Safety and Efficacy of Upadacitinib in Patients with Rheumatoid Arthritis Refractory to Biologic DMARDs: Results Through Week 216 from the SELECT-CHOICE Study.

IF 2.9 3区医学 Q2 RHEUMATOLOGY

Rheumatology and Therapy Pub Date : 2024-10-01 Epub Date: 2024-07-20 DOI:10.1007/s40744-024-00694-x

Andrea Rubbert-Roth, Koji Kato, Boulos Haraoui, Maureen Rischmueller, Yanxi Liu, Nasser Khan, Heidi S Camp, Ricardo M Xavier

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Abstract

Introduction: The safety and efficacy of upadacitinib 15 mg (UPA15) through week 216 was evaluated in patients with rheumatoid arthritis (RA) from the long-term extension (LTE) of the phase 3 SELECT-CHOICE study.

Methods: Patients with RA refractory to biologic disease-modifying antirheumatic drugs (bDMARDs) were randomized to UPA15 or abatacept (ABA) for 24 weeks. During the open-label LTE, patients on ABA switched to UPA15 at week 24, and those on UPA15 continued treatment. The safety and efficacy of continuous UPA15, and ABA to UPA15, are summarized through week 216.

Results: The LTE was comprised of 91.4% (n = 277/303) of patients that initially received UPA15, and 89.6% (n = 277/309) that initially received ABA. Of patients on UPA15 in the LTE (n = 547), 28.3% (n = 155/547) discontinued the study drug by week 216. Relative to other adverse events of special interest, and largely consistent with previous findings at week 24, higher rates of serious infection, COVID-19, herpes zoster, and elevated creatine phosphokinase were reported, while rates of malignancy excluding nonmelanoma skin cancer (NMSC), NMSC, major adverse cardiovascular event (MACE), and venous thromboembolism (VTE) were low. Long-term safety data with UPA through week 216 aligned with previous observations and no new safety risks were identified, including in patients who switched from ABA to UPA15. Proportions of patients achieving 28-joint disease activity score based on C-reactive protein (DAS28[CRP]) < 2.6/ ≤ 3.2, clinical disease activity index (CDAI) and simple disease activity index (SDAI) low disease activity/remission, ≥ 20%/50%/70% improvement in the American College of Rheumatology (ACR20/50/70) response criteria, and Boolean remission were maintained or improved with UPA15 through week 216. Improvements in the Health Assessment Questionnaire-Disability Index (HAQ-DI), patient's assessment of pain, and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were also maintained or improved with UPA15 through week 216. Across all efficacy endpoints, similar results were observed in patients who switched from ABA to UPA15 versus continuous UPA15. Patients with an inadequate response to ≥ 1 prior tumor necrosis factor (TNF) inhibitor (UPA15: n = 263/303, 86.8%; ABA to UPA15: n = 273/309, 88.3%) showed similar responses to the total population.

Conclusions: The long-term safety profile of UPA was consistent with previous findings and the broader RA clinical program. Compared to the primary analyses at week 24, efficacy responses were maintained or further improved with UPA15 through week 216 in patients with RA. Trial registration, ClinicalTrials.gov identifier: NCT03086343.

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奥帕他替尼对生物 DMARDs 难治性类风湿性关节炎患者的安全性和有效性：SELECT-CHOICE 研究第 216 周的结果。

简介在SELECT-CHOICE三期研究的长期延长期（LTE）中，对类风湿性关节炎（RA）患者服用达帕替尼15毫克（UPA15）至第216周的安全性和有效性进行了评估：对生物改善病情抗风湿药（bDMARDs）难治的类风湿关节炎（RA）患者被随机分配到UPA15或阿帕他赛（ABA）治疗24周。在开放标签LTE期间，服用ABA的患者在第24周转为服用UPA15，服用UPA15的患者则继续接受治疗。本文总结了连续使用UPA15和ABA转UPA15治疗到第216周的安全性和疗效：LTE中91.4%（n=277/303）的患者最初接受了UPA15治疗，89.6%（n=277/309）的患者最初接受了ABA治疗。在 LTE 中服用 UPA15 的患者（n = 547）中，28.3%（n = 155/547）在第 216 周前停用了研究药物。与其他特别关注的不良事件相比，第24周时的严重感染、COVID-19、带状疱疹和肌酸磷酸激酶升高的发生率较高，而恶性肿瘤（不包括非黑色素瘤皮肤癌）、非黑色素瘤皮肤癌、主要不良心血管事件（MACE）和静脉血栓栓塞（VTE）的发生率较低，这与之前的研究结果基本一致。截至第216周的UPA长期安全性数据与之前的观察结果一致，没有发现新的安全性风险，包括从ABA转为UPA的患者15。根据C反应蛋白（DAS28[CRP]）得出28关节疾病活动度评分的患者比例结论：UPA的长期安全性与之前的研究结果和更广泛的RA临床项目一致。与第24周时的主要分析结果相比，UPA15在第216周时对RA患者的疗效反应得到了维持或进一步改善。试验注册，ClinicalTrials.gov 标识符：NCT03086343。

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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. 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