Rheumatoid arthritis patients with higher paraoxonase levels have lower MACE, cancer rates
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Key takeaways:
- Greater paraoxonase activity was associated with a lower risk for major adverse cardiovascular events in patients receiving tofacitinib.
- The researchers wrote that paraoxonase requires more investigation as a biomarker.
Patients receiving tofacitinib for rheumatoid arthritis with higher paraoxonase activity over time demonstrate a lower risk for major adverse cardiovascular events and malignancy, according to data published in the Journal of Rheumatology.
“Paraoxonase-1 (PON1) is a major high-density lipoprotein cholesterol (HDL-c)-associated enzyme synthesized mainly in the liver and secreted into the blood, where it associates predominantly with HDL-c,” Christina Charles-Schoeman, MD, MS, of the University of California Los Angeles, and colleagues wrote. “PON1 is considered to be atheroprotective and is implicated in cancer development, innate immunity, and bacterial quorum sensing.”
To examine the connection between PON1 and the risks for major adverse cardiovascular events (MACE) and malignancy in patients with RA receiving tofacitinib (Xeljanz, Pfizer), Charles-Schoeman and colleagues conducted a post hoc analysis of three phase 2 trials, six phase 3 studies and two long-term extension studies. All 11 studies were completed prior to Oct. 26, 2017. The analysis included patients who received one or more dose of tofacitinib 5 mg or 10 mg and had a measurement of PON1 activity available.
PON1 Q192R genotyping was performed, and disease activity and C-reactive protein scores were assessed, for all participants. Meanwhile, safety events of interest included MACE, inclusive of myocardial infarction, strokes and other cardiovascular events resulting in the death of the patient. The researchers also analyzed the prevalence of cancers not including non-melanoma skin cancers.
The analysis included a total of 1,969 patients with RA who received tofacitinib. According to the researchers, those who demonstrated an RR genotype, compared with a QQ genotype, demonstrated higher levels of paraoxonase activity, and lower levels of lactonase and arulesterase activity, at baseline (P < .001).
Following analysis through a time-varying models, the researchers additionally noted a “significant association” between increased paraoxonase activity over time and lower risks for MACE (P < .001) and malignancies excepting non-melanoma skin cancer (P .05), they wrote. These associations remained after controlling for potential risk factors.
“This post hoc analysis demonstrated that higher paraoxonase activity over time was associated with a significantly reduced risk of MACE and malignancies (excluding [non-melanoma skin cancer]) in tofacitinib-treated patients with moderate to severe RA,” Charles-Schoeman and colleagues wrote. “Further investigation of PON1 as a novel, functional lipid biomarker to assess MACE and malignancy risk in patients with RA is warranted.”
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