Ustekinumab Early Risk for Cardiovascular Events Save

JAMA Dermatology reports a claims-based, case-time-controlled French study of 9290 psoriasis patients suggesting that ustekinumab initiation may be associated with an increased risk of acute coronary syndrome or stroke in high risk cardiovascular patients.

Ustekinumab, an anti-interleukin 12/23p40 (IL-12/23p40) monoclonal antibody, is FDA approved for use in severe psoriasis, psoriatic arthritis, and Crohn disease.  The current study was undertaken as prior metaanalyses of IL-12/23 inhibitors (particularly briakinumab) suggesteda potential risk for major adverse cardiovascular events (MACE), especially in the first few months of treatment.  Yet there have been several studies and metanalyses that failed to show this association with ustekinumab.

Patients exposed to ustekinumab between April 2010 and December 2016, were classified by their cardiovascular risk factors into high- and low-risk groups.

Among 9290 exposed ustekinumab patients, 179 experienced a severe cardiovascular event (SCE) - 65 acute coronary syndrome, 68 unstable angina, and 46 with stroke. When comparing event rates according to cardiovascular risk category there were significantly more SSC in the high risk group:

• High CV risk: odds ratio, 4.17; 95% CI, 1.19-14.59L
• Low CV risk: odds ratio, 0.30; 95% CI, 0.03-3.13

This analysis suggests ustekinumab may trigger SCEs, primarily in high risk cardiovascular patients. The authors suggest a biologic plausibility wherein anti–IL-12/23p40 may be associated with atherosclerotic plaque destabilization mediated by Th17 T cells. 

It should be noted that there was no comparison of SCE rates in other psoriasis patients treated with other biologics or therapies and that psoriasis patients have a higher risk of cardiac events (much like rheumatoid arthritis).  Nonetheless, there is no warning or mention of cardiovascular risk in ustekinumab product labeling.