在一项3期临床试验（DISCOVER-2）中，胶原蛋白周转生物标志物与活动性银屑病关节炎相关，且随着古塞库单抗治疗而降低。
Collagen Turnover Biomarkers Associate with Active Psoriatic Arthritis and Decrease with Guselkumab Treatment in a Phase 3 Clinical Trial (DISCOVER-2).
作者信息
Schett Georg, Loza Matthew J, Palanichamy Arumugam, FitzGerald Oliver, Ritchlin Christopher, Bay-Jensen Anne-Christine, Nielsen Signe Holm, Gao Sheng, Hsia Elizabeth C, Kollmeier Alexa P, Xu Xie L, Baribaud Frédéric, Sweet Kristen
机构信息
Department of Internal Medicine 3, Friedrich Alexander University Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Janssen Research & Development LLC, Spring House, PA, USA.
出版信息
Rheumatol Ther. 2022 Aug;9(4):1017-1030. doi: 10.1007/s40744-022-00444-x. Epub 2022 Mar 30.
INTRODUCTION
Guselkumab, a novel interleukin-23p19 subunit monoclonal antibody, has been shown to effectively improve the diverse manifestations of active psoriatic arthritis (PsA) in two phase 3 trials (DISCOVER-1, DISCOVER-2). Serum concentrations of extracellular matrix (ECM) biomarkers at baseline and following treatment with guselkumab were evaluated in patients with active PsA, and the relationship of these biomarkers with baseline PsA characteristics and clinical response to guselkumab treatment was explored.
METHODS
Serum samples were collected at weeks 0, 4, 24, and 52 from a selected subset (N = 260) of the 739 biologic-naïve patients with PsA treated with guselkumab 100 mg every 4 or 8 weeks or placebo in DISCOVER-2. Demographically matched healthy controls (N = 76) were used for comparison. The samples were analyzed for ECM biomarkers associated with collagen degradation (C1M, C2M, C3M, C4M, C6M, C10C) and collagen formation (PRO-C1, PRO-C2, PRO-C3, PRO-C4, PRO-C6).
RESULTS
Baseline concentrations of collagen degradation biomarkers C1M, C3M, C4M, and C6M and collagen formation biomarkers PRO-C3 and PRO-C6 were significantly higher (i.e., ≥ 1.25-fold and false discovery rate adjusted p < 0.05) in PsA patients than in healthy controls. Serum C1M, C3M, C4M, and C6M levels declined from baseline in guselkumab-treated patients in both dosing regimens. In addition, guselkumab-treated ACR20 responders (≥ 20% improvement in American College of Rhematology response criteria) had significantly lower C1M levels than ACR20 nonresponders.
CONCLUSION
These data demonstrate that serum collagen biomarkers are elevated in patients with PsA compared with healthy controls and that treatment with guselkumab decreases levels of C1M, C3M, C4M, and C6M. Importantly, C1M serves as a biomarker that associates with improvement of joint signs and symptoms.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT03158285.
引言
古塞库单抗是一种新型白细胞介素-23p19亚基单克隆抗体，在两项3期试验（DISCOVER-1、DISCOVER-2）中已显示能有效改善活动性银屑病关节炎（PsA）的多种表现。对活动性PsA患者在基线时以及接受古塞库单抗治疗后的细胞外基质（ECM）生物标志物血清浓度进行了评估，并探讨了这些生物标志物与基线PsA特征以及对古塞库单抗治疗临床反应之间的关系。
方法
在DISCOVER-2中，从739例初治生物制剂的PsA患者中选取一个子集（N = 260），每4周或8周接受100 mg古塞库单抗或安慰剂治疗，分别在第0、4、24和52周采集血清样本。使用人口统计学匹配的健康对照（N = 76）进行比较。对样本分析与胶原降解相关的ECM生物标志物（C1M、C2M、C3M、C4M、C6M、C10C）和胶原形成相关的生物标志物（PRO-C1、PRO-C2、PRO-C3、PRO-C4、PRO-C6）。
结果
PsA患者中胶原降解生物标志物C1M、C3M、C4M和C6M以及胶原形成生物标志物PRO-C3和PRO-C6的基线浓度显著高于（即≥1.25倍且错误发现率调整后p < 0.05）健康对照。在两种给药方案中，接受古塞库单抗治疗的患者血清C1M、C3M、C4M和C6M水平均较基线下降。此外，达到美国风湿病学会（ACR）20反应标准（改善≥20%）的接受古塞库单抗治疗的患者C1M水平显著低于ACR20无反应者。
结论
这些数据表明，与健康对照相比，PsA患者血清胶原生物标志物升高，且古塞库单抗治疗可降低C1M、C3M、C4M和C6M水平。重要的是，C1M可作为与关节体征和症状改善相关的生物标志物。
试验注册
ClinicalTrials.gov标识符：NCT
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