背景

TNF-抑制剂可显著改善脊柱关节炎患者的疾病活动状况，然而延长TNF-抑制剂间隔对MRI变化的影响仍然没有答案。

目的

本研究的目的是探究延长TNF-抑制剂的注射间隔是否可以使脊柱关节炎患者保持较低的疾病活动状态，并改善骶髂关节的影像学变化。

方法

本研究共纳入98例脊柱关节炎患者，其中有67例患者接受了TNF-抑制剂治疗，伴随使用或不使用传统抗风湿药(DMARDs)。TNF-抑制剂包含依那西普、英夫利昔单抗、阿达木单抗。全剂量治疗被定义为患者每周注射50 mg依那西普，在第0周、2周、6周注射4 mg/kg英夫利昔单抗，每两周注射40 mg阿达木单抗。依那西普的注射剂量逐渐减少到每两周注射50 mg，每三周注射50 mg，每个月注射50 mg。英夫利昔单抗的注射剂量以每8周、每12周和每16周减少一次。阿达木单抗的注射间隔从每3周一次变到每4周一次、然后变成每两个月注射一次。在前三个月全剂量注射后，每3-6个月评估接受TNF-抑制剂治疗的患者。根据包含红细胞沉降率(ESR)、C型反应性蛋白(CRP)、IgA水平在内的实验室检测，疾病活动性指数(BASDAI)、强直性脊柱炎功能指数(BASFI)、疾病活动性得分(ASDAS)结果以及骶髂关节SPARCC得分等情况，逐渐延长TNF-抑制剂治疗间隔。在基线值、4-6个月、1-2年比较核磁共振成像(MRI)的脂肪转化、骨质侵蚀、硬化、强直性变化情况。

结果

治疗3个月后，炎症指标、疾病活动性指数(BASDAI)、强直性脊柱炎功能指数(BASFI)、疾病活动性得分(ASDAS)结果以及骶髂关节SPARCC得分明显低于基线值(P<0.05)。治疗4-6个月后，红细胞沉降率(ESR)、C型反应性蛋白(CRP)、IgA水平明显比以前低 (8 (3,25) vs. 2 (1,3) mm/h， 4.97 (1.83,14.5) vs. 1.71 (1.24,2.82) mg/l，2.96±1.34vs.2.20±1.01mg/l，见表1，P< 0.01)。与基线值相比，在TNF-抑制剂治疗组中观察到疾病活动性指数(BASDAI)、强直性脊柱炎功能指数(BASFI)评分显著降低。TNF-抑制剂治疗组的骶髂关节SPARCC得分也显著下降(图1，P<0.01)。随访期间脂肪转化、骨质侵蚀、硬化、强直性变化无显著变化(P>0.05))。尽管非TNF-抑制剂治疗组的炎症指标和临床评价均无明显改善，但骶髂关节SPARCC得分在4-6个月以及1-2年显著降低(P<0.05)。

图1 TNF-抑制剂治疗组和非TNF-抑制剂治疗组的骶髂关节SPARCC得分变化

表1治疗前后红细胞沉降率(ESR)、C型反应性蛋白(CRP)、IgA水平的变化

结论

TNF-抑制剂可降低临床和成像炎症程度。延长TNF-抑制剂治疗间隔可以维持低水平的疾病活动，改善骨髓水肿，而脂肪转化、骨质侵蚀、硬化、强直性变化并无加剧。

原 文

Background:TNF-inhibitors could significantly improve disease activity of SpA patients, however, there is still no answer to the effect of prolonged the interval of TNF-inhibitors on MRI changes.

Objectives:The aim of the study was to investigate whether prolonged the interval of TNF-inhibitor injection could maintain SpA at low disease activity and improve imaging changes of sacroiliac joint.

Methods:A total of 98 SpA patients were included and 67 of them received TNF-i with or without conventional DMARDs.TNF-i included Etanercept, Infliximab and Adalimumab. The full dosage treatment was defined as patients received Etanercept 50 mg per week, Infliximab 4 mg/kg at 0, 2, 6 week and Adalimumab 40 mg every two weeks.The dose of Etanercept was gradually reduced to 50 mg every two weeks, 50 mg every three weeks and then 50 mg per month.The infusion of Infliximab was reduced to every 8 weeks, every 12 weeks and then every 16 weeks. The interval of Adalimumub injection was changed from 3 weeks to 4 weeks and then to two months. After full dose treatment in the first 3 months, patients who administrated TNF-i were evaluated every 3–6 months. According to laboratory tests including ESR, CRP and IgA levels, BASDAI, BASFI, ASDAS results and sacroiliac joint SPARCC scores, the interval of TNF-i treatment was prolonged gradually. Fat metaplasia, bone erosion, sclerosis and ankylosis changes on MRI were compared between baseline, 4–6 months and 1–2 years.

Results:After 3 months of treatment, inflammatory indexes, BASDI, BASFI, ASDAS and SPARCC scores were significantly lower than baseline (P<0.05). After 4–6 months of treatment, ESR, CRP and IgA levels were greatly lower than before(8 (3,25) vs. 2 (1,3) mm/h, 4.97 (1.83,14.5) vs. 1.71 (1.24,2.82) mg/l, 2.96±1.34 vs. 2.20±1.01mg/l, Table 1, P<0.01).Compared to baseline, significant reduction of BASDAI and BASFI score was observed in TNF-inhibitor group. The SPARCC scores in TNF-i group also decreased significantly (Figure1, P<0.01).There was no significant progress in fat metaplaisa, bone erosions, sclerosis and ankylosis during the follow-up period (P>0.05). Even though the inflammatory indexes and clinical evaluation of non-TNF-i group did not improved remarkably, SPARCC score were significantly reduced at 4–6 months and 1–2 years (P<0.05).

Conclusions:TNF-i could reduce clinical and imaging inflammatory degree.Prolonged the interval of TNF-i treatment could maintain low disease activity and improve bone marrow edema, whereas fat metaplasia, bone erosion, sclerosis and ankylosis were not exacerbated.

转自：强直性脊柱炎在线

来源：赛金风湿汇