Session Information
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Patients with rheumatoid arthritis
(RA) have increased coronary heart disease risk. Some RA therapies may modify
this risk, but underlying mechanisms are unclear. The cholesterol efflux
capacity of HDL (the ability of HDL to remove cholesterol from lipid-laden
macrophages) is associated with reduced coronary heart disease risk in non-RA
populations. Inflammation can impair the
function of HDL. We hypothesized that better control of inflammation with methotrexate,
adalimumab and tocilizumab
would increase the net cholesterol efflux capacity of HDL-enriched serum in
patients with RA.
Methods: A longitudinal multi-center study (Treatment
Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository or
TETRAD) obtained clinical information and serum samples from 70 patients with RA before and 6
months after starting a new therapy for RA. RA disease activity was measured by
DAS28. The study included patients
starting methotrexate (n=23), adalimumab (n=22), and tocilizumab (n=25). Net cholesterol efflux capacity of HDL-enriched
serum was measured on paired serum samples using THP-1 macrophages and a fluorometric assay for cholesterol measurement. Wilcoxon
signed rank tests were used to compare paired continuous data.
Results: DAS28 score decreased
significantly in all three groups after treatment (P<0.001). Net cholesterol
efflux capacity (mean± SD) was not significantly changed after 6 months of new
therapy (baseline, 36.9% units ± 17.3 vs. 6 months, 38.0% units ± 16.9, P=0.58)
(Table). Change in cholesterol efflux capacity was modestly associated with
change in DAS28 (rho=-0.25, P=0.04) (Figure). Among patients with baseline impaired
net cholesterol efflux capacity (efflux capacity below mean), tocilizumab resulted in modest, significant improvement in
net cholesterol efflux (baseline, 21.9% units ± 14.7 vs. 6 months, 31.1% units
± 12.8, P=0.02), but this was not observed with methotrexate or adalimumab users or among those with normal baseline efflux
capacity (all P>0.05).
Conclusion: The net cholesterol efflux capacity of HDL did
not change significantly after 6 months of new RA therapy but was weakly
associated with change in disease activity. Among patients with impaired net
cholesterol efflux capacity at baseline, there was a modest improvement after
treatment with tocilizumab, but not with methotrexate
or adalimumab. Further studies are needed to define the relationship between cholesterol
efflux capacity and coronary heart disease risk in patients with RA.
Table: Net cholesterol efflux capacity before and after
DMARD or biologic therapy
|
Baseline |
6 Months |
Absolute Change |
P value |
|
|
All patients |
||||
|
All drugs (N=70) |
36.9% ± 17.3 |
38.0% ± 16.9 |
1.1% ± 16.6 |
0.58 |
|
Methotrexate (N=23) |
41.2% ±13.9 |
38.0% ± 17.5 |
-3.3% ± 20.2 |
0.38 |
|
Adalimumab (N=22) |
36.1% ±16.8 |
38.5% ± 18.2 |
2.3% ± 14.6 |
0.44 |
|
Tocilizumab (N=25) |
33.7% ± 20.1 |
37.6% ± 15.8 |
3.9% ± 14.2 |
0.23 |
|
Patients with impaired baseline net cholesterol efflux |
||||
|
All drugs (N=37) |
24.1% ±11.3 |
31.0% ±12.4 |
6.8% ±15.7 |
0.02 |
|
Methotrexate (N=10) |
28.8% ± 9.5 |
34.0% ± 12.6 |
5.1% ± 19.7 |
0.80 |
|
Adalimumab (N=12) |
22.9% ± 6.6 |
28.0% ± 14.5 |
5.1% ± 14.4 |
0.27 |
|
Tocilizumab (N=15) |
21.9% ± 14.7 |
31.3% ± 12.8 |
9.4% ± 14.4 |
0.02 |
To cite this abstract in AMA style:
Ormseth MJ, Bridges SL Jr., Curtis JR, Solus JF, Yancey P, Linton MF, Davies S, Roberts LJ II, Vickers KC, Kon V, Fazio S, Stein CM. Effect of Drug Therapy on Net Cholesterol Efflux Capacity of HDL-Enriched Serum in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/effect-of-drug-therapy-on-net-cholesterol-efflux-capacity-of-hdl-enriched-serum-in-rheumatoid-arthritis/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/effect-of-drug-therapy-on-net-cholesterol-efflux-capacity-of-hdl-enriched-serum-in-rheumatoid-arthritis/