Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


MRI Inflammation in the Sacroiliac Joints Is Associated with CTX-II and Changes in Systemic Inflammation during TNF Inhibitor Therapy.

Pedersen8,  Susanne Juhl, Sorensen13,  Inge Juul, Lambert5,  Robert, Hermann17,  Kay-Geert, Garnero18,  Patrick, Johansen1,  Julia S., Madsen9,  Ole Rintek

Dep. of Internal Medicine, Herlev Hospital, Copenhagen, Denmark
Dep. of Rheumatology, Herlev Hospital, Copenhagen, Denmark
Dep. of Rheumatology, Horsens Hospital, Denmark
Dep. of Rheumatology, Hvidovre and Glostrup Hospitals, Copenhagen, Denmark
Dep. of Rheumatology, Hvidovre and Glostrup Hospitals and DANBIO, Copenhagen, Denmark
Dep. of Rheumatology, Hvidovre Hospital, Copenhagen, Denmark
Dep. of Rheumatology, Rigshospitalet, Copenhagen, Denmark
Dep. of Rheumatology, Vejle Hospital, Denmark
Departments of Radiology, Charité University Hospital, Berlin, Germany
INSERM Unit 664, Lyon, and Cisbio Bioassays Bagnols/Cèze, France
Rheumatism Hospital, University of Southern Denmark, Graasten, Denmark
Dep. of Radiology, Aabenraa Hospital, Aabenraa, Denmark
Dep. of Radiology, Aarhus University Hospitals, Aarhus, Denmark
Dep. of Radiology, Herlev University Hospital, Copenhagen, Denmark
Dep. of Radiology, University of Alberta, Canada
Dep. of Radiology, Vejle Hospital, Vejle, Denmark
Dep. of Rheumatology, Bispebjerg Hospital, Copenhagen, Denmark
Dep. of Rheumatology, Gentofte and Herlev Hospitals, Copenhagen, Denmark
Dep. of Rheumatology, Gentofte Hospital, 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 TNFa 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 TNFa 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 mg/l (25–62) vs. 69 (46–106), p=0.03). After 22 weeks of anti-TNFa 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).

Table 1. Changes in biomarkers of inflammation (CRP and IL-6) versus change in Berlin MRI inflammation score

Changes from baseline to week 0–22SIJ Inflammation score
 Decreased N=17Unchanged/Persistent N=16p-value
CRP decreased to <=8 mg/l12 (71)5 (29) 
CRP remained >8 mg/l1 (0)7 (100)0.01†
CRP remained <=8 mg/l4 (50)4 (50)NS§
IL-6 decreased to <=3.3 ng/l15 (79)4 (21) 
IL-6 remained >3.3 ng/l1 (14)6 (86)0.005†
IL-6 remained <=3.3 ng/l1 (14)6 (86)0.005§
Number (%). Chi2 test and Fisher's Exact test.†Normalization vs. persistently increased biomarker levels.§Normalization vs. normal levels at baseline

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 TNFa inhibitors was associated with decrease in systemic inflammation.

To cite this abstract, please use the following information:
Pedersen, Susanne Juhl, Sorensen, Inge Juul, Lambert, Robert, Hermann, Kay-Geert, Garnero, Patrick, Johansen, Julia S., et al; MRI Inflammation in the Sacroiliac Joints Is Associated with CTX-II and Changes in Systemic Inflammation during TNF Inhibitor Therapy. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :134
DOI: 10.1002/art.27903

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