Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin; Department of Gastroenterology, Infectiology and Rheumatology (including Nutrition Medicine), Hindenburgdamm 30, 12203 Berlin, Germany; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Anna-Louisa-Karsch-Str. 2, 10178 Berlin, Germany; German Rheumatism Research Centre, Berlin, Germany, Virchowweg 12, 10117 Berlin, Germany.
Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands.
Semin Arthritis Rheum. 2022 Apr;53:151974. doi: 10.1016/j.semarthrit.2022.151974. Epub 2022 Feb 2.
To analyze whether biomarker levels at baseline or their change after 3 months or 2 years predict radiographic spinal progression in ankylosing spondylitis (AS) patients treated with TNF-α inhibitors (TNFi).
137 AS patients from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort were included before starting TNFi. Serum biomarkers were measured at baseline, 3 months and 2 years: Markers of inflammation (calprotectin, matrix metalloproteinase-3, vascular endothelial growth factor), bone turnover markers (bone-specific alkaline phosphatase, serum C-terminal telopeptide fragments of type I collagen (sCTX), osteocalcin, osteoprotegerin, procollagen type I and II N-terminal propeptide, sclerostin) and adipokines (high-molecular-weight adiponectin, leptin, visfatin). Spinal radiographs were scored at baseline, 2 and 4 years. Logistic regression was performed to examine the association between biomarker values and radiographic spinal progression, adjusting for known risk factors for radiographic progression.
Baseline calprotectin and visfatin levels were associated with mSASSS progression ≥2 points (OR 1.195 [95%CI 1.055-1.355] and 1.465 [1.137-1.889], respectively), while calprotectin was also associated with new syndesmophyte formation after 2 years (OR 1.107 [1.001-1.225]). Baseline leptin level was associated with mSASSS progression ≥4 points after 4 years (OR 0.614 [0.453-0.832]), and baseline sCTX level with syndesmophyte formation after 4 years (OR 1.004 [1.001-1.008]). Furthermore, change of visfatin and leptin levels over the first 2 years showed significant association with radiographic progression after 4 years.
Independent of known risk factors, serum levels of biomarkers at baseline are able to predict radiographic spinal progression over 2 and 4 years in AS patients on TNFi therapy.
分析基线时的生物标志物水平或治疗开始后 3 个月或 2 年的变化是否可预测接受 TNF-α 抑制剂（TNFi）治疗的强直性脊柱炎（AS）患者的放射学脊柱进展。
在开始使用 TNFi 之前，从格罗宁根-吕伐登轴向脊柱关节炎（GLAS）队列中纳入了 137 名 AS 患者。基线、3 个月和 2 年时检测血清生物标志物：炎症标志物（钙卫蛋白、基质金属蛋白酶-3、血管内皮生长因子）、骨转换标志物（骨碱性磷酸酶、I 型胶原 C 端肽血清片段（sCTX）、骨钙素、骨保护素、I 型和 II 型前胶原 N 端肽、骨桥蛋白）和脂肪细胞因子（高分子量脂联素、瘦素、内脂素）。基线、2 年和 4 年时对脊柱 X 线片进行评分。采用逻辑回归分析生物标志物值与放射学脊柱进展之间的关系，同时调整放射学进展的已知危险因素。
基线钙卫蛋白和内脂素水平与 mSASSS 进展≥2 分相关（比值比 1.195[95%CI 1.055-1.355]和 1.465[1.137-1.889]），而钙卫蛋白也与 2 年后新的骨桥形成相关（比值比 1.107[1.001-1.225]）。基线瘦素水平与 4 年后 mSASSS 进展≥4 分相关（比值比 0.614[0.453-0.832]），而基线 sCTX 水平与 4 年后骨桥形成相关（比值比 1.004[1.001-1.008]）。此外，前 2 年的内脂素和瘦素水平变化与 4 年后的放射学进展有显著相关性。
独立于已知的危险因素，在接受 TNFi 治疗的 AS 患者中，基线时的生物标志物水平可预测 2 年和 4 年时的放射学脊柱进展。
