Frequency of Thrombocytopenia in Psoriasis Patients Treated With Tumor Necrosis Factor-α Inhibitors

March 2011 | Volume 10 | Issue 3 | Original Article | 280 | Copyright © March 2011


Meng Chen MD, Michael J. Holland MD, Mohsin R. Mir MD, Michael G.Wong BA, Brian P. Kelley MD, Kelli D. Grim MD, Sunaina S. Bhuchar MD, Sylvia Hsu MD

Department of Dermatology, Baylor College of Medicine, Houston, TX

Abstract
Tumor necrosis factor-α (TNF-α) inhibitors are biologic agents that are currently in wide use for the treatment of psoriasis as well as other inflammatory diseases. Following reports of thrombocytopenia as a potential adverse effect of anti-TNF-α therapy, we performed a retrospective study to determine the frequency of thrombocytopenia, defined as a platelet count <50x109 cells/L, in a cohort of 187 psoriatic patients treated with anti-TNF-α agents over a nine-year period. Although none of our patients met serologic criteria for thrombocytopenia or displayed clinical manifestations of thrombocytopenia, two patients developed platelet counts below 100×109 cells/L. Thrombocytopenia induced by anti-TNF-α agents is a potential adverse effect, it is a rare occurrence that will require further investigation in large, placebo-controlled, double-blind, prospective studies.

J Drugs Dermatol. 2011;10(3):280-284.

INTRODUCTION

Psoriasis is a chronic, often lifelong inflammatory skin disease that affects as many as 7.5 million Americans and 125 million people worldwide.1 Traditional treatments, such as topical applications, phototherapy, methotrexate, and cyclosporine have the potential to be ineffective, inconvenient or toxic after long-term use.2 Improvements in the understanding of the pathogenesis of psoriasis have allowed for the development of treatment strategies that act on specific components of the immune system.2 As tumor necrosis factor-α (TNF-α ) plays a key role in the etiopathogenesis of psoriasis, anti-TNF-α biologic agents are now used increasingly as an effective, longterm treatment of psoriasis.3
However, there have been some concerns regarding the safety of anti-TNF-α agents. Anti-TNF-α agents have recently been reported to induce thrombocytopenia. Reports of this adverse event had been sporadic until a retrospective, observational study of 93 patients by Brunasso et al. reported a 5.97 percent (4 of 67 patients, 95% CI, 0% to 8.59%) rate of thrombocytopenia occurrence among their cohort of patients receiving anti-TNF-α agents for psoriasis and psoriatic arthritis.4
The anti-TNF-α biologic drugs that are currently approved by the U.S. Food and Drug Administration (FDA) include three agents that are unique in structure, development and mechanism.
Etanercept is a recombinant human TNF-α receptor protein fused with the FC portion of IgG1 and adalimumab is a fully human anti-TNF-α monoclonal antibody.2 Infliximab is a chimeric mouse-derived monoclonal IgG1 antibody with human constant and murine variable components.5
A fourth biologic agent not of the anti-TNF-α class, efalizumab, was also included in the study by Brunasso et al. It is a recombinant monoclonal antibody targeting the CD11a subunit of the lymphocyte function-associated antigen 1 (LFA-1) integrin that mediates T-cell adhesion.2 Efalizumab was withdrawn from the worldwide market in 2009 due to reports of progressive multifocal leukoencephalopathy in long-term users of the drug.
The present study was conducted to evaluate the frequency of thrombocytopenia among psoriasis patients treated with any of the three anti-TNF-α agents. We sought to expand on the findings by Brunasso et al. and to substantiate or refute the reported rate of thrombocytopenia related to the use of anti- TNF-α drugs for psoriasis in a larger patient group.

METHODS

A retrospective chart review was performed of 187 psoriatic patients (male:female=93:94; mean age 47; median age 40; range 18–76) treated with anti-TNF-α agents at the Adult Dermatology Clinic, Baylor College of Medicine, Houston, Texas during the period from December 2000 to November 2009.
Among all patients, 143 had received adalimumab, 81 had received infliximab, and 43 had received etanercept. Of the 187 patients, 126 had received only one anti-TNF-α agent, 47 had received two anti-TNF-α agents, and 14 had received all three anti-TNF-α agents over the course of their treatment. Thirteen