验综合分析

引言本研究对2/3期和3期SELECT试验进行了综合分析，描述了口服Janus激酶抑制剂乌达帕替尼在银屑病关节炎（PsA）、强直性脊柱炎（AS）和非放射性轴性脊柱关节炎（nr-axSpA）（包括汇总的轴性脊柱关节炎[axSpA]）中暴露长达5年的安全性概况。方法分析了截至2022年8月15日数据截止时，达帕替尼治疗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。其中一项PsA研究将阿达木单抗作为活性比较药。总结了PsA（汇集达帕替尼15毫克，每日一次和阿达木单抗40毫克，每两周一次）、AS（汇集达帕替尼15毫克）、nr-axSpA（达帕替尼15毫克）和汇集axSpA（汇集axSpA试验中的达帕替尼15毫克）的治疗突发不良事件（TEAEs）。结果共有1789名患者（PsA，n = 907；AS，n = 596；nr-axSpA，n = 286）在3689年的暴露期中接受了≥1个剂量的upadacitinib 15 mg，或在1147年的暴露期中接受了阿达木单抗（n = 429）。总体TEAEs和严重TEAEs在PsA中最高，且达达替尼比阿达木单抗高；AS和nr-axSpA的发生率相似。在PsA中，达帕替尼与阿达木单抗相比，可观察到更高的严重感染、带状疱疹（HZ）、淋巴细胞减少症和非黑色素瘤皮肤癌（NMSC）发生率。结论在PsA中，达帕替尼与阿达木单抗相比，可观察到更高的严重感染、HZ、淋巴细胞减少症和NMSC发生率；在PsA中，达帕替尼与axSpA相比，大多数TEAEs的发生率略有升高。达帕替尼15毫克在不同疾病状态下的安全性基本一致，未发现新的安全性信号。试验注册SELECT-AXIS 1: NCT03178487; SELECT-AXIS 2: NCT04169373; SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374。

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来源期刊

Rheumatology and Therapy RHEUMATOLOGY-

CiteScore

6.00

自引率

5.30%

发文量

审稿时长

6 weeks

期刊介绍： Aims and Scope Rheumatology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of rheumatologic therapies. Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed. Areas of focus include, but are not limited to, rheumatoid arthritis, gout, gouty arthritis, psoriatic arthritis, osteoarthritis, juvenile idiopathic/rheumatoid arthritis, systemic lupus erythematosus, axial spondyloarthritis, Pompe’s disease, inflammatory joint conditions, musculoskeletal conditions, systemic sclerosis, and fibromyalgia. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial protocols, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Rheumatology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research. Ethics and Disclosures The journal is a member of the Committee on Publication Ethics (COPE) and subscribes to its principles on how to deal with acts of misconduct thereby committing to investigate allegations of misconduct in order to ensure the integrity of research. Content in this journal is peer-reviewed (Single-blind). 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