Cardiovascular risk associated with conventional, biologic DMARDs characterized
medwireNews: Tocilizumab is associated with a lower risk for major adverse cardiovascular events (MACE) than tumor necrosis factor (TNF) inhibitors among patients with rheumatoid arthritis (RA), whereas the use of conventional DMARDs may be linked to an elevated risk, researchers report.
The systematic review and meta-analysis included 14 observational studies of RA patients aged an average of 51–81 years who were treated with TNF inhibitors, other biologics, or conventional DMARDs.
Siddharth Singh (University of California San Diego, USA) and colleagues demonstrated that patients treated with the interleukin-6 receptor inhibitor tocilizumab had a significant 41% reduced risk for MACE (myocardial infarction, coronary revascularization, or cardiovascular death) compared with those given TNF inhibitors. There was no significant difference in MACE risk among individuals treated with abatacept versus TNF inhibitors, however.
“Several randomized clinical trials have demonstrated increase in [low-density lipoprotein] cholesterol levels in tocilizumab-treated patients with RA,” which has “raised concerns whether tocilizumab may be associated with increased cardiovascular risk,” say the study authors.
“However, our findings of a potentially protective association between tocilizumab use and risk of MACE are reassuring at the very least, suggesting the risk is no higher, and may be lower, than that associated with TNF [inhibitors] in patients with RA,” they add.
On the other hand, Singh and colleagues found that conventional DMARDs were associated with a significant 58% increased MACE risk relative to TNF inhibitors, with a similar pattern of results observed regardless of whether methotrexate was used as the conventional DMARD or not.
The team also investigated the association between different RA treatments and the risk for stroke or transient ischemic attack (TIA), which was reported in eight studies. On meta-analysis, patients treated with tocilizumab and those given TNF inhibitors had a comparable risk, as did patients treated with abatacept versus TNF inhibitors.
Conversely, conventional DMARDs were associated with a significant 19% elevated risk for stroke/TIA compared with TNF inhibitors. This association remained significant when the analysis was restricted to studies in which methotrexate was given as the DMARD, but was not significant in the one study that excluded methotrexate.
These findings “may be related to superior control of inflammation” with TNF inhibitors relative to methotrexate, or possibly due to “lower ongoing exposure to NSAIDs and corticosteroids” with biologics, hypothesize the authors.
And they conclude in Arthritis Care & Research: “Future clinical trials and prospective studies, particularly comparing different non-TNF [inhibitor] biologics and targeted synthetic DMARDs (for example, Janus kinase inhibitors) are warranted to inform the comparative cardiovascular safety of different therapies in patients with RA.”
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