Evaluation of Risk of Major Adverse Cardiovascular Events With Biologic Therapy in Patients With Psoriasis

October 2017 | Volume 16 | Issue 10 | Original Article | 1002 | Copyright © October 2017

Robert Bissonnette MD,a Francisco Kerdel MD,b Luigi Naldi MD,c Kim Papp MD,d Claudia Galindo MD,e Wayne Langholff PhD,f K. L. Tang PhD,f Philippe Szapary MD MSCE,f Steven Fakharzadeh MD PhD,e Bhaskar Srivastava MD PhD,e Kavitha Goyal MD,e and Alice B. Gottlieb MD PhDg

aInnovaderm Research, Inc., Montreal, Quebec, Canada bFlorida Academic Dermatology Centers, Miami, FL cCentro Studi GISED, Ospendali Riuniti, Bergamo, Italy dK. Papp Clinical Research and Probity Research, Waterloo, Ontario, Canada eJanssen Scientific Affairs, LLC., Horsham, PA fJanssen Research & Development, LLC, Spring House, PA gDepartment of Dermatology, New York Medical College, Valhalla, NY

BACKGROUND: Psoriasis is associated with increased risk of major adverse cardiovascular events (MACE). OBJECTIVES: Compare MACE risk with biologics vs topical/phototherapy use. METHODS: Psoriasis Longitudinal Assessment Registry (PSOLAR) is an international psoriasis registry of patients eligible to receive biologic/systemic treatments prospectively. MACE is defined as myocardial infarction, stroke, or cardiovascular death. Biologic cohorts, including tumor necrosis factor-alpha (TNF-α) inhibitors (ie, adalimumab, etanercept, and infliximab) and ustekinumab, combined and by class, were compared with a topical/phototherapy cohort. Incidence rates of MACE per 100-patient-years (100PY) with 95% confidence intervals (95% CI) are reported. Multivariate analyses were performed to evaluate the effect of treatment on the risk of MACE adjusting for confounders. RESULTS: Analyses included 7550 patients: 6767 in the combined biologics cohort (3949 and 2818 in the TNF-α inhibitors and ustekinumab cohorts, respectively) and 783 in the topical/phototherapy cohort. Mean duration of exposure was approximately 2.8 years (combined biologics) and 4.1 years (topical/phototherapy). A total of 52 MACE were reported; MACE incidence rates were 0.22/100PY (95% CI: 0.16, 0.30) for the combined biologics cohort (TNF-α inhibitors [0.20/100PY (0.12, 0.31)] and ustekinumab [0.24/100PY (0.15, 0.37]) and 0.34/100PY (0.17, 0.61) for the topical/phototherapy cohort. For the combined biologics (hazard ratio=0.92; 95% CI [0.426, 1.988]), TNF-α inhibitor (0.85 [0.373, 1.928]), and ustekinumab (1.03[0.440, 2.402]) cohorts, treatment was not associated with increased risk of MACE versus the topical/phototherapy cohort. CONCLUSION: Based on data accumulated to date in PSOLAR, treatment with biologics did not have an impact on the risk of MACE in patients with moderate-to-severe psoriasis.

J Drugs Dermatol. 2017;16 (10):1002-1013.


Psoriasis has been associated with an increased risk of cardiovascular (CV) disease and risk factors, especially among patients with severe disease.1 Patients with psoriasis may have an increased risk of major adverse cardiovascular events (MACE; defined as myocardial infarction [MI], stroke, and CV death).2,3 Biologic therapies are increasingly used to treat moderate-to-severe psoriasis. As psoriasis is a chronic disease requiring long-term treatment, understanding any potential impact of biologic therapy on MACE is valuable for clinical decision making. Results from clinical studies for approved tumor necrosis factor-alpha (TNF-α)4-7 and interleukin (IL)-12/23 inhibitors8-10 demonstrated that these therapies generally do not increase the risk of adverse cardiovascular outcomes. A possible MACE association was noted in the Phase 2 ustekinumab psoriasis study;11 however, was not observed in subsequent Phase 3 ustekinumab psoriasis studies, including long-term followup.8-10 Observational studies based on larger numbers of patients have analyzed the effect of psoriasis therapies on CV disease, yet the findings are not consistent; some studies reported benefit12-14 and others reported no effect.15-17 Psoriasis Longitudinal Assessment Registry (PSOLAR) is an international, longitudinal, observational, disease-based registry that prospectively follows patients with psoriasis eligible to receive biologic and/or conventional systemic therapies.18,19 PSOLAR was designed to capture long-term safety data and clinical outcomes for more than 12,000 patients with psoriasis. Previous analyses from PSOLAR based on methods for safety surveillance