托珠单抗能否降低长期类风湿性关节炎患者的软骨寡聚基质蛋白水平及疾病活动度？

Can tocilizumab decrease cartilage oligomeric matrix protein levels and disease activity in patients with long-standing rheumatoid arthritis?

作者信息

Benucci Maurizio, Meacci Francesca, Manfredi Mariangela, Gobbi Francesca Li, Infantino Maria, Ricci Cristian, Sarzi-Puttini Piercarlo, Atzeni Fabiola

机构信息

Rheumatology Unit, Azienda Sanitaria di Firenze, Hospital S. Giovanni di Dio, Via Torregalli 3, 50143 Firenze FI, Italy.

出版信息

Curr Rheumatol Rev. 2014;10(2):131-5. doi: 10.2174/1573397111666150113215950.

DOI:10.2174/1573397111666150113215950

PMID:25599685

Abstract

Serum cartilage oligomeric matrix protein (COMP) level is a new marker of joint destruction in patients with rheumatoid arthritis (RA), and a new means of identifying patients with progressive joint damage. To evaluate the effect of tocilizumab (TCZ) on serum COMP levels, and whether there is any difference in this effect between patients failing on anti-TNF treatment and those failing on disease-modifying anti-rheumatic drugs (DMARDs). Fifty-one patients with long-standing RA (42 F, 9 M; mean age 62 ± 14 years; disease duration 4.5 ± 1.2 years) unresponsive to DMARDs and anti-TNF drugs were treated with TCZ 8 mg/kg/month. Serum COMP levels were measured by means of an ELISA at baseline and after six months of TCZ treatment; the patents' DAS28 scores and levels of RF (IgM, IgG, IgA), anti-CCP autoantibodies, ESR, CRP and IL-6 were evaluated at the same times. After six months of TCZ treatment, there was a significant decrease from baseline in ESR (46.1 [28.7-68.9] vs 34.3 [4.1- 58.8] mm/h, P <0.0001), CRP (2.2 [0.8-4.4] vs 1.3 [0.7-3.8] mg/dL, P <0.0001), TNF-α (21.3 [7.6-29.8] vs 17.4 [3.4-28.6] pg/mL, P=0.0408), IL-6 (6.9 [3.5-9.6] vs 3.4 [3.0-9.6] pg/mL, p<0.0001); anti-CCP (55.1 [30.2-273.0] vs 54.7 [30.1- 269.8] IU/mL, P=0.9683), RF-IgM (142.0 [48.0-260.0] vs 138.0 [42.0-243.0] IU/mL, P=0.4828), RF-IgA (81.0 [20-140] vs 108.0 [20-175] U/mL, P=0.0003), and RF-IgG (65.2 [30-158] vs 58.3 [38.0-158.0] U/mL, P=0.2671). There was also a significant decrease in DAS28 scores (4.3 [3.2-5.9] vs 3.7 [2.3-5.4], P <0.0001), and a non-significant decrease in serum COMP levels (0.95 [0.04-2.90] vs 0.98 [0.05-2.36] μg/mL; P = 0.9856). A decrease in serum COMP levels was observed in the patients failing on anti-TNF treatment or anti-DMARDs without any difference. TCZ therapy in patients with long-standing RA is associated with a significant decrease in ESR, CRP, IL-6, TNF and DAS28 values, and a decrease in serum COMP levels, particularly in patients failing on previous anti-TNF therapy. These findings suggest that TCZ has an effect on cartilage joint destruction after only six months of treatment.

摘要

血清软骨寡聚基质蛋白（COMP）水平是类风湿关节炎（RA）患者关节破坏的一种新标志物，也是识别进行性关节损伤患者的一种新方法。为评估托珠单抗（TCZ）对血清COMP水平的影响，以及在抗TNF治疗失败的患者和抗风湿药物（DMARDs）治疗失败的患者中这种影响是否存在差异。51例对DMARDs和抗TNF药物无反应的长期RA患者（42例女性，9例男性；平均年龄62±14岁；病程4.5±1.2年）接受8mg/kg/月的TCZ治疗。在基线和TCZ治疗6个月后通过酶联免疫吸附测定法（ELISA）测量血清COMP水平；同时评估患者的DAS28评分以及RF（IgM、IgG、IgA）、抗环瓜氨酸肽自身抗体、红细胞沉降率（ESR）、C反应蛋白（CRP）和白细胞介素-6的水平。TCZ治疗6个月后，ESR较基线显著下降（46.1[28.7 - 68.9]对比34.3[4.1 - 58.8]mm/h，P<0.0001），CRP（2.2[0.8 - 4.4]对比1.3[0.7 - 3.8]mg/dL，P<0.0001），肿瘤坏死因子-α（TNF-α）（21.3[7.6 - 29.8]对比17.4[3.4 - 28.6]pg/mL，P = 0.0408），白细胞介素-6（IL-6）（6.9[3.5 - 9.6]对比3.4[3.0 - 9.6]pg/mL，P<0.0001）；抗环瓜氨酸肽（anti-CCP）（55.1[30.2 - 273.0]对比54.7[30.1 - 269.8]IU/mL，P = 0.9683），RF-IgM（142.0[48.0 - 260.0]对比138.0[42.0 - 243.0]IU/mL，P = 0.4828），RF-IgA（81.0[20 - 140]对比108.0[20 - 175]U/mL，P = 0.0003），以及RF-IgG（65.2[30 - 158]对比58.3[38.0 - 158.0]U/mL，P = 0.2671）。DAS28评分也显著下降（4.3[3.2 - 5.9]对比3.7[2.3 - 5.4]，P<0.0001），血清COMP水平有不显著下降（0.95[0.04 - 2.90]对比0.98[0.05 - 2.36]μg/mL；P = 0.9856）。在抗TNF治疗失败或抗DMARDs治疗失败的患者中均观察到血清COMP水平下降，且无差异。长期RA患者接受TCZ治疗与ESR、CRP、IL-6、TNF以及DAS28值显著下降相关，血清COMP水平也下降，尤其是既往抗TNF治疗失败的患者。这些发现表明，TCZ仅治疗6个月就对软骨关节破坏有影响。