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Methotrexate Monotherapy vs Combination Therapy to Lower CV Risk in Early RA?

August 17, 2016

For patients with early rheumatoid arthritis (RA), decreases in disease activity after treatment with either methotrexate (MTX) monotherapy or combination therapy were linked to improvements in high-density lipoprotein cholesterol (HDL) function.

Given that abnormal HDL function has been implicated as a potential mechanism of increased cardiovascular disease (CVD) in RA patients, this finding could suggest a potential therapeutic target for CVD risk RA patients.

This is a finding of the Treatment of Early Rheumatoid Arthritis (TEAR) trial recently published online by Charles-Schoeman and colleagues.1 The study was undertaken to assess whether it is more beneficial to treat all patients with early RA with MTX in combination with hydroxychloroquine plus sulfasalazine or in combination with etanercept, or reserve combination therapies for patients who do not respond to MTX alone. The study also looked at which combination of MTX therapy is better.


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In the current analysis, investigators used data from 500 patients in the TEAR trial to evaluate changes in HDL function and HDL-associated proteins in early RA patients treated with one of the three treatment regimens over two years of follow-up. The analysis was done to look at the effect of treatment on HDL given that abnormal HDL function has been implicated as a potential mechanism linked to increased cardiovascular disease (CVD) in RA patients.

Changes in HDL function and HDL-associated proteins were assessed by measuring the anti-oxidant capacity of HDL, paraoxonase 1 (PON-1) activity, HDL-associated haptoglobin (HDL-Hp), HDL-associated apolipoprotein AL (HDL-apoA-1), and myeloperoxidase (MPO) levels at at 0- , 24-, 48-, and 102 weeks.

Disease activity was measured by the disease activity score with 28 joint count (DA28), erythrocyte sedimentation rate (ESR), or C-reactive protein (CRP).

Using mixed effect models that controlled for traditional risk factors for CV, the study found significant associations between decreased RA disease activity (based on the above measures), treatment regimen, prednisone use, and status use with the HDL function over time. In specific, increases in PON1 activity and HDL-apoA-1 levels were associated with decreases in RA disease activity as were decreases in the HDL inflammatory index, MPO, and HDL-Hp.

Based on these results, the authors conclude that further work is “warranted to evaluate abnormal HDL function as a potential mechanism and therapeutic target for CV risk in patients with RA.” ---Julie Gould


 Schoeman CC, Lee YY, Shahbazian A, et al. Improvements in HDL function in early rheumatoid arthritis patients treated with methotrexate monotherapy or combination therapy in the TEAR trial [published online ahead of print August 2, 2016]. Arthritis Rheumatol  doi: 10.1002/art.39833. Treatment of Early Aggressive Rheumatoid Arthritis (TEAR).


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