JAK inhibitors may increase cholesterol in people with RA
medwireNews: Treatment with any of the five Janus kinase (JAK) inhibitors approved for use in rheumatoid arthritis (RA) in the USA, Europe, or Japan may lead to an increase in serum cholesterol levels, suggest results of a systematic review and network meta-analysis.
Ping Feng and colleagues from Sichuan University in Chengdu, China, found that both low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol levels increase after treatment with a JAK inhibitor.
Their study included data from 18 phase 2 and 3 randomized controlled trials involving baricitinib (n=6), peficitinib (n=5), tofacitinib (n=3), upadacitinib (n=2), or filgotinib (n=2). In total, 3341 patients were given a JAK inhibitor and 3356 received placebo or an active comparator.
Feng and team report in Clinical Rheumatology that HDL cholesterol levels increased by a mean of 8.11 mg/dL from baseline while LDL cholesterol levels increased by a mean of 11.37 mg/dL from baseline in a pooled analysis of all people receiving a JAK inhibitor.
The greatest mean increase in HDL cholesterol levels occurred after treatment with peficitinib (10.77 mg/dL), followed by baricitinib (7.99 mg/dL), upadacitinib (6.78 mg/dL), tofacitinib (6.69 mg/dL), and filgotinib (6.03 mg/dL).
For LDL cholesterol levels, the highest mean increase occurred after upadacitinib use (17.22 mg/dL), followed by tofacitinib (13.51 mg/dL), baricitinib (13.48 mg/dL), filgotinib (7.47 mg/dL), and peficitinib (6.62 mg/dL).
The researchers then calculated the comparative effects of JAK inhibitors on HDL and LDL cholesterol levels and found that there were generally no significant differences between each of the treatments. The only exception was that the increase in LDL cholesterol levels was significantly lower with peficitinib than with upadacitinib.
In addition, the increase in HDL cholesterol levels from baseline was significantly greater in people who received baricitinib, filgotinib, peficitinib, or tofacitinib relative to those on placebo, while increases in LDL cholesterol levels were significantly greater in those taking any of the five JAK inhibitors versus placebo.
Despite the increased serum cholesterol levels, Feng et al found that there was no significant increase in the risk for cardiovascular disease with JAK inhibitor use overall or with each of the agents individually.
Nonetheless, they conclude: “Further long-term research is required to gain a better understanding of the consequences of elevated lipid levels in RA patients and the effects of different JAK inhibitors on cholesterol metabolism.”
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