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[134] - MRI Inflammation in the Sacroiliac Joints Is Associated with CTX-II and Changes in Systemic Inflammation during TNFα Inhibitor Therapy.

Susanne Juhl Pedersen¹,Inge Juul Sørensen²,Robert Lambert³,Kay-Geert Hermann⁴,Patrick Garnero⁵,Julia S Johansen⁶,Ole Rintek Madsen⁷,Annette Hansen⁸,Michael Sejer Hansen⁹,Gorm Thamsborg¹⁰,Lis Smedegaard Andersen¹¹,Ole Majgaard¹²,Anne Gitte Loft¹³,Jon Erlendsson¹⁴,Karsten Asmussen¹⁵,Anne Grethe Jurik¹⁶,Jakob Møller¹⁷,Maria Hasselquist¹⁷,Dorrit Mikkelsen¹⁸,Thomas Skjødt¹⁹,Mikkel Østergaard²⁰. ¹Dep. of Rheumatology, Gentofte and Herlev Hospitals, Copenhagen, Denmark,²Dep. of Rheumatology, Hvidovre and Glostrup Hospitals and DANBIO, Copenhagen, Denmark,³Dep. of Radiology, University of Alberta, Canada,⁴Departments of Radiology, Charité University Hospital, Berlin, Germany,⁵INSERM Unit 664, Lyon, and Cisbio Bioassays Bagnols/Cèze, France,⁶Dep. of Internal Medicine, Herlev Hospital, Copenhagen, Denmark,⁷Dep. of Rheumatology, Gentofte Hospital, Copenhagen, Denmark,⁸Dep. of Rheumatology, Rigshospitalet, Copenhagen, Denmark,⁹Dep. of Rheumatology, Herlev Hospital, Copenhagen, Denmark,¹⁰Dep. of Rheumatology, Glostrup Hospital, Copenhagen, Denmark,¹¹Rheumatism Hospital, University of Southern Denmark, Graasten, Denmark,¹²Dep. of Rheumatology, Hvidovre Hospital, Copenhagen, Denmark,¹³Dep. of Rheumatology, Vejle Hospital, Denmark,¹⁴Dep. of Rheumatology, Horsens Hospital, Denmark,¹⁵Dep. of Rheumatology, Bispebjerg Hospital, Copenhagen, Denmark,¹⁶Dep. of Radiology, Aarhus University Hospitals, Aarhus, Denmark,¹⁷Dep. of Radiology, Herlev University Hospital, Copenhagen, Denmark,¹⁸Dep. of Radiology, Aabenraa Hospital, Aabenraa, Denmark,¹⁹Dep. of Radiology, Vejle Hospital, Vejle, Denmark,²⁰Dep. of Rheumatology, Hvidovre and Glostrup Hospitals, Copenhagen, Denmark

Objectives: To investigate the relation between inflammation in the sacroiliac joints (SIJ) on magnetic resonance imaging (MRI) and biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), YKL-40), angiogenesis (vascular endothelial growth factor (VEGF)), cartilage turnover (CTX-II, matrix metalloproteinase 3 (MMP3), total aggrecan, cartilage oligomeric matrix protein (COMP)) and bone turnover (CTX-I, total osteocalcin) in patients with axial spondyloarthritis (SpA) treated with TNFα inhibitors.
Methods: Forty-three patients (34 men, 9 women; median age 40 yrs (range 21-62); disease duration 14 yrs (1-45)) initiated treatment with TNFα inhibitors (infliximab (n=31), etanercept (n=9) and adalimumab (n=3)) and were followed for 46 weeks. MR images were evaluated according to the Berlin SIJ inflammation scoring method at baseline, week 22 and 46. Biomarker levels of the patients were compared to these scores and biomarker levels of healthy subjects.
Results: The patients had a pretreatment MRI SIJ score of median 5 (range: 0-23) and SIJ inflammation was seen in 33 (77%) patients. The SIJ scores correlated with CTX-II (rho=0.57, p<0.0001) and COMP (inversely, -0.36, p=0.02), whereas no correlations were seen with the other 8 biomarkers. Compared to patients without pretreatment SIJ inflammation, patients with SIJ inflammation (MRI score ≥1) had higher baseline urine CTX-II levels (median 490 ng/mmol (IQR: 396-766) vs. 245 (128-345), p=0.003), and higher time-integrated mean concentrations of CTX-II from baseline to week 22 (461 ng/mmol (313-665) vs. 311 (185-404), p=0.04) and to week 46 (418 ng/mmol (286-610) vs. 214 (175-306) p=0.009) and lower YKL-40 from baseline to week 46 (41 µg/l (25-62) vs. 69 (46-106), p=0.03). After 22 weeks of anti-TNFα therapy 17 (52%) patients with SIJ inflammation on baseline MRI decreased in score, whereas 16 (48%) patients were unchanged or increased in score. A decrease in SIJ scores after 22 weeks was associated with larger percentage decreases in CRP (-84% (-94;-67) vs. -45% (-65;-18), p=0.008) and IL-6 (-76% (-88;-73) vs. -43% (-84;15), p=0.03) but not with any other biomarker as compared to unchanged/increased SIJ score. CRP and IL-6 frequently normalized after 22 weeks (i.e. CRP ≤8 mg/l and IL-6 ≤3.3 ng/l) in patients with a decrease in SIJ score as compared to patients with unchanged/increased SIJ score (Table 1).
Conclusion: Inflammation in SIJ on baseline MRI was associated with higher urine levels of the cartilage degradation biomarker CTX-II. Decrease in MRI inflammation during treatment with TNFα inhibitors was associated with decrease in systemic inflammation.

MRI骶髂关节炎症与CTX-II变化以及TNF拮抗剂治疗过程中全身炎症改变相关

Pedersen SJ, et al. ACR 2010. Present No: 134.

目的：观察MRI的骶髂关节（SIJ）炎症与接受TNF拮抗剂治疗的中轴型脊柱关节炎患者的炎症标记物（CRP、IL-6、YKL-40）、血管生成标记物（血管内皮生长因子[VEGF]）、软骨转换标记物（CTX-II、基质金属蛋白酶3[MMP3]、总软骨蛋白聚糖、软骨寡聚基质蛋白[COMP]）、骨转换标记物（CTX-I、总骨钙素）的相关性。

方法：43例患者（34名男性，9名女性，平均年龄40岁[21-62岁]，平均病程14年[1-45年]）接受TNF拮抗剂治疗（英夫利昔单抗[n=31]、依那西普[n=9]、阿达木单抗[n=3]），随访46周。在基线期、第22周和第46周行MRI检查，根据柏林SIJ炎症评分方法进行评估。比较患者和健康对照者的生物标记物水平、MRI评分健康对照者的生物标记物水平进行比较。

结果：治疗前患者的MRI SIJ平均评分为5（0-23），33例患者（77%）可见SIJ炎症。SIJ评分与CTX-II呈正相关（rho=0.57, p<0.0001），与COMP呈负相关 (-0.36, p=0.02)，而与其他8种生物标记物无相关性。与治疗前无SIJ炎症的患者相比，有SIJ炎症的患者（MRI评分≥1）在基线期尿CTX-II水平更高（平均490 ng/mmol [IQR: 396-766] vs. 245 [128-345], p=0.003），从基线期到第22周的CTX-II时间积分平均浓度更高（461 ng/mmol [313-665] vs. 311[185-404], p=0.04），从基线期到第46周的CTX-II时间积分平均浓度更高（418 ng/mmol [286-610] vs. 214 [175-306], p=0.009），从基线期到第46周的YKL-40更低（41 µg/l [25-62] vs. 69 [46-106], p=0.03）。在TNF拮抗剂治疗22周后，17例（52%）基线期MRI有SIJ炎症的患者评分降低，而另外16例（48%）患者评分没有变化或者升高。22周后SIJ评分降低的患者与SIJ评分没有变化或升高的患者相比，CRP（-84% [-94;-67] vs. -45% [-65;-18], p=0.008）和IL-6（-76% [-88;-73] vs. -43% [-84;15], p=0.03）降低百分比更大。在SIJ评分降低的患者中，CRP和IL-6在22周后多降至正常水平（即CRP ≤8 mg/l和IL-6 ≤3.3 ng/l）。

结论：基线期MRI SIJ炎症与尿中软骨降解生物标记物CTX-II水平较高相关。TNF拮抗剂治疗后MRI炎症降低与全身炎症降低相关。