Intraarticular Sprifermin (Recombinant Human Fibroblast Growth Factor 18) in Knee Osteoarthritis
Intraarticular Sprifermin (Recombinant Human Fibroblast Growth Factor 18) in Knee Osteoarthritis
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DOI：
10.1002/art.38614
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发表时间：
2014-07-01
影响因子：
13.3
通讯作者：
Eckstein, Felix
中科院分区：
文献类型：
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作者：
Lohmander, L. Stefan;Hellot, Scarlett;Eckstein, Felix
Objective.评价关节腔内注射重组人成纤维细胞生长因子18（sprifermin）治疗症状性膝骨关节炎（OA）的疗效和安全性。该研究是一项随机、双盲、安慰剂对照、概念验证试验。以10 μ g、30 μ g和100 μ g的剂量评价关节内sprifermin。主要疗效终点是使用定量磁共振成像（qMRI）确定的6个月和12个月时中央内侧股胫间室软骨厚度的变化。主要安全性终点是局部和全身治疗后出现的不良事件（AE）和急性炎症反应的性质、发生率和严重程度，以及实验室评估结果。次要终点包括通过qMRI评估的总股胫软骨厚度和体积的变化、X线片上观察到的关节间隙宽度（JSW）的变化以及西安大略和麦克马斯特大学骨关节炎指数（WOMAC）的疼痛评分。192例患者被随机分组并进行安全性评价，180例完成了试验，168例接受了主要疗效终点评价。我们发现，在中央内侧股胫间室软骨厚度的变化中，没有统计学显著的剂量反应。Sprifermin与总和外侧股胫软骨厚度和体积的损失以及外侧股胫间室JSW狭窄的统计学显著性、剂量依赖性减少相关。所有组的WOMAC疼痛评分均有所改善，与接受安慰剂的患者相比，接受100 μ g剂量sprifermin的患者在12个月时的改善程度在统计学上显著降低。Sprifermin组和安慰剂组在严重不良事件、治疗后出现的不良事件或急性炎症反应方面无显著差异。未观察到治疗组与中央内侧股胫间室软骨厚度减少之间存在统计学显著性关系;然而，预先规定的结构次要终点显示sprifermin治疗后统计学显著性剂量依赖性减少。Sprifermin与任何局部或全身安全性问题无关。
Objective. To evaluate the efficacy and safety of intraarticular sprifermin (recombinant human fibroblast growth factor 18) in the treatment of symptomatic knee osteoarthritis (OA).Methods. The study was a randomized, double-blind, placebo-controlled, proof-of-concept trial. Intraarticular sprifermin was evaluated at doses of 10 mu g, 30 mu g, and 100 mu g. The primary efficacy end point was change in central medial femorotibial compartment cartilage thickness at 6 months and 12 months as determined using quantitative magnetic resonance imaging (qMRI). The primary safety end points were nature, incidence, and severity of local and systemic treatment-emergent adverse events (AEs) and acute inflammatory reactions, as well as results of laboratory assessments. Secondary end points included changes in total and compartment femorotibial cartilage thickness and volume as assessed by qMRI, changes in joint space width (JSW) seen on radiographs, and pain scores on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).Results. One hundred ninety-two patients were randomized and evaluated for safety, 180 completed the trial, and 168 were evaluated for the primary efficacy end point. We found no statistically significant dose response in change in central medial femorotibial compartment cartilage thickness. Sprifermin was associated with statistically significant, dose-dependent reductions in loss of total and lateral femorotibial cartilage thickness and volume and in JSW narrowing in the lateral femorotibial compartment. All groups had improved WOMAC pain scores, with statistically significantly less improvement at 12 months in patients receiving the 100-mu g dose of sprifermin as compared with those receiving placebo. There was no significant difference in serious AEs, treatment-emergent AEs, or acute inflammatory reactions between sprifermin and placebo groups.Conclusion. No statistically significant relation-ship between treatment group and reduction in central medial femorotibial compartment cartilage thickness was observed; however, prespecified structural secondary end points showed statistically significant dose-dependent reductions after sprifermin treatment. Sprifermin was not associated with any local or systemic safety concerns.