Patients with rheumatoid arthritis (RA) experience an increased risk of cardiovascular disease. What is unclear, however, is the role that disease-modifying anti-rheumatic drug (DMARD) therapy plays in that risk. In an effort to investigate the question, Christina Charles-Schoeman, MD, MS, a rheumatologist at Ronald Reagan UCLA Medical Center in Los Angeles, and colleagues analyzed data from the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial and published their results in the March issue of Arthritis & Rheumatology.1 In their paper, the researchers described the cholesterol data from the first randomized, placebo-controlled, long-term study of early RA patients.
TEAR included a population of patients with very early RA. These individuals were primarily seropositive and had high disease activity at baseline. As expected, both body mass index (BMI) and smoking use were strongly associated over time with higher total cholesterol, low-density lipoprotein cholesterol (LDL-C) and total cholesterol/high-density lipoprotein cholesterol (HDL-C) ratios, as well as lower HDL-C levels. Of the 416 patients participating in the two-year trial, three died from cardiac disorders.
The investigators analyzed the relationship between treatment and cholesterol levels and found that patients treated with either biologic or non-biologic therapies who experienced decreases in RA disease activity also had increases in cholesterol. “It really confirms what we have thought,” explains Dr. Charles-Schoeman in an interview with The Rheumatologist. Specifically, decreased inflammation was associated with increased cholesterol levels (total cholesterol, LDL-C and HDL-C).
Dr. Charles-Schoemen explains that rheumatologists have noticed this effect in the clinic and some, along with their patients, have become concerned. However, she points out that, “In terms of what it means, we don’t know yet.” As she notes, although lipoprotein is frequently analyzed for its role in carrying cholesterol and influencing risk for cardiovascular disease, lipoprotein plays other roles as well, one or more of which may be affected by RA treatments. In particular, Dr. Charles-Schoeman describes HDL as a very interesting and complicated particle that likely has multiple biological functions.
In all treatment groups, changes in cholesterol levels were associated with decreases in inflammation as measured by C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and disease activity score (DAS28). Thus, the therapies effectively treated RA, while simultaneously increasing cholesterol levels. When the investigators looked more closely at the cohort, they found that two years of triple therapy was associated with a higher HDL-C, and lower LDL-C and total cholesterol/HDL-C ratios when compared with two years of methotrexate (MTX) monotherapy or MTX + etanercept (ETA). Although the patients who responded to therapy had marked increases in cholesterol at six months, these changes were not maintained throughout the two-year trial.