肿瘤坏死因子抑制剂治疗强直性脊柱炎患者疼痛、疲劳有差别

强直性脊柱炎（AS）是一种使人衰弱的慢性风湿病。其产生的疼痛，疲劳及活动能力的降低严重影响患者生活质量和工作相关活动。

常规的治疗，如非甾体类抗炎药和传统的抗风湿口服药物，疗效并不让人满意。但使用肿瘤坏死因子抑制剂（TNFi）治疗的患者，有高达60％患者大大降低红细胞沉降速率、C反应蛋白，延缓了影像学进展，并改善疼痛和疾病活动评分。

研究目的

尽管TNFi治疗AS效果明显，但TNFi对疼痛和疲劳各自的影响尚不清楚。本研究的目的是观察TNFi治疗对AS患者多种症状缓解的不同影响，重点是疼痛和疲劳。

研究方法

如果疲劳与AS患者的疼痛相关，那么预期使用TNFi治疗时，疲劳会随疼痛减轻而相应地改善。以往的研究表明，AS患者使用TNFi治疗后，无论疼痛缓解的程度如何，疲劳并未见明显改善。因为脑部产生疼痛和疲劳部位不同，我们假设TNFi治疗对疼痛和疲劳的缓解程度不同。为了验证这个假设，我们进行了2项研究：（1）对AS患者进行回顾性研究以确定TNFI治疗对疼痛和疲劳的疗效；（2）AS患者的一项前瞻性脑成像研究，以确定与TNFi相关的大脑变化，特别是与TNFi治疗后疼痛和疲劳变化相关的脑影响。

研究结果

1）对129例使用TNFi治疗AS患者（治疗时间均超过10周）的回顾性研究表明：有60％的患者减轻了疼痛，但总共只有35％的患者疲劳减轻，只有20％的患者在疼痛和疲劳方面均有改善，因此，TNFi对疼痛的治疗要优于疲劳。治疗后，大部分AS患者仍然感到相当程度的疲劳，而疲劳程度可能与患者生活质量有直接关系。

2）14例患者的前瞻性研究表明：基于3T磁共振的脑皮质厚度成像，总的来说：TNFi可能与运动前区和后顶叶显著的皮质变薄相关。减少疼痛强度与次级躯体感觉的皮质萎缩，减少痛苦与不愉快的运动区皮质也是萎缩的。同时，疲劳减轻与胰岛皮质的下壁顶沟也是变薄的。这表明TNFi治疗产生了涉及感觉，运动，情感和认知功能的脑区变化。

研究结论

本研究明确了TNFi对疲劳的有限作用，表现出疼痛和疲劳缓解所使用的不同的脑机制，并提出了在TNFi患者中制定更好的策略应对疲劳，这对于临床药物的开发及药物选择有一定的作用。

参考文献

[1]. Wu, Q., R.D. Inman and K.D. Davis, Tumor necrosis factor inhibitor therapy in ankylosing spondylitis: differential effects on pain and fatigue and brain correlates. Pain, 2015. 156(2): p. 297-304.

原  文

Abstract

Ankylosing spondylitis is associated with back pain and fatigue and impacts mobility but can be treated with tumor necrosis factor inhibitors (TNFi). The differential effects of TNFi treatment on multiple symptoms and the brain is not well delineated. Thus, we conducted a 2-part study. 

In study 1, we conducted a retrospective chart review in 129 ankylosing spondylitis patients to assess TNFi effects on pain, fatigue, motor function, mobility, and quality of life (QoL). After at least 10 weeks of TNFi treatment, patients had clinically significant improvements (>30%) in pain (including neuropathic pain), most disease and QoL factors, and normalized sensory detection thresholds. However, residual fatigue (mean = 5.3) was prominent. Although 60% of patients had significant relief of pain, only 22% of patients had significant relief of both pain and fatigue. Therefore, the preferential TNFi treatment effect on pain compared with fatigue could contribute to suboptimal effects on QoL.

Part 2 was a prospective study in 14 patients to identify TNFi treatment effects on pain, fatigue, sensory and psychological factors, and brain cortical thickness based on 3T magnetic resonance imaging. Centrally, TNFi was associated with statistically significant cortical thinning of motor, premotor, and posterior parietal regions. Pain intensity reduction was associated with cortical thinning of the secondary somatosensory cortex, and pain unpleasantness reduction was associated with the cortical thinning of motor areas. In contrast, fatigue reduction correlated with cortical thinning of the insula, primary sensory cortex/inferior parietal sulcus, and superior temporal polysensory areas. This indicates that TNFi treatment produces changes in brain areas implicated in sensory, motor, affective, and cognitive functions.

翻译：李天旺  江佳伟 广东省第二人民医院风湿免疫科

来源：强直性脊柱炎在线