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.


Radiographic Progression Is Associated with Resolution of Systemic Inflammation in Patients with Axial Spondyloarthritis Treated with TNF Inhibitors.

Pedersen8,  Susanne Juhl, Sorensen13,  Inge Juul, Hermann4,  Kay-Geert, Garnero17,  Patrick, Johansen1,  Julia S., Madsen9,  Ole Rintek, Hansen15,  Annette

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
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, Charité University Hospital, Berlin, Germany
Dep. of Radiology, Herlev University Hospital, Copenhagen, Denmark
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 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 TNFa 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 TNFa 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 TNFa inhibitors was associated with resolution of systemic inflammation and reduction in MRI inflammation but not with baseline inflammation.

Table 1. Changes in inflammatory parameters (CRP, IL-6 and MRI) versus radiographic progression

 Radiographic progression week 0–46
 New syndesmophyte (>=1)mSASSS progression (>=1)
Changes from baseline to week 0–22No N=25Yes N=11p-valueNo N=18Yes N=18p-value
CRP decreased to <=8 mg/l11 (52)10 (48) 7 (33)14 (67) 
CRP remained >8 mg/l7 (100)0 (0)0.03†6 (86)1 (14)0.03†
CRP remained <=8 mg/l7 (87)1 (13)NS§5 (63)3 (38)NS§
IL-6 decreased to <=3.3 ng/l10 (50)10 (50) 7 (65)13 (35) 
IL-6 remained >3.3 ng/l7 (100)0 (0)0.03†7 (100)0 (0)0.006†
IL-6 remained <=3.3 ng/l8 (89)1 (11)NS§5 (55)4 (45)NS§
Change in MRI SIJ IS <07 (47)8 (53) 6 (40)9 (60) 
Change in MRI SIJ IS >=110 (91)1 (9)0.04†6 (55)5 (45)NS
MRI SIJ IS=0 at week 06 (86)1 (14)NS§5 (71)2 (29)NS
Number (%). Chi2 test and Fisher's Exact test.
†Normalization vs. persistently increased biomarker levels.
§Normalization vs. normal levels at baseline.

To cite this abstract, please use the following information:
Pedersen, Susanne Juhl, Sorensen, Inge Juul, Hermann, Kay-Geert, Garnero, Patrick, Johansen, Julia S., Madsen, Ole Rintek, et al; Radiographic Progression Is Associated with Resolution of Systemic Inflammation in Patients with Axial Spondyloarthritis Treated with TNF Inhibitors. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1953
DOI: 10.1002/art.29718

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