摘要
目的观察延长TNF-α抑制剂的使用间隔时间是否可以持续改善或维持SpA患者的炎症指标和骶髂关节、脊柱的影像学评分。方法收集154例SpA患者，95例接受TNF-α抑制剂治疗，减量方案如下：依那西普每1、2、3、4周50 mg皮下注射，英夫利西单抗第0、2、6周4 mg/kg至每8、12、16周4 mg/kg静脉滴注，阿达木单抗每2、3、4、8周40 mg皮下注射。3~6个月评估患者的炎症指标、骶髂关节骨髓水肿加拿大脊柱关节炎研究协会（SPARCC）评分，二分类法评估脂肪沉积、骨侵蚀、硬化和关节强直，第2年采用改良Stoke强直性脊柱炎脊柱评分（mSASSS）评估颈腰椎放射片。治疗前后计量资料使用配对t检验或Wilcoxon非参数检验，2组或3组计量资料采用Mann-Whitney U或Kruskal-Wallis非参数检验，计数资料采用χ2检验。结果经过足量TNF-α抑制剂治疗，SpA患者3~6个月的ESR、CRP、IgA、BASDAI、BASFI、AS疾病活动评分（ASDAS）和SPARCC评分比治疗前明显改善[分别为13.00（6.00，31.00）mm/1 h，3.00（2.00，6.00）mm/1 h，Z=-5.61；7.39（2.52，17.90）mg/L，1.88（1.21，3.75）mg/L，Z=-5.57；2.89（2.52，17.90）g/L，2.27（1.60，2.85）g/L，Z=-4.69；2.6±1.4，1.2±0.9，t=9.81；17.50（5.00，27.00），4.00（0，11.00），Z=-6.69；2.62（2.02，3.52），1.22（0.92，1.59），Z=-6.96；25.00（10.00，37.00），12.00（6.00，20.25），Z=-6.68；P均〈0.05]。与第3~6个月比较，患者第2~3年的骶髂关节骨髓水肿明显降低，差异具有统计学意义[12.00（6.00，20.25），7.00（3.25，14.75），Z=-2.48，P=0.01]。与非TNF-α抑制剂治疗组比较，TNF-α抑制剂治疗组第2~3年骶髂关节脂肪沉积、骨侵蚀、硬化和关节强直的发生率差异无统计学意义（分别为61%，57%，χ2=0.07，P=1.00；53%，43%，χ2=0.40，P=0.75；31%，57%，χ2=3.02，P=0.11；14%，7%，χ2=0.43，P=0.66），2组患者治疗后的脊柱mSASSS评分差异也无统计学意义[2.50（0，8.00），3.00（0，8.00），Z=-0.30，P=0.76]。结论采用不断延长TNF-α抑制剂使用间隔时间的减量方案可以持续改善骶髂关节骨髓水肿，并且不增加骶髂关节和脊柱的结构性病变。
ObjectiveTo investigate whether prolonged the interval of tumor necrosis factor （TNF）-α inhibitors （TNF-i） injection could continuously improve inflammatory biomarkers and imaging changes of sacroiliac joint and spine in spondyloarthritis （SpA）.MethodsA total of 154 SpA patients were included and 95 of them received TNF-α inhibitor therapy. TNF-i used in this study included etanercept, infliximab and adalimumab. The dose of etanercept was gradually reduced from 50 mg per week to every two weeks, every three weeks and then per month. The infusion of Infliximab was reduced from 4 mg/kg at 0, 2, 6 week to every 8 weeks, every 12 weeks and then every 16 weeks. The interval of Adalimumub injection was changed from 40 mg every two weeks to 3 weeks to 4 weeks and then to two months. The levels of inflammatory parameters, bath ankylosing spondylitis disease activity index （BASDAI）, bath ankylosing spondylitis functional index （BASFI）, ankylosing spondylitis disease activity score （ASDAS）, spondyloarthritis research consortium of canada （SPARCC） scores of sacroiliac joint and fat metaplasia, bone erosion, sclerosis and ankylosis changes on magnetic resonance imaging （MRI） were investigated every 3 to 6 months. Radiograhs of spine were assessed by modified stoke ankylosing spondylitis spinal score （mSASSS） scores at baseline and 2 years. Analyses were performed by Paired t-test, Wilcoxon test, Mann-Whitney U test, Kruskal-Wallis and Chi-square test.ResultsAfter 3 months of treatment, erythrocyte sedimentation rate （ESR）, c reactive protein （CRP）, immunoglobulin A （IgA）, BASDAI, BASFI, ASDAS and SPARCC scores were significantly lower than those of the baseline [13.00（6.00, 31.00） mm/1 h vs 3.00 （2.00, 6.00） mm/1 h, Z=-5.61; 7.39（2.52, 17.90） mg/L vs 1.88（1.21,3.75） mg/L, Z=-5.57; 2.89（2.52, 17.90） g/L vs 2.27（1.60, 2.85） g/L, Z=-4.69; （2.57±1.43） vs （1.17±0.92）, t=9.81; 17.50（5.00, 27.00） vs 4.00（0, 11.00）, Z=-6.69; 2.62（2.02, 3.52） vs 1.22（0.92, 1.59）, Z=-6.96; 25.00（10.00, 37.00） vs 12.00（6.00, 20.25）, Z=-6.68; all P〈0.05]. Compared to 3-6 months, SPARCC scores were significantly reduced during 2-3 years in the TNF-i group [12.00（6.00, 20.25） vs 7.00（3.25, 14.75）, P=0.02]. There were no significant progresses in fat metaplaisa, bone erosions, sclerosis or ankylosis during the follow-up period （61%, 57%, χ2=0.07, P=1.00; 53%, 43%, χ2=0.40, P=0.75; 31%, 57%, χ2=3.02, P=0.11; 14%, 7%, χ2=0.43, P=0.66）. The mSASSS scores were not different between TNF-i group and TNF-i group after 2 years of treatment [2.50（0,8.00） vs 3.00（0,8.00）, Z=-0.30, P=0.76].ConclusionProlonged the interval of TNF-i treatment could continuously improve bone marrow edema in SpA, whereas structural damages of sacroiliac joints and spine are not deteriorated.
出处
《中华风湿病学杂志》
CSCD
北大核心
2017年第11期724-731,共8页
Chinese Journal of Rheumatology
关键词
脊柱关节炎
生物制剂减量
SPARCC评分
结构性病变
Spondyloarthritis
Tapering therapy of tumor necrosis factor -α inhibitor
AnkylosingSpondylitis Disease Activity Score score
Structural damages
