The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment - Results of a phase IIb randomized, double-blind, placebo-controlled, dose-ranging trial
The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment - Results of a phase IIb randomized, double-blind, placebo-controlled, dose-ranging trial
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DOI：
10.1002/art.21778
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发表时间：
2006-05-01
影响因子：
--
通讯作者：
Shaw, TM
中科院分区：
文献类型：
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作者：
Emery, P;Fleischmann, R;Shaw, TM
目标。探讨不同剂量的利妥昔单抗联合甲氨蝶呤（MTX）联合或不联合糖皮质激素治疗对包括生物制剂在内的疾病修饰抗风湿药物（DMARDs）有耐药性的活动性类风湿关节炎（RA）患者的疗效和安全性。共有465名患者被随机分为9个治疗组：3个利妥昔单抗组（安慰剂组[n = 149], 500 mg [n = 124]，或1000 mg [n = -192]，在第1天和第15天），每个组同时服用安慰剂糖皮质激素，静脉注射甲基强的松龙药物前，或静脉注射甲基强的松龙药物前加口服强的松，为期2周。所有患者均接受MTX治疗（10- 25mg /周）；不允许使用其他dmard。与安慰剂（28%,P < 0.0001）相比，接受2 500-mg或2 1000 -mg利妥昔单抗输注的患者在第24周达到美国风湿病学会20%改善标准（达到ACR20缓解）的患者显著增加（分别为55%和54%）。ACR50应答率分别为33%、34%和13% (P < 0.001)， ACR70应答率分别为13%、20%和5% （P < 0.05）。28个关节的疾病活动评分（-1.79,-2.05,-0.67;P < 0.0001）和欧洲抗风湿病联盟标准中至良好反应（P < 0.0001）的变化反映了ACR标准的反应。糖皮质激素对24周时的主要疗效终点ACR20反应没有显著贡献。静脉注射糖皮质激素可降低首次输注相关事件的频率和强度；口服糖皮质激素没有额外的安全性益处。利妥昔单抗耐受性良好；感染类型和严重程度与安慰剂组相似。两种剂量的利妥昔单抗在与MTX联合治疗活动性RA患者时均有效且耐受性良好。主要终点（ACR20反应）与糖皮质激素无关，尽管在第一次输注利妥昔单抗期间静脉注射糖皮质激素可改善耐受性。
Objective. To examine the efficacy and safety of different rituximab doses plus methotrexate (MTX), with or without glucocorticoids, in patients with active rheumatoid arthritis (RA) resistant to disease modifying antirheumatic drugs (DMARDs), including biologic agents.Methods. A total of 465 patients were randomized into 9 treatment groups: 3 rituximab groups (placebo [n = 149], 500 mg [n = 124], or 1,000 mg [n = -192] on days 1 and 15) each also taking either placebo glucocorticoids, intravenous methylprednisolone premedication, or intravenous methylprednisolone premedication plus oral prednisone for 2 weeks. All patients received MTX (10-25 mg/week); no other DMARDs were permitted.Results. Significantly more patients who received 2 500-mg or 2 1,000-mg infusions of rituximab met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at week 24 (55% and 54%, respectively) compared with placebo (28%; P < 0.0001). ACR50 responses were achieved by 33%, 34%, and 13% of patients, respectively (P < 0.001), and ACR70 responses were achieved by 13%, 20%, and 5% of patients (P < 0.05). Changes in the Disease Activity Score in 28 joints (-1.79, -2.05, -0.67; P < 0.0001) and moderate to good responses on the European League Against Rheumatism criteria (P < 0.0001) reflected the ACR criteria responses. Glucocorticoids did not contribute significantly to the primary efficacy end point, ACR20 response at 24 weeks. Intravenous glucocorticoid premedication reduced the frequency and intensity of first infusion-associated events; oral glucocorticoids conferred no additional safety benefit. Rituximab was well tolerated; the type and severity of infections was similar to those for placebo.Conclusion. Both rituximab doses were effective and well tolerated when added to MTX therapy in patients with active RA. The primary end point (ACR20 response) was independent of glucocorticoids, although intravenous glucocorticoid premedication improved tolerability during the first rituximab infusion.