TNF inhibitors use associated with favorable CVD markers in Rheumatoid Arthritis patients

Netherlands: A new study found that tumor necrosis factor (TNF) inhibitors have a favorable effect on cardiovascular disease risk by stabilizing intima-media thickness (IMT), decreasing pulse wave velocity (PWV) and augmentation index (AIx) in patients with Rheumatoid arthritis. The study results were published in the journal Clinical Rheumatology. 

There is an increased risk of cardiovascular disease and its associated mortality in Rheumatoid arthritis (RA). RA patients also have an increased risk of cardiovascular risk factors. Past literature suggests that cardiovascular risk can be reduced by controlling inflammation. Based on the hypothesis that TNF inhibitors reduce inflammation in the arterial wall and thus have a favorable effect on the cardiovascular health of RA patients, researchers conducted a systematic review and meta-analysis to evaluate the effect of TNF inhibitors on arterial stiffness (as measured with PWV and AIx) and IMT in RA patients. 

Following the PRISMA guidelines, databases like MEDLINE, EMBASE, clinicaltrials.gov, and the WHO International Clinical Trials registry were searched from inception until 15 September 2020. Eligible studies included studies, where at least 80% of the study population consisted of RA patients, intervention with a TNF inhibitor or any combination of drugs including a TNF inhibitor, and the outcome measure, was either PWV, AIx, and/or IMT. The primary outcome of measurement was the effects of TNF-inhibiting treatment on IMT, PWV, and AIx. Data comparison was done using the random effects model and the I2 statistic was used to measure heterogenicity. A risk of bias assessment was performed using an adjusted Downs and Black checklist. 

Key findings of the study: 

• Thirty studies were identified from 1436 records, of which 23 were included in the meta-analysis.
• TNF treatment showed a decrease in PWV and AIx after treatment (PWV: mean difference (MD) −0.51 m/s; AIx: MD −0.57%).
• IMT showed a slight increase in the first months of follow-up, that disappeared in the long-term (overall timepoints MD −0.01 mm (95% CI: −0.04, 0.02), p=0.615). 
• There was high Heterogeneity in the overall analyses and subgroups with long follow-up periods (≥12 months).
• There were mixed results on the effects of TNF inhibitors on the surrogate markers from the included studies.
• The PWV and AIx decreased over time, while IMT remains stable as per the pooled results. 

Thus, this is the first study that analyzed the effect of TNF inhibitors on cardiovascular risk factors. TNF inhibitors decreased the number of cardiovascular events in RA patients. 

Further reading: Abdulmajid, B., Blanken, A.B., van Geel, E.H. et al. Effect of TNF inhibitors on arterial stiffness and intima media thickness in rheumatoid arthritis: a systematic review and meta-analysis. Clin Rheumatol (2023). https://doi.org/10.1007/s10067-023-06505-y