Association Between the Type and Length of Tumor Necrosis Factor Inhibitor Therapy and Myocardial Infarction Risk in Patients With Psoriasis

August 2013 | Volume 12 | Issue 8 | Original Article | 899 | Copyright © August 2013


Jashin J. Wu MD,a Kwun-Yee T. Poon MS,b and Judith D. Bebchuk ScDb

aDepartment of Dermatology, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA
bDepartment of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA

Abstract
OBJECTIVE: We sought to assess whether the type of TNF inhibitor therapy (soluble receptor versus monoclonal antibody) has an effect on MI risk; and determine whether length of TNF inhibitor therapy has an effect on MI risk.
DESIGN: Retrospective cohort study
SETTING: Between January 1, 2004 and November 30, 2010
PARTICIPANTS: At least 3 ICD9 codes for psoriasis (696.1) or psoriatic arthritis (696.0) (without antecedent MI).
INTERVENTION: None
MAIN OUTCOME MEASURE: Incident MI
RESULTS: In the 3 subgroups of TNF inhibitors, 976 received etanercept; 217 received monoclonal antibody; and 480 received etanercept or monoclonal antibody, in addition, 5075 received topical therapy and 2097 received oral therapy. In the Cox proportional hazards analysis, etanercept (HR, 0.53; 95% CI, 0.31-0.92) was associated with a significant reduction of MI risk, compared to topical agents and, monoclonal antibody only (HR, 0.25; 95% CI, 0.06-1.03), and etanercept or monoclonal antibody (HR, 0.53; 95% CI, 0.27-1.06) were associated with a non-significant reduction of MI risk compared to topical agents. Using year 1 as reference, those who received TNF inhibitor therapy at year 2 (HR, 1.15; 95% CI, 0.30-4.44), at year 3 (HR, 1.89; 95% CI, 0.64-5.58), and at year 4 and above (HR, 1.16; 95% CI, 0.46-2.94) had a non-significant increase of MI risk.
CONCLUSIONS: Treatment with etanercept, compared to treatment with topical agents, was associated with a significant decreased risk of MI in psoriasis patients. Treatment with monoclonal antibody and etanercept or monoclonal antibody, compared to treatment with topical agents, was associated with a non-significant decreased risk of MI risk in psoriasis patients. There were no statistically significant changes in risk of MI associated with length of TNF inhibitor treatment.

J Drugs Dermatol. 2013;12(8):899-903.

INTRODUCTION

Psoriasis is an inflammatory skin condition affecting approximately 2-3% of the United States and world populations.1, 2 It is a systemic inflammatory state that is associated with an increased risk of cardiovascular diseases, including atherosclerosis,3-5 diabetes type 2,6, 7 dyslipidemia,8, 9 hypertension,6, 9 obesity,8, 10 metabolic syndrome,2, 11peripheral vascular disease,10 coronary artery calcification,12 myocardial infarction (MI),9, 13 stroke,9, 14 and cardiac death.15, 16
Tumor necrosis factor (TNF) inhibitor therapy has shown efficacy for psoriasis and psoriatic arthritis.17-20 Within the TNF inhibitor drug class, they may be categorized as the soluble TNF receptor therapy etanercept and the monoclonal antibodies such as adalimumab and infliximab.
Our group has recently published a study where the use of TNF inhibitors for psoriasis was associated with a statistically and clinically significant reduction of MI risk and incidence rate for MI when compared to those treated with topical agents.21 The use of TNF inhibitors for psoriasis was associated with a smaller incidence rate for MI than psoriasis patients treated with oral/phototherapy although the rates were not statistically different.21
For this follow-up analysis of the above study, the study objective was to determine whether the type of TNF inhibitor therapy (soluble receptor versus monoclonal antibody) has an effect on the risk of MI. Another study objective was to determine whether length of TNF inhibitor therapy has an effect on the risk of MI.

METHODS

Study Setting

This was a retrospective cohort study conducted within the Kaiser Permanente Southern California (KPSC) Health Plan, a large integrated health maintenance organization that served approximately 3.3 million members as of December 31, 2011. Membership demographics, racial/ethnic, and socioeconomic status composition are representative of California, and the plan serves about 15% of the region’s population. More than 92% of