Current therapeutic guidelines for immune-mediated inflammatory diseases (IMIDs) contraindicate
the administration of tumour necrosis factor inhibitors (TNFis) in advanced heart
failure (HF) and highlight the potential risk for new-onset HF. The current evidence
has low certainty, and the results of studies in the past two decades have even challenged
the recommendations regarding the impact of TNFis on the risk of HF.The objective
was to systematically synthesize data on the risk of HF in TNFi-treated groups compared
to non-treated controls in IMIDs.A systematic search was conducted in August 2023.
Randomized controlled trials (RCTs) and non-randomized observational studies of IMID
patients comparing groups receiving TNFis to non-TNFi-exposed controls were included.
The outcome was the incidence of worsening, de novo, and composite HF. Random-effects
meta-analysis was conducted using risk ratios (RR) with 95% confidence intervals (CIs)
to pool data.The systematic search identified 49 studies, with 45 included in the
quantitative analysis. For the worsening of HF, the pooled results of non-randomized
studies showed no statistically significant risk-increasing effect of TNFis (RR =
1.18, 95% CI: 0.69-2.00). Analyses from both RCTs and non-randomized data indicated
no increased risk of de novo HF in the TNFi-group compared to controls (RR = 0.87,
95% CI: 0.60-1.25 and RR = 0.86, 95% CI: 0.64-1.14, respectively). Similarly, no increased
risk was found for composite (worsening and de novo) HF in the TNFi-treated group
versus controls, pooling non-randomized data.Our findings indicate that TNFi-treated
IMID patients do not have an increased risk for developing de novo HF, and no statistically
significant risk enhancement could be observed in the risk of worsening HF with TNFis.
Updating IMID guidelines should be considered regarding TNFis' non-risk increasing
effect on de novo HF, whereas further validating data on the risk of worsening HF
in TNFi-treated IMID patients is needed.
