University of Montreal, Montreal, Quebec, Canada.
J Rheumatol. 2011 Dec;38(12):2548-56. doi: 10.3899/jrheum.110444. Epub 2011 Oct 1.
To evaluate the safety and effectiveness of rituximab (RTX) in combination with methotrexate in patients with active rheumatoid arthritis (RA) after failure of a single tumor necrosis factor-α (TNF-α) inhibitor. Changes in patient-reported outcomes after primary treatment or retreatment with RTX and factors determining retreatment in clinical practice were also evaluated.
In this phase 3b open-label, multicenter trial, patients received 2 slow infusions of RTX 1000 mg 14 days apart after premedication (primary treatment). Patients with a clinically relevant response could receive retreatment between 24 and 48 weeks. The primary endpoint was evaluation of safety. Secondary outcomes were safety of retreatment, effectiveness of primary treatment and retreatment, and changes in patient-reported outcomes after primary treatment or retreatment.
Of 120 patients enrolled at 36 centers and receiving primary RTX treatment, 77 received retreatment, 112 completed the 24-week primary treatment period, and 25 completed the 48-week primary treatment and retreatment period following a single course of RTX. The most common adverse events were mild to moderate nausea, vomiting, nasopharyngitis, and headache. No infections or infusion reactions were considered life-threatening. At 24 weeks, 58%, 27%, and 7% of patients achieved American College of Rheumatology 20, 50, and 70 improvements, respectively, and similar improvements were seen after retreatment.
RTX was well tolerated, with a low incidence of infusion reactions and infections. Efficacy results, including enhanced response in rheumatoid factor-positive patients, were comparable to those reported in the literature. Based on its efficacy and safety profile and retreatment schedule, RTX is an attractive treatment option for patients that have not responded to a single TNF-α inhibitor.
评估利妥昔单抗（RTX）联合甲氨蝶呤治疗 TNF-α 抑制剂单一治疗失败的活动期类风湿关节炎（RA）患者的安全性和有效性。还评估了患者在初次治疗或 RTX 补救治疗后的报告结局变化，以及临床实践中决定补救治疗的因素。
在这项 3b 期开放标签、多中心试验中，患者在预处理后接受 2 次 RTX 1000mg 的缓慢输注，间隔 14 天（初次治疗）。具有临床相关反应的患者可以在 24 至 48 周之间接受补救治疗。主要终点是评估安全性。次要终点是补救治疗的安全性、初次治疗和补救治疗的有效性，以及初次治疗或补救治疗后患者报告结局的变化。
在 36 个中心招募了 120 名接受初次 RTX 治疗的患者，其中 77 名接受了补救治疗，112 名完成了 24 周的初次治疗期，25 名在单次 RTX 治疗后完成了 48 周的初次治疗和补救治疗期。最常见的不良事件为轻度至中度恶心、呕吐、鼻咽炎和头痛。没有发生危及生命的感染或输注反应。24 周时，分别有 58%、27%和 7%的患者达到美国风湿病学会 20、50 和 70 改善标准，补救治疗后也观察到类似的改善。
RTX 耐受性良好，输注反应和感染发生率低。疗效结果，包括对类风湿因子阳性患者的增强反应，与文献报道的结果相当。基于其疗效和安全性特征以及补救治疗方案，RTX 是一种对未对 TNF-α 抑制剂产生应答的患者具有吸引力的治疗选择。
