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Rheumatology Advance Access published online on August 9, 2006
Rheumatology, doi:10.1093/rheumatology/kel262
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received October 29, 2005
Accepted June 27, 2006

Original Papers

Autoantibodies, metalloproteinases and bone markers in rheumatoid arthritis patients are unable to predict their responses to infliximab

T. Lequerré 1 *, F. Jouen 2, M. Brazier 3, S. Clayssens 4, N. Klemmer 5, J.-F. Ménard 6, O. Mejjad 5, A. Daragon 1, F. Tron 7, X. Le Loët 1, and O. Vittecoq 1

1 Rheumatology Department, Rouen University Hospital, Rouen, France; Inserm U519, IFR 23, Faculté de Médecine, Rouen, France
2 Immunology Department, Rouen University Hospital, Rouen, France
3 Laboratory of Bone Biology, Amiens University Hospital, Amiens, France
4 Biochemical Department, Rouen University Hospital, Rouen, France
5 Rheumatology Department, Rouen University Hospital, Rouen, France
6 Biostatistics Department, Rouen University Hospital, Rouen, France
7 Inserm U519, IFR 23, Faculté de Médecine, Rouen, France; Immunology Department, Rouen University Hospital, Rouen, France

* To whom correspondence should be addressed.
T. Lequerré, E-mail: thierry.lequerre{at}univ-rouen.fr


  Abstract

Objectives. To identify biochemical, immunological and bone markers as predictors of rheumatoid arthritis (RA) patients’ responses to infliximab.

Methods. A total of 76 patients with active RA (American College of Rheumatology criteria), refractory to disease-modifying anti-rheumatic drugs, including methotrexate, received infliximab (3 mg/kg) infusions at weeks 0, 2, 6, and then every 8 weeks in combination with methotrexate or leflunomide. At week 14, infliximab efficacy was evaluated using disease activity score (DAS)28. A serum sample, collected just before starting infliximab, was tested by ELISA (unless stated otherwise) for the following immunological markers: rheumatoid factor by agglutination and ELISA (IgA, IgG and IgM isotypes); anti-cyclic citrullinated protein; autoantibodies recognizing calpastatin domain I and its 27 C-terminal fragment, glucose-6-phosphate isomerase, {alpha}-enolase; anti-keratin and anti-perinuclear factor antibodies (immunofluorescence); biochemical markers: C-reactive protein (nephelometry), metalloproteinase-1 and -3, tissue inhibitors of metalloproteinases-1 and -2, antioxidants (vitamins A and E; selenium); bone resorption markers: pyridinoline, deoxypyridinoline, osteoprotegerin, soluble receptor activator of nuclear factor-{kappa}B ligand, cartilage oligomeric matrix protein. Each parameter's predictive value of the response to infliximab was analysed using Fisher's exact, Mann-Whitney and chi-square tests. Hierarchical clustering was performed with The Institute for Genomic Research (TIGR) multiple experiment viewer software.

Results. Good, moderate and non-responder rates were 6.5, 61.8 and 31.5%, respectively. No significant difference was observed between responders and non-responders, regardless of the serum parameters considered. Analysis of dichotomous or continuous variables failed to identify markers predictive of a good or poor response to infliximab.

Conclusion. The search for soluble markers in RA patients’ sera likely to predict response to infliximab because of their involvement in RA pathogenesis seems disappointing. However, because of the limited power to detect smaller differences in biomarkers, the present study is a preliminary exploratory analysis.

Keywords: Rheumatoid arthritis; Infliximab; Predictive factors of response; TNF-{alpha} blocking agent; Prognosis.
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