Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Ann Rheum Dis. 2012 May;71(5):687-93. doi: 10.1136/annrheumdis-2011-200395. Epub 2011 Nov 25.
Treatment with tumour necrosis factor inhibitors (TNF-i) plus methotrexate (MTX), but not MTX monotherapy alone, inhibits joint damage progression even at higher levels of disease activity. Such disassociation of disease activity and structural damage has not been shown for biological agents other than TNF-i.
To evaluate whether interleukin 6 (IL-6) inhibition with tocilizumab (TCZ) interferes with joint destruction beyond its effects on disease activity.
A random 90% sample of data from the (The Tocilizumab Safety and the Prevention of Structural Joint Damage Study) LITHE trial on active rheumatoid arthritis (RA) despite MTX was used, which compared addition of placebo (n=117) with addition of TCZ (n=414) every 4 weeks. Baseline and 1-year values of clinical and serological variables were correlated with changes to 1 year of the total Genant-modified Sharp score (TGSS) using a Spearman test, and the progression of TGSS, erosion and joint space narrowing (JSN) scores in groups with low and high disease activity were compared for placebo and TCZ (Kruskal-Wallis).
Baseline variables were similar among the groups. Change of TGSS was lower in patients receiving TCZ than placebo (TCZ: 0.29 ± 0.96; placebo: 0.90 ± 1.92; p=0.0007). In patients receiving placebo, the correlation with TGSS change was significant for baseline scores of the simplified disease activity index (SDAI; r=0.18, p=0.047) and swollen joint count 28 (r=0.22, p=0.019), with similar trends for C-reactive protein. Similar correlations were seen for SDAI, clinical disease activity index, disease activity score 28 at 1 year with x-ray change during that year (r=0.26-0.28, p=0.002-0.006). In contrast, none of the baseline or 1-year variables showed significant correlation with x-ray changes in patients receiving TCZ+MTX, suggesting a disassociation of the link between disease activity and damage by TCZ. Finally, for patients in remission or with low disease activity, progression of TGSS, erosion and JSN was similar among treatment groups (TGSS: placebo, 0.4±1.1; TCZ, 0.2 ± 0.7; p=NS), while for patients with moderate or high disease activity placebo-treated patients progression was significantly greater (TGSS: 1.2 ± 2.2 vs 0.4 ± 1.2; p=0.0009).
IL-6 inhibition with TCZ plus MTX retards joint damage progression independently of its impact on disease activity. Similar effects have hitherto been reported only for TNF-i. This indicates that the effects of IL-6 inhibition on progression of joint damage in RA are among the most profound currently attainable.
肿瘤坏死因子抑制剂（TNF-i）联合甲氨蝶呤（MTX）治疗，而不是单独使用 MTX，即使在疾病活动度较高的情况下，也能抑制关节损伤的进展。除 TNF-i 外，尚未有其他生物制剂显示出疾病活动度和结构损伤之间的这种分离。
评估白细胞介素 6（IL-6）抑制是否会干扰托珠单抗（TCZ）的关节破坏，超出其对疾病活动度的影响。
使用来自活动性类风湿关节炎（RA）的托西珠单抗安全性和预防结构关节损伤研究（LITHE 试验）的随机 90%样本数据，该试验比较了安慰剂（n=117）与 TCZ（n=414）每 4 周添加一次的效果。使用 Spearman 检验将基线和 1 年的临床和血清学变量与 1 年总 Genant 改良 Sharp 评分（TGSS）的变化相关联，并比较低和高疾病活动度组中安慰剂和 TCZ 治疗的 TGSS、侵蚀和关节间隙狭窄（JSN）评分的进展（Kruskal-Wallis）。
各组间基线变量相似。与安慰剂相比，TCZ 治疗患者的 TGSS 变化较低（TCZ：0.29±0.96；安慰剂：0.90±1.92；p=0.0007）。在接受安慰剂的患者中，简化疾病活动指数（SDAI）的基线评分（r=0.18，p=0.047）和肿胀关节计数 28（r=0.22，p=0.019）与 TGSS 变化有显著相关性，C 反应蛋白也有类似的趋势。对于 SDAI、临床疾病活动指数和 1 年时的疾病活动评分 28，与该年内的 X 射线变化相关的相似趋势（r=0.26-0.28，p=0.002-0.006）。相比之下，在接受 TCZ+MTX 的患者中，没有任何基线或 1 年的变量与 X 射线变化有显著相关性，表明 TCZ 可分离疾病活动度与损伤之间的联系。最后，对于缓解或低疾病活动度的患者，治疗组之间 TGSS、侵蚀和 JSN 的进展相似（TGSS：安慰剂，0.4±1.1；TCZ，0.2±0.7；p=NS），而对于中或高疾病活动度的患者，安慰剂治疗患者的进展明显更大（TGSS：1.2±2.2 vs 0.4±1.2；p=0.0009）。
IL-6 抑制联合 MTX 可延迟关节损伤的进展，而与疾病活动度的影响无关。类似的效果迄今为止仅在 TNF-i 中报道过。这表明，IL-6 抑制对 RA 关节损伤进展的影响是目前最显著的。
Zotero 插件