Hyperlipidaemic effect of Janus kinase inhibitors: a meta-analysis

Abstract

Introduction: Janus kinase (JAK) inhibitors are effective in treating rheumatoid arthritis. However, JAK is involved in lipid metabolism, so we investigated the association between JAK inhibitors and hyperlipidaemia. Methods: We conducted a literature search using ISI Web of Science, Scopus, Medline, Cochrane library, Clinicaltrials.gov, and Embase. We included randomised controlled trials reporting the frequency of hypercholesterolaemia or hyperlipidaemia as a study outcome. Results were analysed using RevMan 5.3.5. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a random effects model. The standardised mean differences (SMDs) and 95% CIs were estimated for the change in lipid profile. Results: In all, 17 trials were included in the meta-analysis. Janus kinase inhibitors were associated with hypercholesterolaemia (OR=2.52, 95% CI=1.59-3.99; I2 statistics: 0%) and hyperlipidaemia (OR=3.23, 95% CI=1.73-6.04; I2 statistics: 0%). Both JAK inhibitors were associated with increase in serum high-density lipoprotein level (baricitinib: SMD=1.60, 95% CI=0.67-2.53 mg/dL; tofacitinib: SMD=2.80, 95% CI=0.61-4.98 mg/dL) and low-density lipoprotein level (baricitinib: SMD=2.47, 95% CI=0.40-4.53 mg/dL; tofacitinib: SMD=2.79, 95% CI=1.17-4.41 mg/dL). Conclusions: Janus kinase inhibitors increased serum low-density lipoprotein and high-density lipoprotein levels. Significant associations between JAK inhibitors and hypercholesterolaemia as well as hyperlipidaemia were revealed. If causal, there would be important clinical implications for rheumatoid arthritis patients.