Objective

Osteoarthritis (OA) is characterized by the gradual loss of cartilage. Sprifermin, a recombinant FGF18, is being developed as a cartilage anabolic drug. PRO-C2 is a serum marker of type II collagen formation and low levels have been shown to be prognostic of radiographic progression. The aim of the study was to investigate whether the patient groups with either high or low PRO-C2 levels responded differently to sprifermin.

Design

PRO-C2 was measured in synovial fluid (SF) (n = 59) and serum samples (n = 225) from participants of the FORWARD study, a 2-year phase IIb clinical trial testing the efficacy of intra-articular (IA) sprifermin over placebo. The difference between sprifermin and placebo in respect to in change cartilage thickness (measured by quantitative (q) MRI) was analyzed in groups with either high or low (3^rd vs 1^st-2^nd tertiles) baseline serum PRO-C2 levels.

Results

SF levels of PRO-C2 increased over time in response to sprifermin, but not to placebo. In the placebo arm, significantly (p = 0.005) more cartilage was lost in the low vs high PRO-C2 group over the 2-year period. The contrast between sprifermin and placebo was significant (p < 0.001), ranging from 0.104 mm at week 26 to 0.229 mm at week 104 in the low PRO-C2 group. This result was not significant in the high PRO-C2 group ranging from −0.034 to 0.142.

Conclusions

Patients with low serum PRO-C2 levels lost more cartilage thickness over time and grew more cartilage in response to sprifermin vs a placebo when compared to patients with high PRO-C2 levels.

中文翻译：

---

低水平的 II 型胶原蛋白形成 (PRO-C2) 与对 sprifermin 的反应相关：来自 FORWARD 研究的预定义探索性生物标志物分析

客观的

骨关节炎 (OA) 的特征是软骨逐渐丧失。Sprifermin 是一种重组 FGF18，正在开发为一种软骨合成代谢药物。PRO-C2 是 II 型胶原形成的血清标志物，低水平已被证明是放射学进展的预后。该研究的目的是调查 PRO-C2 水平高或低的患者组对 sprifermin 的反应是否不同。

设计

PRO-C2 是在 FORWARD 研究参与者的滑液 (SF) ( n  = 59) 和血清样本 ( n  = 225) 中测量的，这是一项为期 2 年的 IIb 期临床试验，用于测试关节内 (IA) sprifermin 的功效超过安慰剂。在基线血清 PRO-C2 水平高或低（3 ^rd vs 1 -2 ^{nd三分位数）的组中分析了sprifermin}和安慰剂在改变软骨厚度（通过定量 (q) MRI 测量）方面的差异。

结果

对 sprifermin 的反应，PRO-C2 的 SF 水平随时间增加，但对安慰剂没有反应。在安慰剂 组中，在 2 年期间，低 PRO-C2 组与高 PRO-C2 组的软骨损失显着 ( p = 0.005) 更多。sprifermin 和安慰剂之间的对比是显着的 ( p  < 0.001)，在低 PRO-C2 组中从第 26 周的 0.104 mm 到第 104 周的 0.229 mm 不等。这一结果在 -0.034 至 0.142 的高 PRO-C2 组中不显着。

结论

与高 PRO-C2 水平的患者相比，血清 PRO-C2 水平低的患者随着时间的推移失去更多的软骨厚度，并且与安慰剂相比，对 sprifermin 的反应使软骨生长更多。