抗TNF治疗的397例AS患者中，CRP和脊柱外受累对 ASDAS疗效的影响

原文

译文

The Role of CRP and Peripheral Disease in Achieving ASDAS Response to Anti-TNF Therapy in 397 Patients with Ankylosing Spondylitis

 

Karen Minde Fagerli ¹, Elisabeth Lie², D.M.F.M. van der Heijde³, Marte S. Heiberg¹, Erik Rødevand⁴, Cecillie Kaufmann⁵, Knut Mikkelsen⁶, Synnøve Kalstad⁷ and Tore K. Kvien², ¹Diakonhjemmet hospital, Oslo, Norway, ²Diakonhjemmet Hospital, Oslo, Norway, ³Leiden University Medical Center, Leiden, Netherlands, ⁴Trondheim, Norway, ⁵Vestre Viken, Drammen, Norway, ⁶Lillehammer Hosp for Rheumatic Diseases, Lillehammer, Norway, ⁷Tromsø, Norway

 

Presentation Number: 531

 

Background/Purpose: BASDAI has been the most commonly used outcome measure for assessing efficacy of TNF-inhibitors (TNFi) in ankylosing spondylitis (AS). However, BASDAI is solely patient-reported. ASDAS is a recently developed composite disease activity score incorporating an inflammatory marker (CRP or ESR). It has not been well studied if ASDAS performs similarly in patients with elevated CRP vs. normal CRP and patients with swollen joints vs. patients without swollen joints.

Objective: To compare the response to TNFi according to different response criteria in patients with and without swollen joints as well as with and without elevated CRP.

Method:  Data for these analyses were extracted from the NOR-DMARD register where adult patients with inflammatory arthropathies starting a new DMARD treatment have been consecutively included and followed longitudinally with assessments at 3, 6 and 12 months and then yearly. Patients with AS starting a TNFi who had complete data for calculating ASDAS-CRP at baseline and 3 months were selected for the current analyses. Cut-point for elevated CRP was selected as 10 mg/L. The presence of a swollen joint was based on evaluation of the 28-joint count as well as feet. Selected response criteria were ASDAS clinically important improvement (Δ ≥1.1), ASDAS major improvement (Δ ≥2.0), ASAS20, ASAS40, BASDAI50, BASDAI 2-point change and BASDAI response (BASDAI50 and/or BASDAI 2-point change).

Result: 397 patients starting a TNFi were included in the analyses (70.2% males, 91.2% HLA B27 positive, mean (SD) age 42.7 (11.2) yrs, disease duration 11.8 (11.2) yrs, BASDAI 5.4 (2.1) and ASDAS 3.4 (1.1), median (IQR) CRP 9.0 (5.0-20.5) mg/L). 42.8% of patients had CRP levels ≥10 and 21.3% had at least one swollen joint. A significantly higher proportion of patients with a CRP ≥10 showed a response as compared to patients with a CRP <10 with all response criteria (table). This difference was most pronounced using ASDAS response criteria, but the % with ASDAS clinically important improvement in the patients with CRP < 10 was still in the same range as picked up with other response measures. When comparing the patients with or without swollen joints there was only a significant difference in achieving ASDAS major improvement.

Conclusion: AS patients starting a TNFi who had a baseline CRP ≥10 more frequently achieved a response compared to patients with CRP <10. These findings were seen for ASDAS responses but also for measures that do not include inflammatory markers. The response rate for ASDAS clinically important improvement was similar to responses for other measures and the findings support the use of ASDAS as a response measure also in patients with normal CRP and without swollen joints.  

 

 

抗TNF治疗的397例AS患者中，CRP和脊柱外受累对 ASDAS疗效的影响

Karen Minde Fagerli , et al. ACR 2011. Present No: 531

背景/目的:BASDAI已成为强直性脊柱炎(AS) TNF抑制剂(TNFi)治疗最常用的疗效评价指标 。然而, BASDAI 完全是的病人主观报告。ASDAS则是近年来发展起来的综合疾病活动指数，其纳入了炎性指标(CRP和ESR)。 然而，CRP升高与否或关节肿胀与否的患者中， ASDAS应用的一致性尚未达到评估。

摘要目的: 根据不同疗效标准，比较有或无肿胀关节和有或无CRP升高的患者对TNFi治疗的效果。

方法:本研究数据来自成人炎症关节病的 NOR-DMARD登记系统，连续纳入开始新DMARD治疗的患者并持续随访，并在3个月、6个月、12个月以及随后每年进行相应评估。选择开始TNFi治疗的AS患者中有完整数据可计算基线和3个月ASDAS-CRP的进行分析。CRP增高的界定值定为10mg/L。肿胀关节的有无以28关节计数为基础。所选的疗效标准为ASDAS临床重要改善(≥1.1),ASDAS显著改善(≥2.0),ASAS20,ASAS40,BASDAI50,BASDAI 2分改善和BASDAI反应(BASDAI50和/或BASDAI 2分变化)。

结果:共纳入397例开始TNFi治疗的患者 (70.2%男性,91.2% HLA B27阳性,平均(SD)年龄42.7(11.2),病程11.8(11.2)年,BASDAI 5.4(2.1), ASDAS 3.4(1.1),中位数(IQR) CRP 9.0(5.0 - -20.5) mg/L)。42.8%的患者CRP水平≥10, 21.3%的患者至少有一个肿胀关节。CRP≥10的患者所有的疗效指标有效率均显著高于CRP<10的患者 (表)。这种差异在ASDAS疗效标准中最为显著, 但CRP< 10的患者群中ASDAS临床重要改善的%与其他疗效评价在同样的范围内。当比较有无关节肿胀患者时，仅ASDAS显著改善存在明显差异 。

结论：开始TNFi治疗的AS患者，基线水平CRP≥10比CRP< 10的患者更易有效。该结果可见于ASDAS疗效指标和不包括炎症标记的评价指标。ASDAS 临床重要改善的比例与其他标准相似，结果支持ASDAS作为疗效评价指标，其在CRP正常和无肿胀关节的患者中同样有效。

Table: Percentages achieving response according to different criteria

	Overall	CRP mg/L)			Swollen joints
		≥10	<10	p-value*	Present	Absent	p-value*
ASDAS clinically important improvement	52.4	75.3	35.2	<0.001	56.1	50.2	0.38
ASDAS major improvement	26.7	44.1	13.7	<0.001	39.0	22.8	0.004
ASAS 20	61.4	61.8	43.6	<0.001	53.7	50.2	0.62
ASAS 40	36.0	44.1	30.0	0.004	40.2	34.7	0.37
BASDAI 50	43.1	50.6	37.4	0.01	43.2	40.2	0.71
BASDAI 2 points	49.4	57.6	43.2	0.005	56.1	46.9	0.17
BASDAI response	54.2	61.8	48.5	0.01	57.3	52.5	0.46

*Chi-square test.