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    E-selectin, interleukin 18, serum amyloid a, and matrix metalloproteinase 9 are associated with clinical response to golimumab plus methotrexate in patients with active rheumatoid arthritis despite methotrexate therapy

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    Authors
    Visvanathan, Sudha
    Wagner, Carrie
    Rojas, Jeannie
    Kay, Jonathan
    Dasgupta, Bhaskar
    Matteson, Eric L.
    Mack, Michael
    Baker, Daniel G.
    Rahman, Mahboob U.
    UMass Chan Affiliations
    Department of Medicine, Division of Rheumatology
    Document Type
    Journal Article
    Publication Date
    2009-07-01
    Keywords
    Adult
    Aged
    Antibodies, Monoclonal
    Antirheumatic Agents
    Arthritis, Rheumatoid
    Biological Markers
    C-Reactive Protein
    Dose-Response Relationship, Drug
    Double-Blind Method
    Drug Synergism
    Drug Therapy, Combination
    E-Selectin
    Female
    Humans
    Injections, Subcutaneous
    Interleukin-18
    Male
    Matrix Metalloproteinase 9
    Methotrexate
    Middle Aged
    Serum Amyloid A Protein
    Tissue Inhibitor of Metalloproteinase-1
    Musculoskeletal Diseases
    Rheumatology
    Skin and Connective Tissue Diseases
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    Link to Full Text
    http://dx.doi.org/10.3899/jrheum.080755
    Abstract
    OBJECTIVE: To assess the effect of golimumab (human monoclonal antibody to tumor necrosis factor-alpha) plus methotrexate (MTX) on selected inflammatory biomarkers, and to determine if these effects predict clinical response in rheumatoid arthritis (RA). METHODS: Sera from adults with active RA despite MTX therapy, who received subcutaneous injections of placebo + MTX (MTX alone, n = 34) or golimumab 50 or 100 mg every 2 or 4 weeks + MTX (n = 137), were analyzed for levels of C-reactive protein (CRP), serum amyloid A (SAA), interleukin 18 (IL-18), E-selectin, matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1). RESULTS: Golimumab + MTX treatment significantly decreased serum CRP, SAA, IL-18, E-selectin, TIMP-1, and MMP-9 levels (median percent changes of -4.1% to -74.3% across treatment groups) versus MTX alone (-5.8% to 9.7%) when first measured at Week 4; decreases were sustained through Week 16. Larger magnitudes of decrease in all biomarkers were observed for clinical responders versus nonresponders. For golimumab + MTX, regression analyses including all biomarkers and select clinical measures showed that reductions in levels of several markers (SAA, E-selectin, MMP-9) as early as Week 4 correlated significantly with improvement in swollen joint count (SJC) at Week 16, as did reductions in E-selectin with improvement in tender joint count at Week 16. After accounting for the biomarkers, however, treatment group was no longer significant for SJC. CONCLUSION: Significant decreases in several inflammatory biomarkers were associated with golimumab + MTX therapy. Decreases in serum levels of SAA, E-selectin, and MMP-9 at Week 4 may be useful in predicting clinical response at Week 16.
    Source
    J Rheumatol. 2009 Jul;36(7):1371-9. doi: 10.3899/jrheum.080755. Epub 2009 Jun 1. Link to article on publisher's site
    DOI
    10.3899/jrheum.080755
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/48765
    PubMed ID
    19487269
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.3899/jrheum.080755
    Scopus Count
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