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首页> 外文期刊>Osteoarthritis and cartilage >Safety, tolerability, and pharmacodynamics of an anti-interleukin-1α/β dual variable domain immunoglobulin in patients with osteoarthritis of the knee: a randomized phase 1 study
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Safety, tolerability, and pharmacodynamics of an anti-interleukin-1α/β dual variable domain immunoglobulin in patients with osteoarthritis of the knee: a randomized phase 1 study

机译：患者骨关节炎患者抗白细胞介素-1α/β双可变域免疫球蛋白的安全性，耐受性和药效学：随机阶段1研究

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Summary Objective To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABT-981, a human dual variable domain immunoglobulin simultaneously targeting interleukin (IL)-1α and IL-1β, in patients with knee osteoarthritis (OA). Method This was a randomized, double-blind, placebo-controlled, single-center study of multiple subcutaneous (SC) injections of ABT-981 in patients with mild-to-moderate OA of the knee (NCT01668511). Three cohorts received ABT-981 (0.3, 1, or 3?mg/kg) or placebo every other week for a total of four SC injections, and one cohort received ABT-981 (3?mg/kg) or placebo every 4 weeks for a total of three SC injections. Assessment of safety and tolerability were the primary objectives. A panel of serum and urine biomarkers of inflammation and joint degradation were evaluated. Results A total of 36 patients were randomized (ABT-981, n ?=?28; placebo, n ?=?8); 31 (86%) completed the study. Adverse event (AE) rates were comparable between ABT-981 and placebo (54% vs 63%). The most common AE reported with ABT-981 vs placebo was injection site erythema (14% vs 0%). ABT-981 significantly reduced absolute neutrophil count and serum concentrations of IL-1α/IL-1β, high-sensitivity C-reactive protein, and matrix metalloproteinase (MMP)-derived type 1 collagen. Serum concentrations of MMP-derived type 3 collagen and MMP-degraded C-reactive protein demonstrated decreasing trends with ABT-981. Antidrug antibodies were found in 37% of patients but were not associated with the incidence or severity of AEs. Conclusion ABT-981 was generally well tolerated in patients with knee OA and engaged relevant tissue targets, eliciting an anti-inflammatory response. Consequently, ABT-981 may provide clinical benefit to patients with inflammation-driven OA.
机译：发明内容目的探讨ABT-981的安全性，耐受性，药代动力学和药效学，人双可变域免疫球蛋白同时靶向白细胞介素（IL）-1α和IL-1β，患者患者膝关节骨关节炎（OA）。方法这是膝关节温和至中等OA的患者对ABT-981的多个皮下（SC）注射的随机，双盲，安慰剂，单中心研究（NCT01668511）。三个队列每隔一周收到ABT-981（0.3,1或3×mg / kg）或安慰剂，总共四个SC注射，每4周收到ABT-981（3？Mg / kg）或安慰剂总共三个SC注射。评估安全性和耐受性是主要目标。评估了血清和尿液生物标志物的炎症和关节降解。结果共有36名患者随机（ABT-981，N？28;安慰剂，N？8）; 31（86％）完成了这项研究。 ABT-981和安慰剂之间的不良事件（AE）率可比较（54％vs 63％）。随着ABT-981 VS安慰剂报告的最常见的AE是注射部位红斑（14％Vs 0％）。 ABT-981显着降低了IL-1α/ IL-1β，高灵敏度C-反应蛋白的绝对中性粒细胞计数和血清浓度和基质金属蛋白酶（MMP）的1型胶原蛋白。 MMP衍生的3型胶原和MMP降解的C反应蛋白的血清浓度证明了ABT-981的趋势降低。在37％的患者中发现了抗抗皱抗体，但与AES的发病率或严重程度无关。结论ABT-981通常在膝关节OA患者中耐受良好耐受，相关组织靶标，引发抗炎反应。因此，ABT-981可以向炎症驱动的OA患者提供临床益处。

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