Risk of Major Adverse Cardiovascular Events and Thromboembolism Events in Patients with Psoriatic Arthritis on JAK Inhibitors

Objectives: Our objective was to evaluate the comparative effects of five Janus kinase inhibitors (JAKis) with ten interventions, comparing their impact on major adverse cardiovascular events (MACE) and thromboembolism events (TE) in patients with psoriatic arthritis (PsA) through network meta-analysis (NMA). Methods: We conducted a search across four databases from inception to September 30, 2024. We also included studies comparing JAKis with placebo or TNFi in adults (≥ 18 years) with PsA. The primary outcomes were the incidence of MACE and TE. We used network meta-analysis with random effects to estimate summary risk ratios (RRs). Results: Eleven studies met the eligibility criteria. Combined RCT and LTE data showed 23 MACE and 26 TE events, with incidence rates (IR) of 0.25 and 0.29 per 100 person-years for MACE and TE, respectively. Across all RCT data, there were 12 MACE and 8 TE events, with IRs of 0.62 and 0.41 per 100 person-years for MACE and TE, respectively. In eligible RCTs, tofacitinib (5 mg and 10 mg) and upadacitinib (30 mg) were associated with a lower risk of TE compared to placebo (GRADE certainty: moderate, moderate, and high, respectively). Compared to adalimumab, upadacitinib (15 mg and 30 mg) was associated with a decreased risk of MACE in RCT/LTE data (GRADE certainty: moderate and moderate, respectively). Conclusions: Tofacitinib and upadacitinib are superior to placebo and comparable to adalimumab regarding MACE and TE risk, even with long-term exposure, which may be positively considered in PsA treatment. The cardiovascular safety of new investigational JAKis needs further validation.