Kennedy Institute of Rheumatology Division, Imperial College, London, UK.
Ann Rheum Dis. 2011 Dec;70(12):2119-25. doi: 10.1136/ard.2011.151522. Epub 2011 Aug 22.
To evaluate the efficacy and safety of intravenous ofatumumab, a fully human anti-CD20 monoclonal antibody, in biological-naive, active rheumatoid arthritis (RA) patients despite methotrexate treatment.
In this double-blind, placebo-controlled, phase III study, active RA patients on stable methotrexate were randomly assigned to one course of two infusions of ofatumumab 700 mg (n=130) or placebo (n=130), 2 weeks apart. The primary endpoint was the ACR20 response at week 24. Secondary endpoints included ACR50/70, EULAR response, disease activity score based on 28 joints using C-reactive protein, adverse events (AE) and immunogenicity.
At week 24, a greater proportion of patients on ofatumumab compared with placebo achieved an ACR20 response (50% vs 27%, p<0.001) and a good or moderate EULAR response (67% vs 41%, p<0.001). All other key secondary efficacy endpoints were significantly improved on ofatumumab. Efficacy observed by 8 weeks was sustained throughout the study. The most common AE for ofatumumab versus placebo were rash (21% vs <1%) and urticaria (12% vs <1%), mostly occurring on the first infusion day. Overall, first-dose infusion reactions were 68% for ofatumumab and 6% for placebo, mostly mild to moderate; second-dose infusion reactions markedly declined (<1% and 0%). Serious AE were reported in 5% of ofatumumab versus 3% of placebo patients. Infection rates were 32% and 26% (serious infections <1% and 2%), respectively. One death (interstitial lung disease), unrelated to study drug, was reported on ofatumumab. No antidrug antibodies were detected in ofatumumab patients.
Ofatumumab significantly improved all clinical outcomes in biological-naive, active RA patients with no detectable immunogenicity at week 24. No unexpected safety findings were identified. Trial Registry clinical trials.gov registration number NCT00611455.
评估完全人源抗 CD20 单克隆抗体奥法木单抗静脉制剂在生物初治、活动性类风湿关节炎（RA）患者中的疗效和安全性，这些患者尽管接受了甲氨蝶呤治疗。
在这项双盲、安慰剂对照、III 期研究中，稳定接受甲氨蝶呤治疗的活动性 RA 患者被随机分配至接受两剂奥法木单抗 700mg（n=130）或安慰剂（n=130）治疗，每 2 周 1 次。主要终点是第 24 周时的 ACR20 应答。次要终点包括 ACR50/70、EULAR 应答、基于 C 反应蛋白的 28 个关节疾病活动评分、不良事件（AE）和免疫原性。
在第 24 周时，与安慰剂相比，更多的奥法木单抗治疗患者达到 ACR20 应答（50% vs 27%，p<0.001）和良好或中度 EULAR 应答（67% vs 41%，p<0.001）。奥法木单抗治疗的所有其他关键次要疗效终点均显著改善。在整个研究过程中，第 8 周观察到的疗效得以维持。奥法木单抗最常见的 AE 与安慰剂相比为皮疹（21% vs <1%）和荨麻疹（12% vs <1%），主要发生在第 1 次输注日。奥法木单抗的总体首剂量输注反应为 68%，而安慰剂为 6%，多为轻度至中度；第 2 次剂量输注反应显著下降（<1%和 0%）。奥法木单抗组有 5%的患者报告出现严重 AE，而安慰剂组为 3%。奥法木单抗组的感染率为 32%，安慰剂组为 26%（严重感染率分别为<1%和 2%）。奥法木单抗组报告了 1 例死亡（间质性肺病），与研究药物无关。奥法木单抗组未检测到抗药物抗体。
奥法木单抗显著改善了生物初治、活动性 RA 患者的所有临床结局，在第 24 周时未检测到免疫原性。未发现新的安全性发现。试验注册临床试验.gov 注册号 NCT00611455。
