Effect of Drug Therapy on Net Cholesterol Efflux Capacity of High-Density Lipoprotein–Enriched Serum in Rheumatoid Arthritis

the TETRAD Investigators

    Research output: Contribution to journalArticle

    16 Citations (Scopus)

    Abstract

    Objective: Patients with rheumatoid arthritis (RA) have an increased risk of coronary heart disease (CHD). Some RA therapies may modify this risk, but the underlying mechanisms are unclear. The cholesterol efflux capacity of high-density lipoprotein (HDL) is associated with a reduced CHD risk in non-RA populations; however, inflammation may impair the function of HDL. The aim of this study was to evaluate whether reduced inflammation resulting from treatment with methotrexate (MTX), adalimumab (ADA), or tocilizumab (TCZ) would increase the net cholesterol efflux capacity of HDL in patients with RA. Methods: A longitudinal multicenter study repository (Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository) provided clinical information for and serum samples from 70 patients with RA before and 6 months after starting treatment with a new drug (MTX [n = 23], ADA [n = 22], or TCZ [n = 25]). Disease activity was measured using the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR). The net cholesterol efflux capacity was measured in paired serum samples using THP-1 macrophages, and total cellular cholesterol was measured by fluorometric assay. Results: The DAS28-ESR decreased with all treatments (P < 0.001). Net cholesterol efflux capacity was not significantly changed after 6 months of new RA therapy (mean ± SD 36.9 ± 17.3% units at baseline versus 38.0% ± 16.9% units at 6 months [P = 0.58]). However, change in net cholesterol efflux capacity was associated with change in the DAS28-ESR (ρ = −0.25, P = 0.04). In a post hoc analysis of patients with impaired net cholesterol efflux capacity at baseline, treatment with TCZ resulted in significant improvement in net cholesterol efflux capacity (21.9 ± 14.7% units at baseline versus 31.3% ± 12.8% units at 6 months [P < 0.02]), but this was not observed with MTX or ADA. Conclusion: Net cholesterol efflux capacity of HDL cholesterol did not change significantly after 6 months of new RA therapy, except in patients with impaired baseline cholesterol efflux capacity who were receiving TCZ. Change in disease activity was associated with change in the net cholesterol efflux capacity.

    Original languageEnglish (US)
    Pages (from-to)2099-2105
    Number of pages7
    JournalArthritis and Rheumatology
    Volume68
    Issue number9
    DOIs
    StatePublished - Sep 1 2016

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    Rheumatoid Arthritis
    Cholesterol
    Drug Therapy
    Serum
    Blood Sedimentation
    HDL Lipoproteins
    Methotrexate
    Joints
    Therapeutics
    Coronary Disease
    Inflammation
    HDL Cholesterol
    Multicenter Studies
    Arthritis
    Longitudinal Studies
    Macrophages
    Databases
    tocilizumab
    Pharmaceutical Preparations

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Rheumatology
    • Immunology

    Cite this

    Effect of Drug Therapy on Net Cholesterol Efflux Capacity of High-Density Lipoprotein–Enriched Serum in Rheumatoid Arthritis. / the TETRAD Investigators.

    In: Arthritis and Rheumatology, Vol. 68, No. 9, 01.09.2016, p. 2099-2105.

    Research output: Contribution to journalArticle

    @article{7fe0f3af3787431088e16dc32ae744e7,
    title = "Effect of Drug Therapy on Net Cholesterol Efflux Capacity of High-Density Lipoprotein–Enriched Serum in Rheumatoid Arthritis",
    abstract = "Objective: Patients with rheumatoid arthritis (RA) have an increased risk of coronary heart disease (CHD). Some RA therapies may modify this risk, but the underlying mechanisms are unclear. The cholesterol efflux capacity of high-density lipoprotein (HDL) is associated with a reduced CHD risk in non-RA populations; however, inflammation may impair the function of HDL. The aim of this study was to evaluate whether reduced inflammation resulting from treatment with methotrexate (MTX), adalimumab (ADA), or tocilizumab (TCZ) would increase the net cholesterol efflux capacity of HDL in patients with RA. Methods: A longitudinal multicenter study repository (Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository) provided clinical information for and serum samples from 70 patients with RA before and 6 months after starting treatment with a new drug (MTX [n = 23], ADA [n = 22], or TCZ [n = 25]). Disease activity was measured using the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR). The net cholesterol efflux capacity was measured in paired serum samples using THP-1 macrophages, and total cellular cholesterol was measured by fluorometric assay. Results: The DAS28-ESR decreased with all treatments (P < 0.001). Net cholesterol efflux capacity was not significantly changed after 6 months of new RA therapy (mean ± SD 36.9 ± 17.3{\%} units at baseline versus 38.0{\%} ± 16.9{\%} units at 6 months [P = 0.58]). However, change in net cholesterol efflux capacity was associated with change in the DAS28-ESR (ρ = −0.25, P = 0.04). In a post hoc analysis of patients with impaired net cholesterol efflux capacity at baseline, treatment with TCZ resulted in significant improvement in net cholesterol efflux capacity (21.9 ± 14.7{\%} units at baseline versus 31.3{\%} ± 12.8{\%} units at 6 months [P < 0.02]), but this was not observed with MTX or ADA. Conclusion: Net cholesterol efflux capacity of HDL cholesterol did not change significantly after 6 months of new RA therapy, except in patients with impaired baseline cholesterol efflux capacity who were receiving TCZ. Change in disease activity was associated with change in the net cholesterol efflux capacity.",
    author = "{the TETRAD Investigators} and Ormseth, {Michelle J.} and Yancey, {Patricia G.} and Solus, {Joseph F.} and {Louis Bridges}, S. and Curtis, {Jeffrey R.} and Linton, {MacRae F.} and Sergio Fazio and Davies, {Sean S.} and Roberts, {L. Jackson} and Vickers, {Kasey C.} and Valentina Kon and {Michael Stein}, C. and Bingham, {Clifton O.} and Cofield, {Stacey S.} and Richard Furie and Gregersen, {Peter K.} and Genovese, {Mark C.} and Robinson, {William H.} and Levesque, {Marc C.} and Moreland, {Larry W.} and Nigrovic, {Peter A.} and Shadick, {Nancy A.} and O'Dell, {James R.} and Thiele, {Geoffrey M.} and St.Clair, {E. William} and Striebich, {Christopher C.}",
    year = "2016",
    month = "9",
    day = "1",
    doi = "10.1002/art.39675",
    language = "English (US)",
    volume = "68",
    pages = "2099--2105",
    journal = "Arthritis and Rheumatology",
    issn = "2326-5191",
    publisher = "John Wiley and Sons Ltd",
    number = "9",

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    TY - JOUR

    T1 - Effect of Drug Therapy on Net Cholesterol Efflux Capacity of High-Density Lipoprotein–Enriched Serum in Rheumatoid Arthritis

    AU - the TETRAD Investigators

    AU - Ormseth, Michelle J.

    AU - Yancey, Patricia G.

    AU - Solus, Joseph F.

    AU - Louis Bridges, S.

    AU - Curtis, Jeffrey R.

    AU - Linton, MacRae F.

    AU - Fazio, Sergio

    AU - Davies, Sean S.

    AU - Roberts, L. Jackson

    AU - Vickers, Kasey C.

    AU - Kon, Valentina

    AU - Michael Stein, C.

    AU - Bingham, Clifton O.

    AU - Cofield, Stacey S.

    AU - Furie, Richard

    AU - Gregersen, Peter K.

    AU - Genovese, Mark C.

    AU - Robinson, William H.

    AU - Levesque, Marc C.

    AU - Moreland, Larry W.

    AU - Nigrovic, Peter A.

    AU - Shadick, Nancy A.

    AU - O'Dell, James R.

    AU - Thiele, Geoffrey M.

    AU - St.Clair, E. William

    AU - Striebich, Christopher C.

    PY - 2016/9/1

    Y1 - 2016/9/1

    N2 - Objective: Patients with rheumatoid arthritis (RA) have an increased risk of coronary heart disease (CHD). Some RA therapies may modify this risk, but the underlying mechanisms are unclear. The cholesterol efflux capacity of high-density lipoprotein (HDL) is associated with a reduced CHD risk in non-RA populations; however, inflammation may impair the function of HDL. The aim of this study was to evaluate whether reduced inflammation resulting from treatment with methotrexate (MTX), adalimumab (ADA), or tocilizumab (TCZ) would increase the net cholesterol efflux capacity of HDL in patients with RA. Methods: A longitudinal multicenter study repository (Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository) provided clinical information for and serum samples from 70 patients with RA before and 6 months after starting treatment with a new drug (MTX [n = 23], ADA [n = 22], or TCZ [n = 25]). Disease activity was measured using the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR). The net cholesterol efflux capacity was measured in paired serum samples using THP-1 macrophages, and total cellular cholesterol was measured by fluorometric assay. Results: The DAS28-ESR decreased with all treatments (P < 0.001). Net cholesterol efflux capacity was not significantly changed after 6 months of new RA therapy (mean ± SD 36.9 ± 17.3% units at baseline versus 38.0% ± 16.9% units at 6 months [P = 0.58]). However, change in net cholesterol efflux capacity was associated with change in the DAS28-ESR (ρ = −0.25, P = 0.04). In a post hoc analysis of patients with impaired net cholesterol efflux capacity at baseline, treatment with TCZ resulted in significant improvement in net cholesterol efflux capacity (21.9 ± 14.7% units at baseline versus 31.3% ± 12.8% units at 6 months [P < 0.02]), but this was not observed with MTX or ADA. Conclusion: Net cholesterol efflux capacity of HDL cholesterol did not change significantly after 6 months of new RA therapy, except in patients with impaired baseline cholesterol efflux capacity who were receiving TCZ. Change in disease activity was associated with change in the net cholesterol efflux capacity.

    AB - Objective: Patients with rheumatoid arthritis (RA) have an increased risk of coronary heart disease (CHD). Some RA therapies may modify this risk, but the underlying mechanisms are unclear. The cholesterol efflux capacity of high-density lipoprotein (HDL) is associated with a reduced CHD risk in non-RA populations; however, inflammation may impair the function of HDL. The aim of this study was to evaluate whether reduced inflammation resulting from treatment with methotrexate (MTX), adalimumab (ADA), or tocilizumab (TCZ) would increase the net cholesterol efflux capacity of HDL in patients with RA. Methods: A longitudinal multicenter study repository (Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository) provided clinical information for and serum samples from 70 patients with RA before and 6 months after starting treatment with a new drug (MTX [n = 23], ADA [n = 22], or TCZ [n = 25]). Disease activity was measured using the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR). The net cholesterol efflux capacity was measured in paired serum samples using THP-1 macrophages, and total cellular cholesterol was measured by fluorometric assay. Results: The DAS28-ESR decreased with all treatments (P < 0.001). Net cholesterol efflux capacity was not significantly changed after 6 months of new RA therapy (mean ± SD 36.9 ± 17.3% units at baseline versus 38.0% ± 16.9% units at 6 months [P = 0.58]). However, change in net cholesterol efflux capacity was associated with change in the DAS28-ESR (ρ = −0.25, P = 0.04). In a post hoc analysis of patients with impaired net cholesterol efflux capacity at baseline, treatment with TCZ resulted in significant improvement in net cholesterol efflux capacity (21.9 ± 14.7% units at baseline versus 31.3% ± 12.8% units at 6 months [P < 0.02]), but this was not observed with MTX or ADA. Conclusion: Net cholesterol efflux capacity of HDL cholesterol did not change significantly after 6 months of new RA therapy, except in patients with impaired baseline cholesterol efflux capacity who were receiving TCZ. Change in disease activity was associated with change in the net cholesterol efflux capacity.

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