Furst Daniel E, Weisman Michael, Paulus Harold E, Bulpitt Kenneth, Weinblatt Michael, Polisson Richard, Zaug Michel, Kneer Johannes, Van der Auwera Philippe, Stevens Randall M
Virginia Mason Research Center, Seattle, Washington, USA.
J Rheumatol. 2003 Oct;30(10):2123-6.
To determine the optimal dose regimen of intravenous (IV) Ro 45-2081 (lenercept), a tumor necrosis factor receptor p55-Fc IgG1 fusion protein, in patients with active rheumatoid arthritis (RA) METHODS: In a double-blind, placebo-controlled, parallel-group, multicenter trial, adult patients with long-standing active RA stabilized on conventional therapy were randomly assigned to receive 3 IV infusions, one every 4 weeks, of one of the following: (a) placebo, (b) lenercept 0.01 mg/kg (maximum 1 mg), (c) lenercept 0.05 mg/kg (maximum 5 mg), (d) lenercept 0.2 mg/kg (maximum 20 mg), or (e) lenercept 0.5 mg/kg (maximum 50 mg). The material utilized in the study had a lower relative bioavailability [lower area under the time-concentration curve (AUC) per mg infused] than that used in a recent similar trial. Efficacy variables included change from baseline in number of swollen joints and tender joints, scores on physician and patient assessments of disease activity, and patient assessment of pain.
Patients treated with lenercept exhibited improvement as early as one day after the first IV infusion. The treatment benefit, however, was modest, maximized by 2 weeks and then diminished or vanished as non-neutralizing anti-lenercept antibody concentrations increased. The majority of adverse experiences were mild or moderate and not considered related to study drug.
Our results showed that lenercept administered by IV infusion every 4 weeks is well tolerated, but only transiently effective in patients with long-standing RA, likely due to both the low relative bioavailability of the material used in the study and the formation of non-neutralizing anti-lenercept antibodies.
确定肿瘤坏死因子受体p55-Fc IgG1融合蛋白静脉注射用Ro 45-2081（来那西普）在活动性类风湿关节炎（RA）患者中的最佳给药方案。方法：在一项双盲、安慰剂对照、平行组、多中心试验中，将长期接受传统治疗且病情稳定的成年RA患者随机分为接受以下一种治疗，每4周静脉输注1次，共3次：（a）安慰剂；（b）来那西普0.01 mg/kg（最大剂量1 mg）；（c）来那西普0.05 mg/kg（最大剂量5 mg）；（d）来那西普0.2 mg/kg（最大剂量20 mg）；或（e）来那西普0.5 mg/kg（最大剂量50 mg）。本研究中使用的药物相对生物利用度[每毫克输注药物的时间-浓度曲线下面积（AUC）较低]低于近期一项类似试验中使用的药物。疗效变量包括肿胀关节数和压痛关节数相对于基线的变化、医生和患者对疾病活动度的评估得分以及患者对疼痛的评估。结果：接受来那西普治疗的患者在首次静脉输注后1天就出现改善。然而，治疗益处不大，在2周时达到最大，随后随着非中和性抗来那西普抗体浓度增加而减弱或消失。大多数不良事件为轻度或中度，且不被认为与研究药物有关。结论：我们的结果表明，每4周静脉输注来那西普耐受性良好，但对长期RA患者仅具有短暂疗效，这可能是由于本研究中使用的药物相对生物利用度低以及非中和性抗来那西普抗体的形成。
