Ustekinumab Treatment for Psoriasis in 119 Patients Maintained on Therapy for a Minimum of One Year: A Review

August 2014 | Volume 13 | Issue 8 | Original Article | 905 | Copyright © 2014

Elizabeth G. Wilder MD,a Mahir Patel MD,a Katherine Hebeler BA,b and Alan Menter MDa

aDivision of Dermatology, Baylor University Medical Center, Dallas, TX
bWashington University, St. Louis, MO

Abstract

Ustekinumab is a human IgG1κ monoclonal antibody that binds with high affinity and specificity to the p40 protein subunit shared by both the interleukin-12 and interleukin-23 cytokines. This study reviews clinical response and adverse events in 119 psoriasis patients who have received ustekinumab for a minimum of 1 year. The medical records of 119 psoriasis patients treated with ustekinumab at our referral clinic in Dallas between 2009 and 2013 were reviewed for response rates, side effects, and concomitant therapies. Of 119 patients, 117 (98%) had plaque type psoriasis, with 40 (34%) patients having psoriasis affecting either their palms and/or soles. Forty-four (37%) patients had psoriatic arthritis. The median follow-up period was 31 months. Fifty-six (47%) of the 119 patients obtained near complete clearance (response of more than 90% of initial body surface area involvement) upon the final follow-up visit or at the time of ustekinumab treatment discontinuation. Concomitant systemic treatments, primarily methotrexate, were given to 59 (50%) patients. Twenty-three (19%) patients discontinued treatment, primarily for sub-optimal response or loss of response. Fifty (42%) patients required either an increase in the dose of ustekinumab to 90 mg and/or administration more frequently than every 12 weeks to achieve and maintain psoriasis clearance.

J Drugs Dermatol. 2014;13(8):905-910.

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INTRODUCTION

Psoriasis is a chronic and complex genetic immune-mediated disease affecting up to 2% of the US population.1 The pathogenesis of psoriasis stems from dysregulated inflammation, which leads to hyperproliferation of the basal keratinocytes and incomplete differentiation of the epidermis. The disease process is perpetuated by infiltration of helper T cells 1 (Th1) and helper T cells 17 (Th17), dermal dendritic cells, Langerhans cells, and neutrophils with altered levels of chemokines and integrins.1,2

Biologic agents are widely used treatments for moderate to severe chronic plaque psoriasis and they target specific components of the immunologic pathway. While tumor necrosis factor-α (TNF-α) inhibitors have been available for treatment in psoriasis for more than 10 years, ustekinumab is the only monoclonal antibody specifically targeting interleukin-12 (IL-12) and interleukin-23 (IL-23) that is currently approved by the US Food and Drug Administration (FDA).2,3

Both IL-12 and IL-23 are involved in the differentiation of naïve T cells into Th cells. Th1 cells develop from naïve T cells after exposure to IL-12, whereas IL-23 stimulates proliferation of Th17 cells. These Th cells each express unique cytokines, some of which are proinflammatory cytokines that are further involved in the immune response and subsequent systemic inflammation. Both IL-12 and IL-23 share a common p40 subunit, which is overexpressed in psoriatic plaques.4

Ustekinumab is a human IgG1κ monoclonal antibody that binds with high affinity and specificity to the p40 protein subunit shared by both the IL-12 and IL-23 cytokines.5 Three phase 3 clinical trials have shown that ustekinumab produces a rapid improvement in the majority of patients with moderate to severe plaque psoriasis. 6,7,8 The European Medicines Agency (EMA) approved the use of ustekinumab for moderate to severe plaque psoriasis in January 2009, and the FDA in September 2009.4 In September 2013 they both approved ustekinumab for the treatment of moderateto- severe psoriatic arthritis in adult patients.

Five-year safety data have recently been published on patients exposed to ustekinumab.4,5,9 These data were pooled from 4 studies of ustekinumab for psoriasis with analysis of 3,117 patients who received at least 1 dose of ustekinumab, with 1,482 patients treated for 4 or more years and 838 patients treated for 5 or more years. Rates of adverse events (AEs), serious AEs, infections, nonmelanoma skin cancers, other malignancies, and major cardiac AEs were analyzed by dose and year of exposure. Rates of overall mortality and other malignancies were comparable with those expected in the general US population, and no dose-related or cumulative toxicity was observed with continued exposure to ustekinumab for up to 5 years.4,5,9 Rates of AEs reported in ustekinumab psoriasis trials are generally comparable with those reported for other biologics approved for the treatment of moderate-to-severe psoriasis.10

Since its approval in September 2009, our psoriasis specialty clinic has prescribed ustekinumab for psoriasis treatment to over 450 patients. We conducted a retrospective analysis of patients treated

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