多生物标志物疾病活动评分对早期类风湿关节炎患者临床缓解和影像学进展的预测价值：OPERA试验的事后分析
Predictive value of a multi-biomarker disease activity score for clinical remission and radiographic progression in patients with early rheumatoid arthritis: a post-hoc study of the OPERA trial.
作者信息
Brahe C H, Østergaard M, Johansen J S, Defranoux N, Wang X, Bolce R, Sasso E H, Ørnbjerg L M, Hørslev-Petersen K, Stengaard-Pedersen K, Junker P, Ellingsen T, Ahlquist P, Lindegaard H, Linauskas A, Schlemmer A, Dam M Y, Hansen I, Lottenburger T, Ammitzbøll C, Jørgensen A, Krintel S B, Raun J, Hetland M L
机构信息
a Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet , Glostrup , Denmark.
b Department of Clinical Medicine , University of Copenhagen , Copenhagen , Denmark.
出版信息
Scand J Rheumatol. 2019 Jan;48(1):9-16. doi: 10.1080/03009742.2018.1464206. Epub 2018 Jul 9.
OBJECTIVES
Measurement of serum biomarkers at disease onset may improve prediction of disease course in patients with early rheumatoid arthritis (RA). We evaluated the multi-biomarker disease activity (MBDA) score and early changes in MBDA score for prediction of 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) remission and radiographic progression in the double-blinded OPERA trial.
METHOD
Treatment-naïve RA patients (N = 180) with moderate or high DAS28 were randomized to methotrexate (MTX) + adalimumab (n = 89) or MTX + placebo (n = 91) in combination with glucocorticoid injection into swollen joints. X-rays of hands and feet were evaluated at months 0 and 12 (n = 164) by the total Sharp van der Heijde score (TSS). The smallest detectable change (1.8 TSS units) defined radiographic progression (∆TSS ≥ 2). Clinical remission (DAS28-CRP < 2.6) was assessed at baseline and 6 months. MBDA score was determined at 0 and 3 months and tested in a multivariable logistic regression model for predicting DAS28 remission at 6 months and radiographic progression at 1 year.
RESULTS
Baseline MBDA score was independently associated with radiographic progression at 1 year [odds ratio (OR) = 1.03/unit, 95% confidence interval (CI) = 1.01-1.06], and changes in MBDA score from baseline to 3 months with clinical remission at 6 months [OR = 0.98/unit, 95% CI 0.96-1.00). In anti-cyclic citrullinated peptide antibody (anti-CCP)-positive patients, 35 of 89 with high MBDA score (> 44) showed radiographic progression (PPV = 39%), compared with 0 of 15 patients (NPV = 100%) with low/moderate MBDA score (≤ 44) (p = 0.003).
CONCLUSION
Early changes in MBDA score were associated with clinical remission based on DAS28-CRP at 6 months. In anti-CCP-positive patients, a non-high baseline MBDA score (≤ 44) had a clinical value by predicting very low risk of radiographic progression at 12 months.
目的
在疾病发作时测量血清生物标志物可能会改善早期类风湿关节炎（RA）患者疾病进程的预测。在双盲OPERA试验中，我们评估了多生物标志物疾病活动（MBDA）评分以及MBDA评分的早期变化，以预测基于C反应蛋白的28关节疾病活动评分（DAS28-CRP）缓解情况和影像学进展。
方法
未接受过治疗、DAS28为中度或高度的RA患者（N = 180）被随机分为甲氨蝶呤（MTX）+ 阿达木单抗组（n = 89）或MTX + 安慰剂组（n = 91），并联合对肿胀关节进行糖皮质激素注射。在第0个月和第12个月对164例患者的手和脚进行X线检查，采用总Sharp van der Heijde评分（TSS）评估。最小可检测变化（1.8个TSS单位）定义为影像学进展（∆TSS≥2）。在基线和6个月时评估临床缓解情况（DAS28-CRP < 2.6）。在第0个月和第3个月测定MBDA评分，并在多变量逻辑回归模型中进行测试，以预测6个月时的DAS28缓解情况和1年时的影像学进展。
结果
基线MBDA评分与1年时的影像学进展独立相关[比值比（OR）= 1.03/单位，95%置信区间（CI）= 1.01 - 1.06]，从基线到3个月MBDA评分的变化与6个月时的临床缓解相关[OR = 0.98/单位，95% CI 0.96 - 1.00]。在抗环瓜氨酸肽抗体（抗CCP）阳性患者中，89例MBDA评分高（> 44）的患者中有35例出现影像学进展（阳性预测值 = 39%），而15例MBDA评分低/中度（≤ 44）的患者中无一例出现影像学进展（阴性预测值 = 100%）（p = 0.003）。
结论
MBDA评分的早期变化与6个月时基于DAS28-CRP的临床缓解相关。在抗CCP阳性患者中，非高基线MBDA评分（≤ 44）通过预测12个月时影像学进展的极低风险具有临床价值。
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