Cardiovascular risk and safety profile of Janus Kinase inhibitors in axial spondiloarthritis: a meta-analysis of randomized clinical trials.

Abstract

Background: Janus kinase inhibitors (iJAKs) have emerged as a therapeutic option for axial spondyloarthritis (axSpA), but their cardiovascular (CV) risk and safety profile remain under investigation. Objectives: Evaluate the CV and safety outcomes of iJAKs in patients with axSpA through a meta-analysis of randomized controlled trials (RCTs). Methods: PubMed, Embase, and the Cochrane Database were conducted to identify RCTs comparing iJAKs with placebo in axSpA. Outcomes included any adverse events (AEs), severe AEs (SAEs), discontinuation due to AEs, major adverse cardiovascular events (MACE), venous thromboembolism (VTE), serious infections of COVID-19 and herpes zoster. Odds ratios (OR) with 95% confidence intervals (CI) were pooled using a fixed-effects model. Heterogeneity was assessed using I² statistics. Results: Six RCTs involving 1,618 patients were included. iJAKs did not significantly increase the risk of any AEs (OR 1.16; 95% CI 0.94–1.43; p=0.16), SAEs (OR 1.77; 95% CI 0.93–3.36; p=0.08), or discontinuation due to AEs (OR 1.12; 95% CI 0.62–2.03; p=0.70). No MACE events were reported in either group. The risk of VTE was comparable between iJAKs and placebo (OR 1.01; 95% CI 0.23–4.46; p=0.99). However, iJAKs were associated with a higher risk of serious infections of COVID-19 (OR 6.43; 95% CI 1.14–36.14; p=0.03) and herpes zoster (OR 5.11; 95% CI 1.11–23.44; p=0.04). Conclusion: In patients with axSpA, iJAKs demonstrated a comparable CV safety profile to placebo but were associated with an increased risk of serious infections of COVID-19 and herpes zoster. These findings highlight the need for careful monitoring of infections in iJAK-treated patients. Keywords: Janus kinase inhibitors; axial spondyloarthritis; cardiovascular risk; safety; meta-analysis.