POS0213 EFFECT OF EARLY ETANERCEPT TREATMENT ON CIRCULATING LIPOPROTEINS DIFFERS TO TREATMENT WITH METHOTREXATE AND IS MODULATED BY CLINICAL DISEASE ACTIVITY

Abstract

BackgroundA reduction in serum lipids such as total cholesterol (TC) and low-density lipoprotein (LDL) has been associated with increased risk of cardiovascular events in active RA, paradoxical to the general population1. The effect of DMARDs and active inflammation on lipid profiles has been investigated in RA but detailed lipid profiling has been lacking in very early disease and across the spectrum of disease activity.ObjectivesIn a treatment naïve early RA trial cohort, we sought to compare circulating lipid profiles between patients treated with first line etanercept + methotrexate (ETN+MTX) versus methotrexate treat-to-target (MTX-TT) regime and between clinical remission and high disease activity.MethodsVEDERA trial (Very early Etanercept and Methotrexate versus Methotrexate with/without Delayed Etanercept in RA) randomised 120 treatment-naïve RA patients to either first-line ETN+MTX or MTX-TT regime with escalation to ETN+MTX if not in DAS28ESR remission at week 242. TC, triglycerides (TG), high density lipoprotein (HDL) and LDL were measured; apolipoproteins and atherogenic indices such as TC/HDL, atherogenic index of plasma (AIP) and apolipoprotein B/A-i ratio (aporatio) were calculated at baseline, weeks 12, 24 and 48. Linear mixed effects regression was used to test the effect of treatment on lipids and atherogenic indices in states of remission (DAS28-ESR ≤ 2.6) and high disease activity (DAS28-ESR > 5.1).ResultsBaseline clinical characteristics of individuals1 and lipid profiles including atherogenic indices were comparable between the two treatment groups (Table 1).Table 1.Baseline lipids (mmol/L) and atherogenic indices in VEDERA. Median with interquartile range and n/N (%) reported.Total, N = 120MTX_TT, N = 60ETN+MTX, N = 60TC4.69 (4.03,5.25)4.70 (4.04,5.42)4.69 (4.01,5.18)TG1.15 (0.90,1.41)1.18 (0.92,1.32)1.10 (0.89,1.55)HDL1.28 (1.04,1.53)1.29 (1.04,1.57)1.27 (1.05,1.48)LDL2.87 (2.22,3.27)2.87 (2.27,3.19)2.84 (2.01,3.29)TC/HDL3.53 (3.01,4.16)3.53 (3.00,4.14)3.58 (3.08,4.17)AIP-0.06 (-0.20,0.09)-0.06 (-0.22,0.08)-0.06 (-0.17,0.13)Aporatio0.63 (0.54,0.74)0.62 (0.54,0.74)0.64 (0.55,0.74)In clinical remission, a lowering of atherogenic indices and TC, TG, LDL levels as well as a rise in predicted HDL levels were observed. In high disease activity, both HDL and LDL were increased along with the atherogenic indices TC/HDL-C, AIP and aporatio. However, the predicted values at different weeks did not reach statistical significance (not shown).Treatment with MTX-TT and ETN+MTX had opposing effects on predicted HDL levels in remission and high-disease activity (Figure 1). In remission, MTX-TT treatment resulted in a predicted rise in HDL whilst with ETN+MTX a small reduction was observed (estimate 0.004, p 0.02). Similar trends were observed for HDL in high disease activity (p 0.5). In remission, both treatments resulted in a reduction in LDL (p 0.5), whilst in high disease activity ETN+MTX treatment resulted in a modest rise in LDL compared to MTX-TT (p 0.06). At weeks 24 and 48, significant differences were observed in LDL values between treatment groups in high disease activity (estimate 0.57, p 0.05 and estimate 1.13, p 0.04 respectively).ConclusionEffect of early ETN treatment on HDL, and to a lesser extent LDL, differs from MTX and is modulated by clinical disease activity. Further investigation is needed to understand the basis for these findings and the clinical implication of observed differences in LDL and HDL. These data may indicate direct effect of therapies on the qualitative and functional components of metabolic lipid pathway.