To examine how treatment of rheumatoid arthritis (RA) with anti-tumour necrosis factor alpha antagonists (anti-TNF) and B-cell targeting rituximab influences novel markers of atherosclerosis and inflammation, such as atheroprotective natural IgM antibodies against phosphorylcholine (anti-PC), oxidised low-density lipoprotein (oxLDL) and apolipoproteins.
In a prospective study 215 patients with RA were enrolled of whom 85.6% were seropositive, aged 57.9 ± 12.4 years, with mean disease duration 8.5 (5-15) years. 162 patients were treated with anti-TNF and 53 with rituximab for one year. The patients were assessed and blood sampled at 0, 3, 6 and 12 months. IgM anti-PC and oxLDL were determined by ELISA and apolipoproteins by immunoturbidimetry.
IgM anti-PC increased by 26% during anti-TNF treatment, p<0.001, while decreased by 14% on rituximab, p=0.023, after 12 months of treatment. Patients in remission after 12 months, DAS28<2.6, had higher baseline anti-PC levels compared with those not in remission in both anti-TNF, p=0.007, and rituximab-treated subjects, p=0.041. In both treatment groups, levels of oxLDL increased temporarily at three months but apoA1 improved throughout the study. This effect was inversely correlated with changes in disease activity. The apoB and apoB/apoA1-ratio remained stable throughout the whole study period.
Anti-TNF treatment demonstrated a favourable long-term effect on anti-PC levels. Low levels of IgM anti-PC may identify immune-deficient state and predict inferior therapy response. Biological therapies increased the level of the anti-atherogenic lipid apoA1. The impact of these effects on future CVD events deserves further studies.