Østergaard Mikkel, Emery Paul, Conaghan Philip G, Fleischmann Roy, Hsia Elizabeth C, Xu Weichun, Rahman Mahboob U
Department of Rheumatology, Copenhagen University Hospital at Glostrup, Glostrup, Denmark.
Arthritis Rheum. 2011 Dec;63(12):3712-22. doi: 10.1002/art.30592.
To evaluate the effects of golimumab on inflammation/structural damage detected by magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA).
Methotrexate (MTX)-naive RA patients (n = 637) were randomized to placebo plus MTX, golimumab 100 mg plus placebo, golimumab 50 mg plus MTX, or golimumab 100 mg plus MTX (subcutaneous golimumab every 4 weeks). Of these, 318 patients participated in an MRI substudy. MRIs (contrast-enhanced; 1.5T) of the wrist and second through fifth metacarpophalangeal joints of the dominant hand were obtained at baseline and weeks 12 and 24. MRIs were scored by 2 independent readers (blinded to image sequence/chronology, patient identity, and treatment group) for synovitis, bone edema/osteitis, and bone erosions using the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) system. Radiographs (hands, wrists, forefeet at baseline and week 28) were scored by 2 other readers (blinded as above) using the modified Sharp/van der Heijde (SvdH) scoring system. Changes from baseline were compared between treatment groups (two-sided analysis of variance on van der Waerden normal scores).
At weeks 12 and 24, combined therapy with golimumab plus MTX versus placebo plus MTX significantly improved RAMRIS scores for synovitis (mean -1.92 versus 0.14 [P < 0.001] at week 12; -2.45 versus -1.04 [P < 0.001] at week 24), osteitis (mean -1.82 versus 0.56 [P < 0.001] at week 12; -2.27 versus -0.32 [P < 0.001] at week 24), and bone erosion (mean -0.40 versus 0.24 [P = 0.016] at week 12; -0.40 versus -0.24 [P = 0.010] at week 24). Results of sensitivity analyses (no missing doses/data and using linear extrapolation) were generally consistent with results of the primary analyses. Changes in SvdH scores among the MRI substudy patients at week 28 showed no significant difference between golimumab plus MTX therapy and placebo plus MTX (mean 0.49 versus 0.92; P = 0.19). Radiographic SvdH scores demonstrated inhibition of structural damage progression by treatment with golimumab plus MTX as compared with placebo plus MTX in the overall study population but required double the number of patients (637 versus 318) and double the length of followup (28 versus 12 weeks) as needed for MRI to demonstrate this.
Improvements in inflammation (synovitis and osteitis) and erosions with golimumab plus MTX therapy exceeded those with placebo plus MTX therapy from week 12 onward, confirming the overall clinical/radiologic findings. MRI was more sensitive than conventional radiography in detecting the progression of erosions.
评估戈利木单抗对类风湿关节炎（RA）患者磁共振成像（MRI）检测到的炎症/结构损伤的影响。
未使用过甲氨蝶呤（MTX）的RA患者（n = 637）被随机分为安慰剂加MTX组、100 mg戈利木单抗加安慰剂组、50 mg戈利木单抗加MTX组或100 mg戈利木单抗加MTX组（每4周皮下注射戈利木单抗）。其中，318例患者参与了MRI子研究。在基线、第12周和第24周时，对优势手的腕关节以及第二至第五掌指关节进行MRI检查（增强扫描；1.5T）。由2名独立阅片者（对图像序列/时间顺序、患者身份和治疗组不知情）使用类风湿关节炎磁共振成像评分（RAMRIS）系统对滑膜炎、骨水肿/骨炎和骨侵蚀进行评分。另外2名阅片者（同样不知情）使用改良的夏普/范德海伊德（SvdH）评分系统对基线和第28周时的手部、腕部、前足X线片进行评分。比较各治疗组相对于基线的变化（对范德瓦尔登正态分数进行双侧方差分析）。
在第12周和第24周时，戈利木单抗加MTX联合治疗组与安慰剂加MTX组相比，滑膜炎的RAMRIS评分显著改善（第12周时，平均分别为-1.92和0.14 [P < 0.001]；第24周时，-2.45和-1.04 [P < 0.001]），骨炎评分（第12周时，平均分别为-1.82和0.56 [P < 0.001]；第24周时，-2.27和-0.32 [P < 0.001]），以及骨侵蚀评分（第12周时，平均分别为-0.40和0.24 [P = 0.016]；第24周时，-0.40和-0.24 [P = 0.010]）。敏感性分析结果（无漏用剂量/数据且使用线性外推法）与主要分析结果基本一致。在MRI子研究患者中，第28周时SvdH评分的变化显示，戈利木单抗加MTX治疗组与安慰剂加MTX组之间无显著差异（平均分别为0.49和0.92；P = 0.19）。在整个研究人群中，与安慰剂加MTX相比，戈利木单抗加MTX治疗显示出对结构损伤进展的抑制作用，但X线片SvdH评分需要的患者数量是MRI的两倍（637例对318例），随访时间也是MRI的两倍（28周对12周）才能显示出这一结果。
从第12周起，戈利木单抗加MTX治疗在炎症（滑膜炎和骨炎）及侵蚀方面的改善超过了安慰剂加MTX治疗，证实了总体临床/放射学研究结果。在检测侵蚀进展方面，MRI比传统X线摄影更敏感。
