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ICYMI: ORAL Surveillance - Is Statin Use the Problem/Solution?

The findings from ORAL Surveillance Study have been a dominant conversation at recent ACR Convergence, with the seminal findings and subsequent analyses a target of debate. This study comparing the safety of tofacitinib (initially designed as 5 and 10 mg twice daily) versus TNF inhibitors was critical in its finding that tofacitinib was not non-inferior to TNF inhibitor in major adverse cardiovascular events (MACE). This finding prompted safety concern amongst rheumatology providers and patients, leading to a FDA warning across all JAK inhibitors. Subsequent post-hoc analyses, follow-up studies, and claims data analyses have been used to further interpret the data, though a clear answer on safety is not certain.

On Sunday November 17, 2024 at ACR Convergence, Dr. John Giles of Cedars Sinai Medical Center reported on a new post-hoc analysis that provides new insights (abstract 1745).

His research focuses on the statin usage in the patient population and its effect on MACE events. In the study, only 23.4% of the patient population was on a statin medication, despite the fact that this study was enriched for cardiovascular risk. Amongst patients with a known history of atherosclerotic cardiovascular disease (ASCVD), only 53% were treated with statins at baseline and only 14.1% were on a high intensity statin. Though baseline statin usage was similar in tofacinitib and TNFi treated groups, there was more patients started on a statin in tofacinitib group (11.8% for 5 mg BID; 12.2% for 10 mg BID) versus TNFi (6.7%).

The next aim of the study was to look at the effect that statins had on the study patients' lipid leels. Baseline LDL and LDL:HDL ratio were lower in patients on statin therapy. Tofacitinib was noted to increase LDL and HDL from baseline more than TNFi therapy, but this increase was attenuated with statin therapy.

The final goal was evaluating the impact of statin usage on MACE. Dr. Giles presented that tofacitinib-treated patients with ASCVD history had lower MACE occurrence with statin treatment compared to those without statin use (Hazard ratio 0.49, 95% CI 0.25, 0.95). This pattern was not seen in TNFi-treated patients with ASCVD history. Though MACE events were higher in the tofacinitib patients off statins compared to TNFi off statins (HR 4.07, CI 1.20, 13.82), this difference was not seen with statin usage. When studying patients with ASCVD history and statin usage, there was no difference in incident MACE (HR 1.17, CI 0.48, 3.0).

The most glaring takeaway from this study is the clear deficiency in prevention in these patients. Statin usage is essential for primary or secondary prevention of MACE and these patients were not optimally treated at goal with inadequate usage and dosing of statin therapy. Statins have been shown to clearly improve lipid levels and decrease MACE risk. This study's data suggests that improving statin therapy may mitigate much of the MACE concerns in JAK inhibition. In patients with ASCVD, tofacitinib and JAK inhibitors should be used with caution, particularly if other co-morbidities are present, but managing risk appropriately with all preventative measures (including statin usage, weight loss, smoking cessation, blood pressure management) can help improve safety overall.

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James Dowd

| Dec 13, 2024 12:00 pm

What is the NNT for statins? 40, 80 150? Depends on risk. Would you take MTX, aTNF for your RA if the NNT was 40 or higher? Now ask what is the NNH for statins? The same as the NNT? Why do we rx these things? Pharma influenced data? I won't prescribe these or take them. I will focus on diet first.

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