在类风湿性关节炎 (RA) 患者中，持续炎症和疾病活动性增加与不良事件 (AE) 风险增加相关。旨在评估接受托法替布或肿瘤坏死因子抑制剂 (TNFi) 治疗的患者中 RA 疾病活动性与感兴趣的 AE 之间的关系）。这是对托法替布与 TNFi 的长期、授权后安全性终点试验的事后分析。在口腔监测中，4362 名 50 岁以上的患者尽管服用了甲氨蝶呤，但仍患有活动性 RA，并且有 1 个额外的心血管 (CV) 危险因素，按 1:1:1 的比例随机分配至托法替布 5 或 10mg，每日两次或 TNFi，持续长达 72 个月。事后时间依赖性多变量 Cox 分析评估了疾病活动性 [临床疾病活动指数 (CDAI)]、炎症 [C 反应蛋白 (CRP)] 和感兴趣的 AE 之间的关系。 AE 包括主要不良心血管事件 (MACE)、不包括非黑色素瘤皮肤癌 (NMSC) 的恶性肿瘤、静脉血栓栓塞 (VTE)、严重感染、带状疱疹 (HZ)、不包括带状疱疹的非严重感染 (NSI) 和死亡。当患者患有 CDAI 定义的活动性疾病时，与缓解患者相比，NSI 更高； MACE 和 VTE 风险呈上升趋势，但并未达到显着水平。血清 CRP 每增加 5 mg/L，MACE、不包括 NMSC、VTE 的恶性肿瘤、感染和死亡的风险比就会上升 2-9%。评估治疗分配对疾病活动性和 AE 之间关系的影响的交互项均为 p > 0.05。在口腔监测中，与缓解期相比，活动性 RA 存在时观察到更高的 NSI 风险。与缓解期相比，活动性疾病中 MACE 和 VTE 的风险定向增加，尽管由于这些类别中的事件数量较少，统计功效有限。托法替布与 TNFi 治疗相比，活动性疾病与 AE 之间的关系并未受到影响。NCT02092467.© 作者，2023 年。

In patients with rheumatoid arthritis (RA), persistent inflammation and increasing disease activity are associated with increased risk of adverse events (AEs).To assess relationships between RA disease activity and AEs of interest in patients treated with tofacitinib or tumor necrosis factor inhibitors (TNFi).This was a post hoc analysis of a long-term, postauthorization safety endpoint trial of tofacitinib versus TNFi.In ORAL Surveillance, 4362 patients aged ⩾50 years with active RA despite methotrexate, and ⩾1 additional cardiovascular (CV) risk factor, were randomized 1:1:1 to tofacitinib 5 or 10 mg twice daily or TNFi for up to 72 months. Post hoc time-dependent multivariable Cox analysis evaluated the relationships between disease activity [Clinical Disease Activity Index (CDAI)], inflammation [C-reactive protein (CRP)], and AEs of interest. The AEs included major adverse CV events (MACE), malignancies excluding nonmelanoma skin cancer (NMSC), venous thromboembolism (VTE), serious infections, herpes zoster (HZ), nonserious infections excluding HZ (NSI), and death.Across treatments, risk for NSI was higher when patients had CDAI-defined active disease versus remission; MACE and VTE risks trended higher, but did not reach significance. Hazard ratios for MACE, malignancies excluding NMSC, VTE, infections, and death rose by 2-9% for each 5-mg/L increment in serum CRP. The interaction terms evaluating the impact of treatment assignment on the relationship between disease activity and AEs were all p > 0.05.In ORAL Surveillance, higher NSI risk was observed in the presence of active RA versus remission. The risk of MACE and VTE directionally increased in active disease versus remission, although statistical power was limited due to small event numbers in these categories. The relationship between active disease and AEs was not impacted by treatment with tofacitinib versus TNFi.NCT02092467.© The Author(s), 2023.