RESEARCH - E-selectin, IL-18, SSA, and MMP-9 are are associated with clinical response to golimumab plus MTX in patients with active RA

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J Rheumatol. 2009 Jun 1.

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.

Visvanathan S, Wagner C, Rojas J, Kay J, Dasgupta B, Matteson EL, Mack

M, Baker DG, Rahman MU.

From Centocor Research and Development, Inc., Malvern, Pennsylvania;

Rheumatology Unit, Massachusetts General Hospital, Boston,

Massachusetts, USA; Department of Rheumatology, Southend University

Hospital, Westcliff, Essex, United Kingdom; Department of

Rheumatology, Mayo Clinic College of Medicine, Rochester, Minnesota;

and University of Pennsylvania Medical School, Philadelphia,

Pennsylvania, USA.

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, Eselectin, 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.

PMID: 19487269

http://www.ncbi.nlm.nih.gov/pubmed/19487269

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