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P448 Biologic therapy and immunodulators are associated with decreased risk of cardiovascular events in patients with immune-mediated inflammatory diseases: a systematic review and meta-analysis

Fumery M.*1, Singh A.2, Khera R.3, Prokop L.4, Curtis J.5, Sandborn W.6, Singh S.6

1Amiens University Hospital, Department of Gastroenterology and Hepatology, Amiens, France 2University of California San Diego, La Jolla, Rheumatology, San Diego, United States 3University of Texas Southwestern Medical Center, Divsion of Cardiology, Dallas, United States 4Mayo Clinic, Rochester, United States 5University of Alabama, Clinical immunology and Rheumatology, Alabama, United States 6University of California San Diego, Department of Gastroenterology, La Jolla, United States

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).

Table 1

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.

Conclusion

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.