Low levels of type II collagen formation (PRO-C2) are associated with response to sprifermin: a pre-defined, exploratory biomarker analysis from the FORWARD study
Low levels of type II collagen formation (PRO-C2) are associated with response to sprifermin: a pre-defined, exploratory biomarker analysis from the FORWARD study
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DOI：
10.1016/j.joca.2021.10.008
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发表时间：
2021-12-22
影响因子：
7
通讯作者：
Ladel, C.
中科院分区：
文献类型：
--
作者：
Bay-Jensen, A. C.;Manginelli, A. A.;Ladel, C.
目的：骨关节炎（OA）是一种以软骨逐渐丧失为特征的疾病。Sprifermin是一种重组FGF 18，正在开发作为软骨合成代谢药物。PRO-C2是II型胶原蛋白形成的血清标志物，低水平已被证明是放射学进展的预后指标。该研究的目的是调查具有高或低PRO-C2水平的患者组对sprifermin的反应是否不同。设计图：在FORWARD研究参与者的滑液（SF）（n = 59）和血清样本（n = 225）中测量PRO-C2，FORWARD研究是一项为期2年的IIb期临床试验，旨在测试关节内（IA）sprifermin相对于安慰剂的疗效。在具有高或低（第3个与第1个和第2个三分位数）基线血清PRO-C2水平的组中分析sprifermin和安慰剂之间关于软骨厚度变化（通过定量（q）MRI测量）的差异。结果：SF PRO-C2水平随时间增加，对sprifermin有反应，但对安慰剂无反应。在安慰剂组中，在2年期间，低PRO-C2组与高PRO-C2组相比，软骨丢失显著更多（p = 0.005）。sprifermin和安慰剂之间的对比是显著的（p < 0.001），在低PRO-C2组中，范围从第26周的0.104 mm到第104周的0.229 mm。高PRO-C2组中该结果不显著，范围为-0.034至0.142。结论：与具有高PRO-C2水平的患者相比，具有低血清PRO-C2水平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，响应于sprifermin生长更多的软骨。(c)2021年，任作家。由Elsevier Ltd代表国际骨关节炎研究协会出版。这是一个在CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/bync-nd/4.0/）。
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 (3rd vs 1st2nd 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. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).