Table 1

Effects of biological DMARDs on cardiovascular and arterial stiffness in patients with rheumatoid arthritis (RA) and other inflammatory arthropathies

DMARDMechanism of actionCardiovascular and arterial stiffness effectsReference
Adalimumab, infliximab, etanercept,
certolizumab,
golimumab
Tumour necrosis factor (TNF) inhibitors
  1. Reduction of PWV in patients* using TNF inhibitors versus controls (−0.50±0.78 m/s vs 0.05±0.54 m/s; p=0.002).

  2. Reduction in endothelial dysfunction† (0.987, 95% CI (0.64 to 1.33), p < 0.0001).

  3. 30% reduction in cerebrovascular disease (RR 0.70, 95% CI 0.54 to 0.90), 41% reduction in acute myocardial infarction (RR 0.59, 95% CI 0.36 to 0.97) and 43% for stroke (RR 0.57, 95% CI 0.35 to 0.92).*

  4. A greater reduction in PWV was found for etanercept and adalimumab versus infliximab.†

  5. Both certolizumab* and golimumab* have studies which describe their cardiovascular safety. However, more studies are needed to evaluate their impact on PWV.

  6. Reduction on cIMT progression (−0.002 (–0.038, 0.030) mm vs 0.030 (0.011, 0.043) mm, respectively; p=0.01).

  7. Improvement in FMD 14 days (mean±SD): 6.1%±3.9%; median: 5.7%) and 12 months (mean±SD: 7.4%±2.8%; median: 6.9% at month 12) after day 0 (mean: 4.5%±4.0%; median: 3.6%; p=0.03 and p<0.001, respectively) in non-responders to conventional treatment.

65 66 70 71 77–80
RituximabAnti-CD20 monoclonal antibody
  1. A 30%, 22% and 81% improvement on FMD was documented at weeks 2, 6 and 16 of treatment, respectively, (3.92%±1.47 vs 7.24%±3.35, p=0.02 for week 16).†

  2. A tendency towards a reduction in PWV and AIX was observed, nonetheless studies with a greater number of patients are needed.†

  3. In responders to treatment, it improves the elastic properties in the major arteries with decreased stiffness (SI decreased by 57%) and arterioles (RI decreased by 24%).

  4. Significant reduction on cIMT to responders to treatment at 6 months by 11%. Also, there was a correlation between decreasing cIMT and IgM RF levels (r=0.49, p<0.001).

  5. In patients treated for 1 year, significant reduction in PWV and blood pressure levels, without significant changes in TC, HDL-c or TC/HDL-c.

81–86
TocilizumabAnti-IL-6 monoclonal antibody
  1. Lipid profile components are higher in patients using tocilizumab without a clear relation with a higher cardiovascular risk.†

  2. Improvement in FMD after 6 months of treatment (3.3%±0.8 vs 5.2%±1.9, p=0.003) and a reduction in PWV (8.2±1.2 vs 7.0±1.0 m/s, p<0.001).†

  3. There is a tendency in favour of tocilizumab regarding its effects on arterial stiffness and endothelial dysfunction, however more studies with a higher number of patients are needed.†

  4. When compared with rituximab and abatacept in the multivariate analysis, at 3 months, patients treated with tocilizumab had a significant higher reduction of CVD risk by PWV.

  5. Blood pressure levels where significantly lower after 3 months of treatment compared with abatacept.

  6. There is a tendency in favour of tocilizumab regarding its effects on arterial stiffness and endothelial dysfunction, however more studies with a higher number of patients are needed.†

58 83 87–89
AbataceptInhibitor of T cell activation by Inhibiting CD80/86-CD28
  1. Significant reduction in PWV after 6 months of treatment documented on a small study (n=21)(8.5±3.9 vs 9.8±2.9 m/s, p=0.02).†

  2. More studies are needed to establish its effect.

83 90
AnakinraRecombinant antagonist of IL-1 receptor
  1. Improvement of FMD (5.3%±3.0 vs 9.7%±3.3, p<0.001), compared with placebo (5.3%±3.0 vs 4.8%±2.7, p=0.9).† Additional studies also found an improvement in FMD.

  2. No impact has been observed in PWV.

58 83
Baricitinib and tofacitinibJanus kinase inhibitors
  1. An elevation in HDL and LDL along with triglycerides is documented without a rise in LDL/HDL ratio. This effect could be related to a downregulated IL-6 response. In spite of this, there is a reduction in cardiovascular risk and cIMT.†

  2. There is a lower incidence of cerebrovascular disease similar to that of TNF inhibitors. However, studies with a longer follow-up time to observe cardiovascular safety on RA are needed as are studies evaluating its impact on PWV.

  3. For patients who had cIMT >1.10 mm at baseline, after a year of treatment; cIMT and AIX@75 had a significant decrease (cIMT 0.05±0.026 mm; p<0.05 and 38.89±3.59 and 35.22%±4.85%, p<0.01).

  4. An upregulating effect on TC levels has been identified, without a demonstrated increase in CVD risk.

84 91
  • *Patients with inflammatory arthropathies including RA.

  • †Patients with RA.

  • AIX, aortic augmentation index; cIMT, carotid intima–media thickness; CVD, cardiovascular disease; DMARDs, disease-modifying antirheumatic drugs; FMD, flow-mediated dilation; HDL-c, high-density lipoprotein-cholesterol; IL, interleukin; LDL, low-density lipoprotein; PWV, pulse wave velocity; ; RF, rheumatoid factor; RI, reflection index; RR, relative risk; SI, stiffness index; TC, total cholesterol.