Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Serum Markers Associated with Structural Damage in Methotrexate Nave Rheumatoid Arthritis Patients Treated with MTX in Combination with Placebo or Golimumab, a Human Anti-TNFa Monoclonal Antibody.

Wagner2,  Carrie, Chen1,  Dion, Fan1,  Hongtao, Visvanathan5,  Sudha, Hsia3,  Elizabeth C., Emery4,  Paul, Fleischmann6,  Roy M.

Centocor Research and Development, Inc.
Centocor Research and Development, Inc., Malvern, PA
Centocor Research and Development, Inc./Univ. of Pennsylvania School of Medicine, Malvern, PA
Chapel Allerton Hospital, Leeds, United Kingdom
Hoffmann La Roche
University of Texas SW Medical Center, Dallas, TX

Purpose:

Little is known about biomarkers that are correlated with structural damage endpoints in rheumatoid arthritis (RA). The purpose of this study is to evaluate whether there are serum markers associated with structural damage in MTX naïve RA patients treated with MTX in combination with either placebo (PBO) or an anti-TNF antibody, golimumab (GLM).

Methods:

In the GO-BEFORE study, 637 patients were randomly assigned in a 1:1:1:1 ratio to receive placebo (PBO) + methotrexate (MTX), GLM 100 mg+ PBO, GLM 50 mg + MTX, or GLM 100 mg + MTX. Sera were collected at wks 0, 4 and 24 from a subset of approximately 100 patients for testing select markers of inflammation and bone/cartilage metabolism and protein profiling using multi-analyte profiles (Rules Based Medicine). The baseline, absolute change and percent change from baseline to wk 4 in these markers were compared between the PBO+MTX and the combined GLM group [GLM+MTX (50 mg + 100 mg) and GLM+PBO groups] against changes in van der Heijde modified Sharp (vdh-S) score, erosion score and joint space narrowing score at wks 28 and 52 using Spearman's correlations. Significant biomarker correlations with efficacy in the GLM group relative to the PBO treatment group were evaluated using Fisher Z-transformation test.

Results:

Biomarker correlations with structural damage endpoints were predominantly observed for only the PBO+MTX treatment group and very few correlations were observed with GLM treatment. With PBO+MTX treatment, only IL-1ra was observed to be repeatedly correlated with the structural damage endpoints at wks 28 and 52. However, there were a number of more consistently observed structural damage correlations in the PBO+MTX treatment group using either absolute change from baseline or percent change from baseline in biomarker levels. Absolute change or percent change from baseline markers that were repeatedly correlated with changes in structural damage endpoints at wks 28 and/or 52 included CD-40 ligand (CD40-L) and epidermal growth factor (EGF). There were repeated, but less frequent structural damage correlations with change or percent change in matrix metalloproteinase 3, MIP-1b and Col 2–3/4C long neoepitope. The only biomarker that was repeatedly correlated with structural damage endpoints in the GLM treatment group was IL-1ra.

Conclusions:

Biomarker correlations with structural damage endpoints were predominantly observed in the PBO+MTX treatment group, but rarely in the GLM+MTX treatment group, likely reflecting the reduced structural damage observed following anti-TNF treatment. Change and percent change from baseline to wk 4 in levels of certain markers were repeatedly associated with structural damage endpoints at wks 28 or 52 in the PBO+MTX treatment. Markers that were repeatedly associated with structural damage measures at wks 28 and/or 52 included EGF and CD40-L. CD40-L has been reported to regulate osteoclastogenesis and EGF has been implicated in bone remodeling. Additional studies are needed to confirm whether these markers would be similarly correlated with structural damage measures in MTX-refractory patients.

To cite this abstract, please use the following information:
Wagner, Carrie, Chen, Dion, Fan, Hongtao, Visvanathan, Sudha, Hsia, Elizabeth C., Emery, Paul, et al; Serum Markers Associated with Structural Damage in Methotrexate Nave Rheumatoid Arthritis Patients Treated with MTX in Combination with Placebo or Golimumab, a Human Anti-TNFa Monoclonal Antibody. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1127
DOI: 10.1002/art.28894

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