Rheumatology Advance Access originally published online on August 9, 2006
Rheumatology 2007 46(3):446-453; doi:10.1093/rheumatology/kel262
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Autoantibodies, metalloproteinases and bone markers in rheumatoid arthritis patients are unable to predict their responses to infliximab
1Rheumatology Department, Rouen University Hospital, 2Inserm U519, IFR 23, Faculté de Médecine, 3Immunology Department, Rouen University Hospital, Rouen, 4Laboratory of Bone Biology, Amiens University Hospital, Amiens, 5Biochemical Department and 6Biostatistics Department, Rouen University Hospital, Rouen, France.
Correspondence to: Dr T. Lequerré, Department of Rheumatology, Rouen University Hospital, 76031 Rouen Cedex, France. E-mail: thierry.lequerre{at}univ-rouen.fr
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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,
-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-
B ligand, cartilage oligomeric matrix protein. Each parameter's predictive value of the response to infliximab was analysed using Fisher's exact, MannWhitney 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.
KEY WORDS: Rheumatoid arthritis, Infliximab, Predictive factors of response, TNF-
blocking agent, Prognosis
Submitted 29 October 2005;
revised version accepted 27 June 2006.
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