Avdeeva A S, Aleksandrova E N, Novikov A A, Cherkasova M V, Panasyuk E Yu, Nasonov E L
Ter Arkh. 2013;85(5):24-9.
To evaluate the impact of tocilizumab (TCZ) therapy on the level of matrix metalloproteinase-3 (MMP-3) 4, 24, and 48 weeks after treatment initiation in relation to the clinical efficiency of TCZ therapy by the Disease Activity Score (DAS28), the Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI).
Forty-two rheumatoid arthritis (RA) patients who had received 6 intravenous infusions of TCZ 8 mg/kg at a 4-week interval during permanent therapy with disease-modifying anti-rheumatic drugs (DMARD) and glucocorticosteroids (GCS) were examined. Then TCZ was discontinued and the patients continued to receive the previous therapy with DMARD and GCS. The European League Against Rheumatism (EULAR) classification criteria, as well as SDAI and CDAI were used to evaluate the efficiency of TCZ therapy. The serum concentration of MMP-3 was measured by enzyme immunoassay using the test systems (Invitrogen, USA).
After 24 weeks of TCZ therapy (at 48 weeks following trial initiation), DAS28 was 4.69 (3.86; 5.44); the SDAI of 17.8 (10.7; 29.5) and the CDAI of 17.1 (7.2; 26.2) corresponded to moderate disease activity. At 48 weeks, DAS28 remission (< 2.6 scores) remained in 5 (11.90%) patients; SDAI (< or = 3.3 scores) and CDAI (< or = 2.8 scores) remissions did in 3 (7.1%) and 4 (9.5%) patients, respectively. There was a significant reduction in MMP-3 concentrations at 4, 24, and 48 weeks of the therapy, which was 61, 73, and 49.40% of the baseline level. ROC analysis indicated that the normalization of MMP-3 levels in RA patients at 24 weeks of TCZ therapy (a cut-off < or =16.5 ng/ml) was associated with the maintenance of remission/low disease activity from SDAI and CDAI 24 weeks after the drug use (the area under the receiver operating curve was 0.762; 95% confidence interval: 0.548-0.976).
Analysis of the results of 48-week TCZ therapy suggests its ability to reduce the levels of markers of bone and cartilage destruction in patients with RA. Serum MMP-3 determination at 24 weeks of therapy may be useful in predicting the maintenance of remission/low activity from SDAI and CDAI after discontinuation of the drug.
评估托珠单抗（TCZ）治疗开始后4周、24周和48周时，基质金属蛋白酶-3（MMP-3）水平的变化，并通过疾病活动评分（DAS28）、临床疾病活动指数（CDAI）和简化疾病活动指数（SDAI）来分析TCZ治疗的临床疗效。
对42例类风湿关节炎（RA）患者进行研究，这些患者在接受改善病情抗风湿药（DMARD）和糖皮质激素（GCS）的长期治疗期间，每隔4周静脉输注6次8mg/kg的TCZ。之后停用TCZ，患者继续接受DMARD和GCS的先前治疗。采用欧洲抗风湿病联盟（EULAR）分类标准以及SDAI和CDAI来评估TCZ治疗的疗效。使用美国Invitrogen公司的检测系统，通过酶免疫测定法测量血清MMP-3浓度。
TCZ治疗24周后（试验开始后48周），DAS28为4.69（3.86；5.44）；SDAI为17.8（10.7；29.5），CDAI为17.1（7.2；26.2），均对应中度疾病活动。48周时，5例（11.90%）患者达到DAS28缓解（<2.6分）；分别有3例（7.1%）和4例（9.5%）患者达到SDAI（≤3.3分）和CDAI（≤2.8分）缓解。治疗4周、24周和48周时，MMP-3浓度显著降低，分别为基线水平的61%、73%和49.40%。ROC分析表明，TCZ治疗2周时RA患者MMP-3水平正常化（临界值≤16.5ng/ml）与用药24周后SDAI和CDAI维持缓解/低疾病活动相关（受试者工作特征曲线下面积为0.762；95%置信区间：0.548 - 0.976）。
对48周TCZ治疗结果的分析表明，其能够降低RA患者骨和软骨破坏标志物的水平。治疗24周时测定血清MMP-3可能有助于预测停药后SDAI和CDAI维持缓解/低活动状态。
