背景:在3期选择选择研究的长期延长(LTE)的类风湿关节炎(RA)患者中评估了15mgupadacitinib(UPA15)至216周的安全性和有效性。
方法:接受生物疾病缓解抗风湿药(bDMARDs)治疗的RA患者随机接受UPA15或abatacept(ABA)治疗24周。在开放标签LTE期间,ABA患者在第24周转为UPA15,UPA15患者继续治疗.连续UPA15和ABA至UPA15的安全性和有效性总结到第216周。
结果:LTE由91.4%(n=277/303)的最初接受UPA15的患者和89.6%(n=277/309)的最初接受ABA的患者组成。LTE中UPA15的患者(n=547),28.3%(n=155/547)在第216周停止研究药物。相对于其他特别关注的不良事件,与之前在第24周的发现基本一致,严重感染率更高,COVID-19,带状疱疹,据报道肌酸磷酸激酶升高,而不包括非黑色素瘤皮肤癌(NMSC)的恶性肿瘤发生率,NMSC,主要不良心血管事件(MACE),静脉血栓栓塞症(VTE)较低。UPA至第216周的长期安全数据与之前的观察结果一致,没有发现新的安全风险。包括从ABA转换为UPA15的患者。根据C反应蛋白(DAS28[CRP])<2.6/≤3.2,临床疾病活动指数(CDAI)和简单疾病活动指数(SDAI)低疾病活动/缓解,达到28关节疾病活动评分的患者比例,美国风湿病学会(ACR20/50/70)反应标准改善≥20%/50%/70%,通过UPA15至第216周,布尔缓解得以维持或改善。健康评估问卷-残疾指数(HAQ-DI)的改进,患者对疼痛的评估,在第216周,UPA15也维持或改善了慢性疾病治疗-疲劳的功能评估(FACIT-F)。在所有疗效终点,与连续UPA15相比,在从ABA转换为UPA15的患者中观察到相似的结果.对≥1种先前的肿瘤坏死因子(TNF)抑制剂(UPA15:n=263/303,86.8%;ABA对UPA15:n=273/309,88.3%)的反应不足的患者与总人口相似。
结论:UPA的长期安全性与先前的发现和更广泛的RA临床计划一致。与第24周的主要分析相比,RA患者在第216周使用UPA15维持或进一步改善了疗效反应。试用登记,ClinicalTrials.gov标识符:NCT03086343。
一项长期研究着眼于一种名为upadacitinib的药物,用于治疗类风湿关节炎(RA)。引起关节疼痛和损伤的疾病。该研究包括其他可注射药物未改善RA的患者。该研究比较了upadacitinib与另一种名为abatacept的药物。24周后,服用abatacept的患者改用upadacitinib,服用upadacitinib的患者继续接受upadacitinib治疗超过4年.研究人员研究了这些治疗方法的长期效果以及是否有任何副作用。在这项长期研究中,upadacitinib治疗的副作用与先前使用upadacitinib的研究中报道的副作用相似。研究人员还发现,随着时间的推移,upadacitinib有助于减轻RA的症状,帮助患者完成日常活动,减轻疼痛和疲劳。对于24周后从abatacept转为upadacitinib的患者以及从研究开始服用upadacitinib的患者,情况都是如此。对其他药物没有反应的患者使用upadacitinib也有类似的改善。总之,upadacitinib可以长期帮助RA患者,没有发现新的安全风险.
BACKGROUND: 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.
A long-term study looked at a drug named upadacitinib to treat people with rheumatoid arthritis (RA), a disease that causes joint pain and damage. The study included patients whose RA was not improved by other injectable medicines. The study compared upadacitinib with another drug called abatacept. After 24 weeks, patients who were taking abatacept switched to upadacitinib, and patients taking upadacitinib continued on upadacitinib treatment for over 4 years. The researchers looked at how well the treatments worked over the long-term and if there were any side effects. The side effects with upadacitinib treatment in this long-term study were similar to side effects reported in previous studies with upadacitinib. The researchers also found that upadacitinib helped to lessen the symptoms of RA over time and helped patients complete their daily activities and reduced their pain and tiredness. This was true for patients who switched from abatacept to upadacitinib after 24 weeks and for patients who took upadacitinib from the start of the study. Patients who had not responded to other medicines also had similar improvements with upadacitinib. In conclusion, upadacitinib can help people with RA over the long term and no new safety risks were found.