NEW ORLEANS – The use of tumor necrosis factor inhibitors in psoriasis patients is independently associated with nearly a 50% reduction in MI risk compared with that of patients not on the biologic agents, a large retrospective cohort study has shown.
In this study of 24,081 psoriasis patients belonging to Kaiser Permanente Southern California, those on TNF inhibitors had an adjusted 48% reduction in the risk of MI during 4 years of follow-up, compared with patients on other therapies. This was the case in a multivariate analysis controlling for traditional cardiovascular risk factors as well as use of statins, beta-blockers, and other medications known to reduce cardiovascular risk, Dr. Jashin J. Wu reported at the annual meeting of the American Academy of Dermatology.
Previous studies by other investigators have shown that psoriasis is associated with an increased cardiovascular event rate, and that the risk is greatest in those patients having severe skin disease. But in the Kaiser Permanente study, patients on TNF inhibitors had a 44% lower MI risk than patients with mild psoriasis in the multivariate analysis, noted Dr. Wu, a dermatologist at Kaiser Permanente Los Angeles Medical Center.
At baseline, more than half of all the Kaiser psoriasis patients had dyslipidemia, more than half were hypertensive, and 22% had type 2 diabetes. Fully 48% of the 1,877 patients on TNF inhibitors had psoriatic arthritis, as did 21.5% of patients on methotrexate or other oral drugs or phototherapy, and 2.9% of those with mild psoriasis not on these other therapies.
In the multivariate analysis, psoriatic arthritis was independently associated with a 58% increased risk for MI compared with that of psoriasis patients without joint symptoms.
There were 26 MIs in the TNF inhibitor group, 54 in those on oral agents or phototherapy, and 397 in patients with mild psoriasis. This translated into an MI incidence of 268 cases per 100,000 person-years in patients on TNF inhibitors, 373/100,000 in those on oral therapy or phototherapy, and 481/100,000 person-years in patients with mild psoriasis.
Methotrexate has previously been shown to reduce cardiovascular risk. Of note, in this study the use of TNF inhibitors was associated with a significant 41% reduction in MI risk compared with that of methotrexate-treated patients.
Dr. Wu said the likely mechanism of benefit for anti-TNF therapy in terms of reduced MIs in psoriasis patients involves the marked reduction in systemic inflammation achieved with these agents. He noted that etanercept, the most prescribed TNF inhibitor in the Kaiser cohort, has been shown to reduce the elevated C-reactive protein levels present in patients with moderate to severe psoriasis (Br. J. Dermatol. 2008; 159:322-30).
Because of its retrospective nature, the Kaiser study doesn’t prove causality, Dr. Wu observed. But he added that the results do raise several intriguing questions. For example, if the reduced risk of MI with anti-TNF therapy seen in this large study is real, does the use of these agents in psoriasis patients also reduce their risk of other cardiovascular end points, such as stroke, heart failure, and cardiac death? And do the various TNF inhibitors vary in the degree of cardiovascular risk protection they provide?
The Kaiser study is ongoing, with continuing patient enrollment and follow-up, and further reports are expected in the future.
Dr. Wu disclosed that he has received research funds from Abbott Laboratories and Amgen; however, the Kaiser psoriasis project is wholly funded by Kaiser Permanente.