Tocilizumab linked to lower cardiovascular risk than TNF inhibitors in RA
Among patients with rheumatoid arthritis, tocilizumab was associated with a decreased risk for major adverse cardiovascular events, compared with TNF inhibitors, whereas conventional synthetic disease-modifying antirheumatic drugs may be linked with an increased risk, according to recent data in Arthritis Care & Research.
“Treatment of RA using disease-modifying anti-rheumatic drugs (DMARDs), including conventional synthetic DMARDs as well as biologic agents, has been associated with decreased risk of cardiovascular events; in contrast, corticosteroids and [NSAIDs] use has been associated with increased risk,” Siddharth Singh, MD, MS, of the University of California San Diego, and colleagues wrote.
“This protective association with biologic therapies may be attributed to better disease control resulting in lower systemic inflammatory burden,” they added. “However, the comparative effect of different biologic and [conventional synthetic] DMARDs on cardiovascular risk has not been well studied.”
To compare the risk for cardiovascular events and stroke associated with conventional synthetic DMARDs, non-TNF biologic drugs and targeted synthetic DMARDs, compared with TNF inhibitors, among patients with RA, Singh and colleagues conducted a systematic review and meta-analysis. The researchers searched for observational cohort or nested case-control studies published through May 8, 2018, focusing specifically on those including patients with RA treated with conventional synthetic DMARDs, TNF inhibitors, non-TNF biologic drugs and targeted synthetic DMARDs, with reporting on cardiovascular and stroke risk.
The initial review identified 9,488 unique studies, of which the researchers reviewed the full texts of 129. Singh and colleagues ultimately selected 14 studies that included active comparator analyses to include in their final analysis. Of these included studies, nine used administrative claims data, four were based on large biologic registries and one was based on a large health care system. The researchers conducted a random effects meta-analysis and estimated ORs.
According to the researchers, tocilizumab (Actemra, Genentech) was associated with a decreased risk for major cardiovascular events compared with TNF inhibitors (OR = 0.59; 95% CI, 0.341). Conventional synthetic DMARDs were associated with an increased risk for major cardiovascular events compared with TNF inhibitors (OR including methotrexate = 1.45 [95% CI, 1.091.93]; OR without methotrexate = 2.57 [95% CI, 1.325]). However, without heterogeneity, there was no difference in cardiovascular risk between abatacept (Orencia, Bristol Myers Squibb) and TNF inhibitors (OR = 0.89; 95% CI, 0.711.11), or between tocilizumab and abatacept (OR = 0.81; 95% CI, 0.571.16).
In addition, based on 11 studies, including a total of 135,053 patients, conventional synthetic DMARDs were associated with an increased risk for stroke compared with TNF inhibitors (OR = 1.17; 95% CI, 1.011.36). However, without heterogeneity, there was no difference in stroke risk between various biologics, including tocilizumab vs. TNF inhibitors, abatacept vs. TNF inhibitors, and tocilizumab vs. abatacept.
“Based on a meta-analysis, there does not appear to be a significant difference in the risk of [major adverse coronary events] and stroke between non-TNF [inhibitors] and TNF [inhibitors] biologics in patients with RA,” Singh and colleagues wrote. “TNF [inhibitors], and potentially by extension other non-TNF [inhibitors] biologics, are associated with a lower risk of cardiovascular events and stroke as compared to [conventional synthetic] DMARDs. This may be related to more effective control of systemic inflammation that may be the primary driver of premature atherosclerosis in patients with RA.” – by Jason Laday
Disclosure: Singh reports research support from the NIH, as well as grants from AbbVie and Pfizer, and consulting fees from AbbVie, AMAG Pharmaceuticals and Takeda. Please see the study for all other authors’ relevant financial disclosures.