Background: Immune-mediated inflammatory diseases (IMIDs) are associated with an increased risk of cardiovascular events. Studies, particularly in patients with inflammatory bowel diseases (IBD), have shown variable impact of disease-modifying therapy on cardiovascular risk, in part due to confounding by disease severity. Additionally, comparative cardiovascular risk modification by biologics and immunomodulators is unclear. We conducted a systematic review with meta-analysis, to evaluate the impact of exposure to biologics and immunomodulators on cardiovascular risk in patients with IMIDs.
Methods: Through a systematic literature review through March 2016, we identified cohort studies in adults with IMIDs (IBD, rheumatoid arthritis, psoriasis and psoriatic arthritis and spondyloarthropathies) reporting the association between biologics and immunomodulators and risk of cardiovascular events (myocardial infarction, stroke, cardiovascular mortality). Random-effects meta-analysis, including a priori subgroup analyses based on adjustment for disease severity, was performed.
Results: On meta-analysis of 24 studies, exposure to biologics was associated with a 30% lower risk of cardiovascular events (OR, 0.70; 95% CI, 0.59–0.82), with substantial heterogeneity (I2=66%). Overall magnitude of decline in cardiovascular risk was comparable across IMIDs, cardiovascular event type and location (Table 1). Magnitude of protective association was comparable in studies that adjusted for baseline disease severity (8 studies; OR, 0.68; 95% CI, 0.52–0.88) and those which did not (16 studies; OR, 0.70; 95% CI, 0.56–0.88) (p=0.87).
Similarly, on meta-analysis of 12 studies, exposure to immunomodulators was associated with a 32% lower risk of cardiovascular events (OR, 0.68; 95% CI, 0.57–0.81), with considerable heterogeneity (I2=82%). Overall magnitude of decline in cardiovascular risk with immunomodulators was higher in patients with IBD, and higher for cardiovascular mortality (Table 1). Magnitude of protective association was comparable in studies that adjusted for baseline disease severity (4 studies; OR, 0.73; 95% CI, 0.50–1.06) and those which did not (8 studies; OR, 0.65; 95% CI, 0.53–0.79) (p=0.59). Overall magnitude of decline in cardiovascular risk was comparable with biologic exposure and immunomodulator exposure.
Conclusions: Exposure to biologics and immunomodulators is associated with a lower risk of cardiovascular events in patients with IMIDs. Future studies evaluating the impact of response, rather than just exposure, to therapy, are warranted to determine the effect of modification of specific inflammatory pathways and overall reduction in inflammation, on cardiovascular risk in patients with IMIDs.