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The Effect of Upadacitinib on Lipid Profile and Cardiovascular Events: A Meta-Analysis of Randomized Controlled
Anastasios Makris1, Fotios Barkas2, Petros P Sfikakis3
1School of Medicine, European University Cyprus, Nicosia 2404, Cyprus.
Background:
Our aim was to systematically investigate the effect of upadacitinib, an oral JAK-1 selective inhibitor, on lipid profile and cardiovascular disease risk.
Methods:
PubMed, PubMed Central and ClinicalTrials.gov databases were searched for relevant randomized controlled trials (RCTs) up to 31 July 2022. We performed a qualitative synthesis of published RCTs to investigate the associations of upadacitinib with lipoprotein changes, along with a quantitative synthesis of MACE and mean lipoprotein changes where there were available data.
Results:
Nineteen RCTs were eligible for the present systematic review, which included 10,656 patients with a mean age of 51 years and a follow-up period of 12-52 weeks. Increases in low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were noted upon upadacitinib administration (3-48 mg/day) in 15 studies, while the LDL-C:HDL-C ratio remained unchanged. The pooled analyses of three placebo-controlled RCTs (n = 2577) demonstrated that upadacitinib at 15 mg increased the LDL-C by 15.18 mg/dL (95% CI: 7.77-22.59) and HDL-C by 7.89 mg/dL (95% CI: 7.08-8.69). According to the pooled analysis of 15 placebo-controlled RCTs (n = 7695), upadacitinib had no effect on MACE (risk ratio, RR: 0.62; 95% CI: 0.24-1.60). A sub-analysis focusing on upadacitinib at 15 mg (12 studies, n = 5395) demonstrated similar results (RR: 0.67; 95% CI: 0.19-2.36).
Conclusions:
Treatment with upadacitinib increases both LDL-C and HDL-C levels. Nevertheless, upadacitinib had no significant effect on the cardiovascular disease risk during a ≤52-week follow-up.
Insights
Upadacitinib increases LDL-C and HDL-C levels but does not significantly impact cardiovascular disease risk in studies up to 52 weeks. This systematic review examines lipid profiles and major adverse cardiovascular events (MACE).
Area of Science:
- Pharmacology
- Cardiovascular Medicine
- Rheumatology
Background:
- Upadacitinib is an oral JAK-1 selective inhibitor.
- Investigating its impact on lipid profile and cardiovascular disease risk is crucial.
Purpose of the Study:
- To systematically investigate the effect of upadacitinib on lipid profiles.
- To assess the association between upadacitinib and cardiovascular disease risk.
Main Methods:
- Systematic review and meta-analysis of randomized controlled trials (RCTs).
- Searched PubMed, PubMed Central, and ClinicalTrials.gov up to July 2022.
- Included qualitative synthesis of lipoprotein changes and quantitative synthesis of MACE and lipid changes.
Main Results:
- Nineteen RCTs with 10,656 patients were analyzed.
- Upadacitinib increased LDL-C and HDL-C levels, but the LDL-C:HDL-C ratio remained unchanged.
- No significant effect on MACE was observed (RR: 0.62; 95% CI: 0.24-1.60).
Conclusions:
- Upadacitinib treatment leads to elevations in both LDL-C and HDL-C.
- No significant increase in cardiovascular disease risk was detected within a 52-week follow-up period.
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