Secukinumab y disfunción endotelial en psoriasis

Journal of Investigative Dermatology

Impact of Secukinumab on Endothelial Dysfunction and Other Cardiovascular Disease Parameters in Psoriasis Patients Over 52 Weeks

J Invest Dermatol 2018 Nov 30;[EPub Ahead of Print], E von Stebut, K Reich, D Thaçi, W Koenig, A Pinter, A Körber, T Rassaf, A Waisman, V Mani, D Yates, J Frueh, C Sieder, N Melzer, NN Mehta, T Gori 

Psoriasis increases the risk of cardiovascular (CV) disease. Secukinumab, a fully human monoclonal antibody against IL-17A, shows significant efficacy in psoriasis, but effects on CV markers are unknown. CARIMA was a 52-week, randomized, double-blind, placebo-controlled, exploratory trial in patients with moderate to severe plaque psoriasis without clinical CV disease. Patients were randomized to 300 mg or 150 mg secukinumab until week 52, or placebo until week 12 then 300 mg or 150 mg secukinumab until week 52. The primary outcome was endothelial function measured by flow-mediated dilation (FMD). Baseline FMD was significantly lower in psoriasis patients than healthy volunteers (4.4±3.9% vs 6.1±3.3%, p=0.01). At week 12, baseline-adjusted mean FMD was numerically higher in patients receiving secukinumab vs. those receiving placebo, but this difference (300 mg group: +1.2%; 150 mg group: +0.76%; p=0.223 and p=0.403 by ANCOVA) did not reach significance. At week 52, FMD increased across groups. FMD was significantly higher than baseline in patients receiving the label dose of 300 mg secukinumab for 52 weeks (+2.1% [95% CI 0.8-3.3], p=0.0022). Other relevant CV markers were unchanged. CARIMA indicates that secukinumab might have a beneficial effect on CV risk by improving endothelial function of patients with plaque psoriasis.

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Mark G Lebwohl MD

IL-17 blockers have numerous benefits over TNF blockers for the treatment of psoriasis, at least in the short term. They have a high degree of safety without the black-box warnings concerning infection and malignancy that are in the package inserts of all of the TNF blockers. Moreover, they result in faster responses and greater efficacy than many of the TNF blockers. TNF blockers, however, have extensive registry evidence that they reduce myocardial infarctions in treated psoriasis patients, although attempts to demonstrate reductions in cardiovascular inflammation in patients treated with TNF blockers have been mixed.

Because IL-17 blockers are relatively new, it may take years for registries to demonstrate a reduction in cardiovascular events. Moreover, some studies suggest that IL-17 blockers are atherogenic, whereas others suggest that they are atheroprotective. Therefore, any study suggesting a cardiovascular benefit for anti–IL-17 therapy would be welcome.

Increased flow-mediated dilation has been associated with a reduction in cardiovascular risk; so, it was therefore selected as the primary endpoint in this ambitious study of 151 patients. Because cutaneous improvement occurs at week 12 with secukinumab, that time point was selected as the primary endpoint, but it was not until week 52 that significant increases in flow-mediated dilation were noted. There were no changes in arterial stiffness, plaque burden on MRI, or serum biomarkers for inflammation, although adiponectin was reduced in patients treated with secukinumab.

As with TNF blockers, definitive evidence that IL-17 blockers reduce cardiovascular inflammation by clearing psoriasis will require thousands of patients followed for years in registries. This study represents a solid first attempt to demonstrate reduction in cardiovascular inflammation, and, although it falls short, it does provide a hint of benefit if patients are followed long enough. More importantly, it suggests that future studies of cardiovascular inflammation look at later time points than week 12.

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 2224-0654
Momentum Escazu: 2101-9574

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