Reducing cardiovascular risk with immunomodulators: a randomised active comparator trial among patients with rheumatoid arthritis

Abstract

ObjectiveRecent large-scale randomised trials demonstrate that immunomodulators reduce cardiovascular (CV) events among the general population. However, it is uncertain whether these effects apply to rheumatoid arthritis (RA) and if certain treatment strategies in RA reduce CV risk to a greater extent.MethodsPatients with active RA despite use of methotrexate were randomly assigned to addition of a tumour necrosis factor (TNF) inhibitor (TNFi) or addition of sulfasalazine and hydroxychloroquine (triple therapy) for 24 weeks. Baseline and follow-up18F-fluorodeoxyglucose-positron emission tomography/CT scans were assessed for change in arterial inflammation, an index of CV risk, measured as an arterial target-to-background ratio (TBR) in the carotid arteries and aorta.Results115 patients completed the protocol. The two treatment groups were well balanced with a median age of 58 years, 71% women, 57% seropositive and a baseline disease activity score in 28 joints of 4.8 (IQR 4.0, 5.6). Baseline TBR was similar across the two groups. Significant TBR reductions were observed in both groups—ΔTNFi: −0.24 (SD=0.51), Δtriple therapy: −0.19 (SD=0.51)—without difference between groups (difference in Δs: −0.02, 95% CI −0.19 to 0.15, p=0.79). While disease activity was significantly reduced across both treatment groups, there was no association with change in TBR (β=0.04, 95% CI −0.03 to 0.10).ConclusionWe found that addition of either a TNFi or triple therapy resulted in clinically important improvements in vascular inflammation. However, the addition of a TNFi did not reduce arterial inflammation more than triple therapy.Trial registration numberNCT02374021.

Endothelial inflammation in patients with Rheumatoid Arthritis treated with Tofacitinib

“…In Solomon et al 33 , vascular in ammation measured by PET-FDG/TC was evaluated in patients randomly assigned to a TNF-α inhibitor vs triple therapy (metothrexate, sulfasalazine and hydroxychloroquine). In this study, both groups improved their disease activity but an association between articular improvement and vascular in ammation was not found.…”

Cardiovascular complications of rheumatoid arthritis

“…Another RCT approach has been to utilize a subclinical CV outcome, which enables measurement of change in an outcome relative to baseline for each therapy. In the recent TARGET RA trial in methotrexate inadequate responders, change in FDG uptake in the aorta and carotid arteries over six months was compared in patients escalated to a TNF inhibitor versus to triple therapy [30 ▪▪ ]. In both groups, FDG uptake decreased by approximately 15% over 6 months and there was no statistically significant difference between treatment groups, thus providing direct proof that reducing vascular inflammation can be accomplished with both a targeted therapy as well as with conventional nontargeted DMARDs.…”

Long-term safety of biologic and targeted synthetic disease modifying drugs in rheumatology

“…A systematic review of RCTs and observational studies in RA found that TNFi use was associated with a reduced risk of all MACE. In a recent RCT, Solomon et al [9 ▪ ], randomized patients with active RA despite use of MTX to either addition of a TNFi or triple therapy for 24 weeks and monitored arterial inflammation with serial PET scans. Both arms showed similar clinically important improvements in vascular inflammation.…”