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Abstract Number: 538

Association Between Biomarkers (Metalloproteinase-3, Dikkopf-1 and Sclerostin) with Disease Activity and Prediction of Anti-TNFá Therapy Response in Patients with Ankylosing Spondylitis

Victoria Navarro-Compán1, Rafael Ariza2, Rufino Mondéjar-García3, Virginia Moreira-Navarrete4, Enrique Melguizo-Madrid3, Blanca Hernández-Cruz4, Concepción González-Rodríguez3 and Federico Navarro-Sarabia5, 1Leiden University Medical Center, Leiden, Netherlands, 2Rheumatology, University Hospital Virgen Macarena.Sevilla, Sevilla, Spain, 3Biochemistry, University Hospital Virgen Macarena, Sevilla, Spain, 4Rheumatology, University Hospital Virgen Macarena, Sevilla, Spain, 5Rheumatology, Hospital Virgen Macarena, Serv. de Reumatología, Sevilla, Spain

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: Ankylosing spondylitis (AS), anti-TNF therapy and biomarkers

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Session Information

Session Title: Spondylarthropathies and Psoriatic Arthritis: Clinical Aspects and Treatment

Session Type: Abstract Submissions (ACR)

Background/Purpose: Better objectives measures for evaluating disease activity and anti-TNFα response in patients with ankylosing spondylitis (AS) are needed. MMP-3 seems to be the most promising biomarker but published data are not conclusive. The aim of this study was to investigate the association between serum biomarkers (MMP-3, DKK-1 and sclerostin) levels with disease activity parameters and to evaluate if these biomarkers are useful to predict anti-TNFα response in patients with AS.


Methods: From November 2010 to July 2011, consecutive patients with AS (New York criteria) who initiated anti-TNFα therapy in a University hospital were included. Before and after 3 months of therapy, disease activity was measured using BASDAI, ASDAScrp, CRP, patient’s VAS of pain and patient’s and physician’s VAS of global disease activity (GDA). Blood samples for determination of serum levels of biomarkers by enzyme immunoassay were also collected at both visits.
Spearman correlation test was used to evaluate association between biomarkers and disease activity parameters. Biomarkers change was compared in responders versus non-responders, based on BASDAI50 and ASDAS response using Mann-Whitney U test. Accuracy to predict response (ROC analysis) was performed.


Results:
Twenty AS patients were included; 80% received adalimumab and 20% received etanercept. Median (IQR) age and disease duration were 42.4 (31-49) years and 6.8 (3-10) years, respectively; 86% were men, and 83% HLA-B27 positive. Inverse correlation between patient’s VAS pain and MMP-3 at baseline was the only significant observed correlation between investigated biomarkers and disease activity parameters (table 1).  MMP-3 levels decreased only in patients who responded to anti-TNF therapy but increased in patients who did not response (table 2). Baseline biomarkers serum levels (including CRP) for both groups were similar except for MMP-3 (122.9 vs 58.9; p<0.05). The area under the curve for MMP-3 to predict BASDAI50 and ASDAS response was 0.73 and 0.78, respectively. The best cut-off was established for levels higher than 59.5, with sensibility of 79-85% and specificity of 50-57%.

 

Conclusion: No correlation was observed between serum levels of MMP-3, DKK-1 and sclerostin and disease activity parameters in patients with AS. Serum levels of MMP-3 may be useful to predict response to anti-TNFα therapy in patients with AS.

 

 

 

 

 

 

 

 

 

 

 

Table 1: Correlation between serum levels of biomarkers with disease activity parameters.

 

 

BASDAI

ASDAScrp

Pt GDA

Pt VAS pain

Phy GDA

CRP

At baseline

 

 

 

 

 

 

   MMP-3

-0.318

-0.086     

-0.334

 -0.477*

-0.551

0.222

   DKK-1

-0.017

-0.045

 0.003

 0.149

 0.234

0.107

   SOST

-0.096

-0.039

-0.074

 0.066

-0.154

0.002

   CRP

-0.288

   0.577**

 0.122

 0.039

 0.032

1.000

After 3 months

 

 

 

 

 

 

   MMP-3

-0.135

-0.144

-0.169

-0.154

-0.156

-0.024

   DKK-1

-0.007

 0.168

 0.155

 0.179

 0.270

 0.296

   SOST

-0.006

 0.114

 0.306

 0.166

 0.427

 0.172

   CRP

 0.003

   0.457*

 0.177

 0.173

 0.266

 1.000

              * p<0.05 ** p<0.01

 

 

 

Table 2: Change in serum levels of MMP-3, DKK-1, sclerostin and CRP after 3 months of anti-TNFα therapy based on the clinical response.

 

 

Responders

N=13 (65%)

Non-responders

N=7 (35%)

 

Baseline

3 months

p

Baseline

3 months

p

MMP-3 (ng/dl)

122.2

64.1

0.01

58.9

75.5

0.6

DKK-1 (ng/dl)

6.9

8.1

0.6

7.3

6.7

0.6

SOST (pmol/dl)

23.6

23.4

0.9

18.1

21.3

0.2

CRP    (mg/l)

16.3

4.0

0.002

8.3

5.3

0.3

 


Disclosure:

V. Navarro-Compán,
None;

R. Ariza,
None;

R. Mondéjar-García,
None;

V. Moreira-Navarrete,
None;

E. Melguizo-Madrid,
None;

B. Hernández-Cruz,
None;

C. González-Rodríguez,
None;

F. Navarro-Sarabia,
None.

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