Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


Golimumab and Cardiovascular Disease in Inflammatory Arthritides

Bathon1,  J., Wasko2,  M. C., Hsia3,  E. C., Kirkham4,  B., Fleischmann5,  Roy, Genovese6,  M.C., Matteson7,  E. L.

Johns Hopkins Univ Sch of Med, Baltimore, MD,
Univ of Pittsburgh Med Ctr, Pittsburgh, PA,
Centocor R&D, Inc/U of Penn School of Med, Malvern, PA,
Guy's and St. Thomas' Hosp. London, England,
Metroplex Clinical Research Center, Dallas, TX,
Stanford U, Palo Alto, CA,
Mayo Clinic, Rochester, MN,
Centocor R&D, Inc, Malvern, PA

Purpose:

To assess the effect of golimumab (GLM) +/- MTX on serum lipid profile and inflammatory markers associated with cardiovascular disease (CVD), and on cardiovascular (CV) events.

Methods:

Serum lipids and inflammatory CV markers (eg. hsCRP, VEGF, ICAM-1 SAA, fibrinogen, IL-6) were assessed in 2 phase 3 GLM trials in pts with rheumatoid (RA): MTX-naïve (GO-BEFORE); MTX inadequate responders (IR) (GO-FORWARD). Changes from baseline (BL) to wk14 or 24 were compared between PBO+MTX (N=293) and combined GLM 50 and 100 mg + MTX (N=496) groups (grps). CV events (not adjudicated) from these & another phase 3 trial in anti-TNF experienced RA pts (GO-AFTER; N=461) were summarized.

Results:

The changes in lipid profile & a CV inflammatory marker are shown in the table. In the GO-FORWARD study, total cholesterol (TC), HDL and LDL levels all increased in the GLM+MTX compared to PBO+MTX grp whereas atherogenic ratios (TC/HDL, LDL/HDL, ApoB1/A1) were not substantially changed. Favorable changes in the LDL subfraction (increase in large and decrease in small LDL) were seen in GLM groups. In the GO-BEFORE study (with MTX-naïve pts), similar changes were seen in both the MTX and GLM groups. Most inflammatory CV markers improved significantly with GLM+MTX compared to PBO+MTX in both studies (1 shown in Table as representative data). During the PBO-controlled period, 7 of 449 pts (1.6%) in the PBO+/-MTX & 10 of 1088 pts (1%) (p=0.275) in the GLM+/-MTX grps had CV events. Through June 2, 2008 (all pts had completed >=1 yr), CV events per 100 pt-yrs (95% CI) were 2.72 (1.09, 5.6) for PBO+/-MTX & 0.8 (0.45, 1.32) for GLM+/-MTX grps (p=0.35).

Table. Data are median value or median % change.

 Pbo+MTXGLM 50 & 100 mg +MTX CombinedMedian % change from baseline
 BLWk 14/24BLWk 14/24Pbo+MTXGLM (50&100) + MTX
GO-FORWARD (MTX-IR)
LIPID MARKERS (mg/dL)      
Triglycerides103.5108.0108.0113.01.93.7
Total cholesterol194.0199.0198.5213.0###1.08.4***
HDL61.059.060.562.0###0.05.4**
T chol/HDL3.173.263.353.37#1.902.78
LDL107.5111.0112.0121.0##3.311.6***
LDL subfractions      
Mean LDL size (nM)21.321.221.221.6###0.01.0***
Large LDLs (mmol/L)465.5465.0457.0537.0###3.421.5**
Small LDLs (mmol/L)543.0641.0648.0484.0##4.3-10.5***
ApoB/A10.520.540.570.54-1.08-3.78
INFLAMMATORY MARKERS      
High sensitivity CRP (mg/dL)7.06.09.72.1###-10.4-70.7***
GO-BEFORE (MTX-naïve)
LIPID MARKERS (mg/dL)      
Triglycerides114.0113.5107.0114.0-2.04.1
Total cholesterol193.0199.0##191.0202.0###4.04.1
HDL58.056.057.059.0##0.62.5
T chol/HDL3.283.56#3.373.344.80.79
LDL109.0116.0###108.0115.5###6.32.7
LDL subfractions      
Mean LDL size (nM)21.221.4##21.221.5###0.50.9
Large LDLs (mmol/L)406.0479.0##464.5544.0###11.88.0
Small LDLs (mmol/L)679.0538.0644.5516.0###-10.4-16.9
ApoB/A10.560.59##0.580.53###-2.0-3.84
INFLAMMATORY MARKERS      
High sensitivity CRP (mg/L)13.44.5###12.42.1##-49.6-71.7***
#,
##,
###p <=0.05, 0.01, 0.001, resp., for within-group change from baseline.
*,
**,
***p <=0.05, 0.01, 0.001, resp., GLM+MTX vs Pbo+MTX

Conclusion:

This is the first demonstration of favorable changes in LDL sub-fractions in response to anti-TNF therapy. Despite increase in TC & LDL, the atherogenic indices remained stable and CV-related inflammatory markers improved. A suggestion of lower incidence of CV events (not adjudicated) was noted in GLM+MTX treated pts.

To cite this abstract, please use the following information:
Bathon, J., Wasko, M. C., Hsia, E. C., Kirkham, B., Fleischmann, Roy, Genovese, M.C., et al; Golimumab and Cardiovascular Disease in Inflammatory Arthritides [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1682
DOI: 10.1002/art.26756

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