Ann Rheum Dis：长期抗TNF治疗或不增加新骨生成

　　来自德国的一项研究显示，连续长期使用抗肿瘤坏死因子（TNF）治疗并不使强直性脊柱炎患者8年来新骨生成率增加。研究者认为，尽管患者数量和回顾性研究设计存在局限性，但这些数据表明接受抗TNF治疗的患者和那些不使用抗TNF治疗的患者新骨生成有所增加。然而，由于INF治疗组8年后新骨生成非常少，所以这些数据反对TNF-闸假说（the TNF-brake hypothesis）的重要作用。该论文于2013年3月16在线发表在《风湿病年鉴》[Ann Rheum Dis]。

　　该研究是比较使用英夫利昔单抗（INF）治疗强直性脊柱炎患者和未使用抗肿瘤坏死因子阻滞剂治疗的历史对照（HC）8年来的影像学进展。

　　研究者根据有基线时和8年后的颈腰椎侧位影像摄片来选择患者。两位双盲读片医生使用改良Stokes强直性脊柱炎脊柱评分（mSASSS）对影像摄片进行评分。校正基线状态后，应用混合线性模型比较两队列影像摄片进展。

　　结果是，INF（n=22例）和HC（n=34例）组的患者mSASSS状态并无不同（13.2 对14.2，P=0.254）。两组8年时（摄片）进展为：INF组平均mSASSS为20.2，HC为25.9。校正基线损伤后，INF组8年时平均mSASSS为21.0，HC为25.5（P=0.047）。两组平均mSASSS差异在基线时和4年时相似，但在4年和8年时，HC组差异更明显（P=0.03）。平均韧带骨赘数尽管在基线时相似，但在8年时明显不同：INF组每例患者新韧带骨赘数为1.0，HC为2.7（P=0.007）。校正基线时年龄、症状持续时间、HLA-B27、Bath强直性脊柱炎疾病活动指数和Bath强直性脊柱炎功能指数后，（两组韧带骨赘数）均不受影响。

与强直性脊柱炎相关的拓展阅读：

• Nat Genet：强直性脊柱炎新易感基因位点被发现

Continuous long-term anti-TNF therapy does not lead to an increase in the rate of new bone formation over 8 years in patients with ankylosing spondylitis

Objective 

Compare the radiographic progression of ankylosing spondylitis (AS) patients treated with infliximab (INF) versus historical controls (Herne cohort, HC) never treated with tumour necrosis factor (TNF)-blockers over 8 years.

Methods 

Patients were selected based on the availability of lateral cervical and lumbar radiographs at baseline (BL) and after 8 years. Radiographs were scored by two blinded readers using modified Stokes AS spinal score (mSASSS). Mixed linear models were applied to compare radiographic progression between cohorts after adjustment for baseline status.

Results 

Patients in INF (n=22) and HC (n=34) did not differ in the mSASSS status: 13.2±17.6 in INF versus 14.2±13.8 in HC (p=0.254). Both showed progression at 8 years: mean mSASSS 20.2±21.4 in INF and 25.9±17.8 in HC. After adjustment for baseline damage the mean mSASSS (SEM) at 8 years was 21.0 (1.4) in INF and 25.5 (1.1) HC (p=0.047). The mean mSASSS difference was similar in the groups between baseline and 4 years but was more pronounced in HC between 4 and 8 years (p=0.03 between groups). The mean number of syndesmophytes, although similar at baseline, differed significantly at 8 years: 1.0±0.6 new syndesmophytes/patient in INF versus 2.7±0.8 in HC (p=0.007). Adjustment for age, symptom duration, HLA-B27, Bath AS disease activity index and Bath AS function index at baseline had no influence.

Conclusions 

Despite limitations of patient numbers and retrospective study design, these data show increase in new bone formation in both patients treated with anti-TNF and those who did not. However, since there was even less bone formation in the INF treated group after 8 years, these data argue against a major role for the TNF-brake hypothesis.