Mount Sinai Hospital and the University of Toronto, Toronto, Ontario, Canada.
J Rheumatol. 2012 Dec;39(12):2238-46. doi: 10.3899/jrheum.120573. Epub 2012 Oct 1.
This 5-year observational posthoc analysis of the REFLEX study and its open-label extension assessed clinical efficacy, radiographic response, and safety of rituximab (RTX) in patients with rheumatoid arthritis (RA) who had an inadequate response to tumor necrosis factor (TNF) inhibitors.
Patients in REFLEX were originally randomized to placebo (PBO) + methotrexate (MTX; PBO-randomized) or RTX + MTX (RTX-randomized). PBO-randomized patients were rescued with RTX as appropriate. Patients responding to initial RTX treatment could receive further RTX courses. For clinical efficacy and safety analyses, PBO-randomized patients were re-baselined prior to first RTX treatment and the data were pooled with RTX-randomized patient data. Efficacy outcomes 24 weeks after each course were calculated relative to first RTX pretreatment baseline. Radiographic outcomes were assessed relative to randomization baseline for both PBO-randomized and RTX-randomized groups.
A total of 480 patients received ≥ 1 RTX course. At 24 weeks, American College of Rheumatology 20/50/70 responses were 62.0%, 30.8%, and 13.0%, respectively at course 1 (n = 400) and 70.3%, 41.8%, and 22.0% at course 5 (n = 91). European League Against Rheumatism good/moderate responses were 77.2% and 84.4% at courses 1 (n = 390) and 5 (n = 90). Rates of adverse events (AE), serious AE, and infections generally remained stable. Rate of progressive joint damage (PJD; change in mean Total Sharp Score) decreased over time in both PBO-randomized (n = 79) and RTX-randomized (n = 105) groups. Mean change from baseline in PJD over 5 years was greater in PBO-randomized versus RTX-randomized patients (5.51 vs 3.21).
RTX re-treatment over 5 years is associated with maintained or improved efficacy, continued inhibition of PJD, and a safety profile consistent with that previously reported. A delay in initiating RTX treatment may result in increased PJD.
这项 REFLEX 研究的 5 年观察性事后分析及其开放标签扩展评估了在对肿瘤坏死因子 (TNF) 抑制剂反应不足的类风湿关节炎 (RA) 患者中，利妥昔单抗 (RTX) 的临床疗效、放射学反应和安全性。
REFLEX 中的患者最初被随机分配至安慰剂 (PBO) + 甲氨蝶呤 (MTX; PBO 随机化) 或 RTX + MTX (RTX 随机化)。PBO 随机化的患者根据需要接受 RTX 解救治疗。对初始 RTX 治疗有反应的患者可以接受进一步的 RTX 疗程。对于临床疗效和安全性分析，在接受首次 RTX 治疗之前，PBO 随机化的患者重新进行基线评估，并将数据与 RTX 随机化患者的数据进行汇总。在每个疗程后 24 周，根据首次 RTX 预处理基线计算疗效终点。对于 PBO 随机化和 RTX 随机化两组，均根据随机化基线评估放射学结果。
共有 480 名患者接受了 ≥ 1 次 RTX 疗程。在第 1 个疗程 (n = 400) 时，第 24 周时美国风湿病学会 20/50/70 缓解率分别为 62.0%、30.8%和 13.0%，在第 5 个疗程 (n = 91) 时分别为 70.3%、41.8%和 22.0%。第 1 个疗程 (n = 390) 和第 5 个疗程 (n = 90) 时，欧洲抗风湿病联盟的良好/中度缓解率分别为 77.2%和 84.4%。不良事件 (AE)、严重 AE 和感染的发生率通常保持稳定。在 PBO 随机化 (n = 79) 和 RTX 随机化 (n = 105) 两组中，关节进展性损害 (PJD；总 Sharp 评分均值的变化) 率随时间推移而降低。5 年内 PBO 随机化与 RTX 随机化患者的 PJD 自基线的平均变化值分别为 5.51 和 3.21。
5 年内重复 RTX 治疗与疗效的维持或改善、持续抑制 PJD 以及与既往报告一致的安全性相关。延迟开始 RTX 治疗可能导致 PJD 增加。
