Safety Profile of Upadacitinib: Descriptive Analysis in Over 27,000 Patient-Years Across Rheumatoid Arthritis, Psoriatic Arthritis, Axial Spondyloarthritis, Atopic Dermatitis, and Inflammatory Bowel Disease

IF 4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Therapy Pub Date : 2025-08-28 DOI:10.1007/s12325-025-03328-y

Gerd R. Burmester, Atul Deodhar, Alan D. Irvine, Remo Panaccione, Kevin L. Winthrop, Ruth Ann Vleugels, Gweneth Levy, Smitha Suravaram, Hannah Palac, Lani Wegrzyn, Sharanya Ford, Sebastian Meerwein, Emma Guttman-Yassky

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引用次数: 0

Abstract

Introduction

We report the long-term safety of upadacitinib (oral, selective, and reversible Janus kinase inhibitor) in rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-axSpA), atopic dermatitis (AD), Crohn’s disease (CD), and ulcerative colitis (UC).

Methods

Data were analyzed from 16 studies (data cutoff August 15, 2024). Each treatment group was pooled across studies within each indication. Active comparator arms included adalimumab (RA/PsA) and methotrexate (RA). Treatment-emergent adverse events (TEAEs) were reported as exposure-adjusted incidence rates per 100 patient-years (n/100 PY).

Results

This analysis included 8632 (RA, n = 3209; PsA, n = 907; AS, n = 596; nr-axSpA, n = 286; AD, n = 2683; CD, n = 450; UC, n = 501) upadacitinib-treated patients over 27,164.2 patient-years (range 199.4–12,315.8 PY across indications). Rates (n/100 PY) of any TEAEs ranged from 112.0 (AS) to 401.1 (RA). Most frequently reported TEAEs included COVID-19, upper respiratory tract infection, nasopharyngitis, herpes zoster, urinary tract infection, and acne (primarily patients with AD). Serious TEAEs ranged from 4.5 (AD) to 11.0 (UC), and those leading to discontinuation ranged from 2.9 (AS) to 8.3 (UC). TEAEs leading to death ranged from 0 (nr-axSpA, UC) to 0.7 (RA). Among upadacitinib-treated patients across indications, rates of adverse events of special interest ranged from 1.3 to 4.6 (serious infection), 2.4–6.6 (herpes zoster), 0.2–0.9 (malignancy excluding nonmelanoma skin cancer [NMSC]), 0–1.4 (NMSC), 0–0.5 (major adverse cardiovascular event [MACE]), 0–0.9 (venous thromboembolism [VTE]), and 0–9.2 (elevated creatine kinase). In RA and PsA, herpes zoster, NMSC, and elevated creatine kinase rates were numerically higher with upadacitinib vs active comparators. Serious infection, herpes zoster, malignancy (excluding NMSC), NMSC, MACE, and VTE rates remained stable over time.

Conclusion

This descriptive analysis indicates a long-term safety profile of upadacitinib consistent with previous reports, further supporting long-term treatment of chronic diseases with upadacitinib. Variations in TEAE rates across indications likely reflected differences in populations and underlying comorbidities.

Trial Registration

ClinicalTrials.gov identifiers NCT02675426, NCT02706951, NCT02706847, NCT02629159, NCT02706873, NCT03086343, NCT03104374, NCT03104400, NCT03178487, NCT04169373, NCT03569293, NCT03568318, NCT03607422, NCT03345823, NCT02819635.

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Upadacitinib的安全性：超过27,000患者年的类风湿关节炎、银屑病关节炎、轴性脊柱炎、特应性皮炎和炎症性肠病的描述性分析

我们报道了upadacitinib（口服，选择性和可逆的Janus激酶抑制剂）在类风湿关节炎（RA），银屑病关节炎（PsA），强直性脊柱炎（AS），非放射性轴性脊柱炎（nr-axSpA），特应性皮炎（AD），克罗恩病（CD）和溃疡性结肠炎（UC）中的长期安全性。方法：对16项研究的数据进行分析（截止日期为2024年8月15日）。每个治疗组在每个适应症的研究中进行汇总。有效比较组包括阿达木单抗（RA/PsA）和甲氨蝶呤（RA）。治疗中出现的不良事件（teae）报告为每100患者年（n/100 PY）的暴露调整发生率。结果：该分析包括8632例（RA, n = 3209; PsA, n = 907； AS, n = 596; nr-axSpA, n = 286； AD, n = 2683； CD, n = 450； UC, n = 501）更新adacitinib治疗的患者，超过27164.2患者年（适应症范围199.4-12,315.8 PY）。teae的发生率（n/100 PY）在112.0 (AS) ~ 401.1 （RA）之间。最常见的teae报告包括COVID-19、上呼吸道感染、鼻咽炎、带状疱疹、尿路感染和痤疮（主要是AD患者）。严重teae从4.5 （AD）到11.0 （UC）不等，导致停药的teae从2.9 （AS）到8.3 （UC）不等。导致死亡的teae从0 （nr-axSpA， UC）到0.7 （RA）不等。在upadacitinib治疗的不同适应症患者中，特殊不良事件发生率为1.3 - 4.6（严重感染）、2.4-6.6（带状疱疹）、0.2-0.9（恶性肿瘤除外非黑色素瘤皮肤癌[NMSC]）、0-1.4 （NMSC）、0-0.5（主要不良心血管事件[MACE]）、0-0.9（静脉血栓栓塞[VTE]）和0-9.2（肌酸激酶升高）。在RA和PsA中，upadacitinib与活性比较物相比，带状疱疹、NMSC和升高的肌酸激酶率在数值上更高。随着时间的推移，严重感染、带状疱疹、恶性肿瘤（不包括NMSC）、NMSC、MACE和静脉血栓栓塞率保持稳定。结论：这一描述性分析表明upadacitinib的长期安全性与之前的报道一致，进一步支持upadacitinib长期治疗慢性疾病。不同适应症间TEAE发生率的差异可能反映了人群和潜在合并症的差异。试验注册：ClinicalTrials.gov标识号NCT02675426、NCT02706951、NCT02706847、NCT02629159、NCT02706873、NCT03086343、NCT03104374、NCT03104400、NCT03178487、NCT04169373、NCT03569293、NCT03568318、NCT03607422、NCT03345823、NCT02819635。

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来源期刊

Advances in Therapy 医学-药学

CiteScore

7.20

自引率

2.60%

发文量

353

审稿时长

6-12 weeks

期刊介绍： Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) 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 therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in 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.