P2110 - Risk of Major Adverse Cardiovascular Events in Patients With Inflammatory Bowel Diseases or Other Immune-Mediated Inflammatory Disorders on Biologics and Small Molecules: A Systematic Review and Network Meta-Analysis
Shivani Mattay, MD1, Mohammad Zamani, MD2, Dany Saturno, MD3, Edward V.. Loftus, MD4, Matthew Ciorba, MD1, Andres Yarur, MD5, Siddharth Singh, MD6, Parakkal Deepak, MBBS, MS7 1Washington University in St. Louis, St. Louis, MO; 2Tehran University of Medical Sciences, Tehran, Tehran, Iran; 3Washighton University, St. Louis, MO; 4Mayo Clinic College of Medicine and Science, Rochester, MN; 5Cedars-Sinai Medical Center, Los Angeles, CA; 6University of California, San Diego, San Diego, CA; 7Washington University in St. Louis School of Medicine, St. Louis, MO
Introduction: Recent studies raise concern for an increased risk of major adverse cardiovascular events (MACE) with Janus Kinase inhibitors (JAKi) used to treat immune-mediated inflammatory disorders (IMIDs). Our aim was to examine MACE risk with all licensed biologics and small molecules for patients with inflammatory bowel disease and other IMIDs such as psoriasis/Psoriatic arthritis and rheumatoid arthritis.
Methods: Data were obtained from systematic searches (from 1989 to May 31, 2022) in PubMed, Embase, Ovid Medline, Scopus, Cochrane Central, and Clinicaltrials.gov. Comparative studies that assessed a pre-defined MACE risk in patients with IMIDs during treatment with anti-interleukin-23 antibodies (anti-IL-23), anti-interleukin 12/23 antibodies (anti-IL-12/23), anti-tumor necrosis factor-alpha antibodies (anti-TNF-α) or JAKi were included. We performed a network meta-analysis using a random-effects model with results as pooled odds ratios (ORs) with 95% credible intervals (CrIs) according to drug class and disease state.
Results: Among 3,528 studies identified, 40 (including 36 randomized controlled trials [RCTs] and 4 cohort studies) were included in the systematic review, comprising 126,961 patients with IMIDs (Figure 1). Based on the network meta-analysis of RCTs, regardless of disease state, anti-TNF-α (OR, 2.49; 95% CrI: 1.14-5.62), JAKi (OR, 2.64; 95% CrI: 1.26-5.99), and anti-IL-12/23 (OR, 3.15; 95% CrI: 1.01-13.35) were associated with increased risk of MACE when compared to placebo, while anti-IL-23 (OR, 2.65; 95% CrI: 0.85-10.03) was not associated with an increased risk of MACE (Table 1). The magnitude of the increased risk of MACE with different drug classes was not significantly different when compared by IMID type.
Discussion: In this meta-analysis, we found that JAKi, anti-TNF-α, and anti-IL-12/23 increased the risk of MACE, while anti-IL-23 did not. We did not find a differential risk of MACE when stratified by disease state. Larger prospective studies are needed to confirm these findings.
Figure: Figure 1: Network plot for occurrence of major adverse cardiovascular events according to drug class. Each node (circle) denotes a drug class. The node size is proportional to the total number of study patients assigned to each drug class. The line width (connection size) corresponds to the number of studies comparing the drug classes.
Shivani Mattay, MD1, Mohammad Zamani, MD2, Dany Saturno, MD3, Edward V.. Loftus, MD4, Matthew Ciorba, MD1, Andres Yarur, MD5, Siddharth Singh, MD6, Parakkal Deepak, MBBS, MS7. P2110 - Risk of Major Adverse Cardiovascular Events in Patients With Inflammatory Bowel Diseases or Other Immune-Mediated Inflammatory Disorders on Biologics and Small Molecules: A Systematic Review and Network Meta-Analysis, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.
