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[1953] - Radiographic Progression Is Associated with Resolution of Systemic Inflammation in Patients with Axial Spondyloarthritis Treated with TNFα Inhibitors.

Susanne Juhl Pedersen¹,Inge Juul Sørensen²,Kay-Geert Hermann³,Patrick Garnero⁴,Julia S Johansen⁵,Ole Rintek Madsen⁶,Annette Hansen⁷,Michael Sejer Hansen⁸,Gorm Thamsborg⁹,Lis Smedegaard Andersen¹⁰,Ole Majgaard¹¹,Anne Gitte Loft¹²,Jon Erlendsson¹³,Karsten Asmussen¹⁴,Anne Grethe Jurik¹⁵,Jakob Møller¹⁶,Maria Hasselquist¹⁶,Dorrit Mikkelsen¹⁷,Thomas Skjødt¹⁸,Mikkel Østergaard¹⁹. ¹Dep. of Rheumatology, Gentofte and Herlev Hospitals, Copenhagen, Denmark,²Dep. of Rheumatology, Hvidovre and Glostrup Hospitals and DANBIO, Copenhagen, Denmark,³Dep. of Radiology, Charité University Hospital, Berlin, Germany,⁴INSERM Unit 664, Lyon, and Cisbio Bioassays Bagnols/Cèze, France,⁵Dep. of Internal Medicine, Herlev Hospital, Copenhagen, Denmark,⁶Dep. of Rheumatology, Gentofte Hospital, Copenhagen, Denmark,⁷Dep. of Rheumatology, Rigshospitalet, Copenhagen, Denmark,⁸Dep. of Rheumatology, Herlev Hospital, Copenhagen, Denmark,⁹Dep. of Rheumatology, Glostrup Hospital, Copenhagen, Denmark,¹⁰Rheumatism Hospital, University of Southern Denmark, Graasten, Denmark,¹¹Dep. of Rheumatology, Hvidovre Hospital, Copenhagen, Denmark,¹²Dep. of Rheumatology, Vejle Hospital, Denmark,¹³Dep. of Rheumatology, Horsens Hospital, Denmark,¹⁴Dep. of Rheumatology, Bispebjerg Hospital, Copenhagen, Denmark,¹⁵Dep. of Radiology, Aarhus University Hospitals, Aarhus, Denmark,¹⁶Dep. of Radiology, Herlev University Hospital, Copenhagen, Denmark,¹⁷Dep. of Radiology, Aabenraa Hospital, Aabenraa, Denmark,¹⁸Dep. of Radiology, Vejle Hospital, Vejle, Denmark,¹⁹Dep. of Rheumatology, Hvidovre and Glostrup Hospitals, Copenhagen, Denmark

Objectives: To explore the relation between radiographic progression 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) and MRI inflammation in patients with axial spondyloarthritis (SpA) treated with TNFα inhibitor.
Methods: Thirty-six patients (27 men, 9 women; median age 40 yrs (range 21-62); disease duration 15 yrs (1-45)) initiated treatment with TNFα inhibitors (infliximab (n=28), etanercept (n=7) and adalimumab (n=1)) and were followed for 46 weeks. Radiographs were evaluated according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) at baseline and week 46. Patients developing new syndesmophytes (0 vs. ≥1) or increased in mSASSS (0 vs. ≥1 unit) were compared with those who did not, regarding biomarker levels and MRI inflammation scores of the sacroiliac joints and lumbar spine (Berlin scores) and with biomarker levels of healthy subjects.
Results: The patients increased in mSASSS from median 13 (IQR: 6-24) at baseline to 15 (6-24) (p=0.005) at week 46 (p=0.005). Eighteen (50%) patients increased in mSASSS (i.e. progressed) and 11 (30%) developed new syndesmophytes. mSASSS and biomarkers did not correlate. Compared to mSASSS non-progressors, mSASSS progressors had higher pretreatment total aggrecan (666 ng/ml (537-820) vs. 507 (401-646), p=0.007) and higher time-integrated mean concentrations of total aggrecan from baseline to week 22 (743 ng/ml (612-849) vs. 602 (446-707), p=0.02) and 46 (746 ng/ml (636-895) vs. 638 (450-735), p=0.02). Patients developing new syndesmophytes also had higher time-integrated mean concentration of total aggrecan from baseline to week 22 and 46 as compared to patients without new syndesmophytes (results like above). Development of new syndesmophytes was associated with larger percentage decreases in CRP (-90% (-96;-78) vs. -58 (-88;-25), p=0.007) and IL-6 (-81% (-93;-75) vs. -67 (-89;-16), p=0.02) and increases in osteocalcin (20% (9;36) vs. 9% (-10;25), p=0.049). Radiographic progression was associated with normalization of CRP and IL-6 at week 22 (i.e. CRP ≤8 mg/l and IL-6≤3.3 ng/l) and decrease in MRI inflammation. Radiographic non-progression was associated with persistent systemic inflammation and unchanged/increased MRI inflammation scores (Table 1).
Conclusion: Radiographic progression in patients with axial SpA during treatment with TNFα inhibitors was associated with resolution of systemic inflammation and reduction in MRI inflammation but not with baseline inflammation.

中轴型SpA患者使用TNF拮抗剂治疗后放射学进展与全身炎症消退相关

Pedersen SJ, et al. ACR 2010. Present No: 1953.

目的：探讨中轴型SpA患者接受TNF拮抗剂治疗后，放射学进展与炎症标记物（CRP、IL-6、YKL-40）、血管生成（VEGF）、软骨转换（CTX-II、MMP3、总软骨蛋白聚糖、COMP）、骨转换（CTX-I、总骨钙素）和MRI炎症的相关性。

方法：36例患者（27例男性，9例女性；平均年龄40岁；平均病程15年）使用TNF拮抗剂（英夫利昔单抗28例，依那西普7例，阿达木单抗1例）治疗46周。在基线期和第46周，采用mSASSS评分方法进行放射学评估。根据有无新发韧带骨赘或mSASSS评分升高，将患者就生物标记物水平、MRI骶髂关节和腰椎炎症评分（柏林评分）进行比较，并与健康对照者的生物标记物水平比较。

结果：患者的mSASSS从基线期平均13（IQR: 6-24）上升至第46周平均15（6-24）（p=0.005）。18例（50%）患者mSASSS升高（即进展），11例（30%）出现新的韧带骨赘。mSASSS与生物标记物没有相关性。与mSASSS无进展者相比，mSASSS进展者治疗前总软骨蛋白聚糖水平更高（666 ng/ml (537-820) vs. 507 (401-646), p=0.007），从基线期到第22周时间积分的总软骨蛋白聚糖平均浓度更高（746 ng/ml (636-895) vs. 638 (450-735), p=0.02）。与无新发韧带骨赘的患者相比，新发韧带骨赘的患者从基线期到第22周和第46周时间积分的总软骨蛋白聚糖平均浓度更高（结果与前相似）。新发韧带骨赘与CRP（-90% (-96;-78) vs. -58 (-88;-25), p=0.007）和IL-6（-81% (-93;-75) vs. -67 (-89;-16), p=0.02）降低百分比更大相关，与骨钙素升高百分比更大相关（20% (9;36) vs. 9% (-10;25), p=0.049）。放射学进展与第22周CRP和IL-6正常（即CRP ≤8 mg/l，IL-6≤3.3 ng/l）、MRI炎症减轻相关。无放射学进展与全身炎症持续、MRI炎症评分无变化/上升相关（表1）。

结论：接受抗TNF治疗的中轴型SpA患者放射学进展与全身炎症消退、MRI炎症减轻相关，与基线期炎症无关。

表1. 炎性参数(CRP, IL-6和MRI)与放射学进展的变化值

例数(%)。卡方检验和Fisher精确检验。

†: 生物标记物水平降低者与持续升高者相比。§:基线水平降低者与正常者相比。