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
Department of Medicine, Division of Rheumatology
Medical Subject Headings
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
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.
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Citation: J Rheumatol. 2009 Jul;36(7):1371-9. doi: 10.3899/jrheum.080755. Epub 2009 Jun 1. Link to article on publisher's site
Visvanathan, Sudha; Wagner, Carrie; Rojas, Jeannie; Kay, Jonathan; Dasgupta, Bhaskar; Matteson, Eric L.; Mack, Michael; Baker, Daniel G.; and Rahman, Mahboob U., "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" (2009). Rheumatology Publications and Presentations. 90.