Utilization of narrow-band ultraviolet light B Therapy and Etanercept for the Treatment of Psoriasis : efficacy, safety, and patient-reported outcomes

Journal of Drugs in Dermatology, March, 2008 by Leon Kircik, Jerry Bagel, Neil Korman, Alan Menter, Craig A. Elmets, John Koo, Yu-Ching Yang, Chiun-Fang Chiou, Frank Dann, Seth R. Stevens

Introduction

Psoriasis is a chronic, systemic, debilitating inflammatory disease involving the skin, and potentially the joints in patients with psoriatic arthritis. (1) It has an important impact on patient wellbeing, potentially resulting in embarrassment, self-consciousness, (2) and depression, (3) which may affect patients' social activities and work. (2,4,5)

An American Academy of Dermatology consensus statement recommends that patients with moderate to severe plaque psoriasis be treated with systemic therapy or phototherapy. (6) Traditionally, small molecule systemic therapies such as methotrexate and cyclosporine have been effective in treating moderate to severe plaque psoriasis, but these therapies may be associated with both short-term and long-term toxicities. Narrow-band (310-312 nm wavelength) ultraviolet light B (NB-UVB) phototherapy studies have shown significant clearing of skin lesions after a course of 20 treatments (3 times per week). (6-10) In another study, 62% of patients achieved at least 75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) after 12 weeks of UVB therapy. (11) Other than the average remission time induced, NB-UVB phototherapy is nearly as effective as psoralen-ultraviolet light A (PUVA) phototherapy, but is more convenient and has fewer adverse events. (12,13)

Targeted biologic therapies may offer some patients with effective treatment for their psoriasis, with fewer adverse effects than traditional systemic agents. (14-20) The fully human, soluble tumor necrosis factor (TNF) receptor, etanercept, has demonstrated efficacy in relieving the skin signs and symptoms and in improving health-related quality of life in patients with moderate to severe plaque psoriasis. (18-23) After 3 and 6 months of treatment, respectively, approximately 50% and 60% of patients in these trials experienced at least 75% improvement from baseline (PASI 75). Additionally, a recent publication reported that etanercept treatment was associated with improvement in the exploratory endpoints for fatigue and symptoms of depression. (21) Extensive clinical trial experience with etanercept has also demonstrated a favorable safety profile in this population. (24)

In clinical practice, it is recognized that in some patients, particularly those with recalcitrant disease, combination therapy may be required for optimal response. Topical steroids and phototherapy, in particular, have traditionally been used effectively to enhance the efficacy of other systemic treatments. (25) The reported efficacy of NB-UVB phototherapy may warrant use as an adjunct for systemic agents such as etanercept. The objectives of this open-label study were to evaluate the effectiveness, tolerability, and patient-reported outcomes of etanercept in combination with NB-UVB phototherapy for the treatment of moderate to severe psoriasis over a 12-week period.

Methods

Patients

Patients were enrolled from 16 sites in the United States and Canada. The institutional review boards of participating medical centers approved the protocol. Patients provided written informed consent to participate in the trial before any study procedures were conducted. To be eligible for study inclusion, patients had to be at least 18 years of age with stable active plaque psoriasis (PASI [greater than or equal to]15 and 25% of the individual plaques had to be considered severe) involving [greater than or equal to]5% of body surface area (BSA). Patients were excluded if they had received prior phototherapy; current or prior treatment with any TNF soluble receptor (etanercept) or monoclonal antibody (infliximab or adalimumab); other systemic therapies within 4 weeks of study initiation; topical corticosteroids, vitamin A or D analogues, or dithranol within 2 weeks of study initiation; or current or previous treatment with cyclophosphamide. Patients with the following conditions were also excluded: erythrodermic, pustular, or guttate psoriasis; skin conditions (eg, eczema) other than psoriasis that would interfere with study-related evaluations; active infection; history of immunocompromised health (eg, positive for human immunodeficiency virus); history of any cutaneous malignancy at any time; history of any noncutaneous malignancy within 5 years; actinic keratoses or atypical nevi; history of alcohol or drug abuse within 12 months of screening visit; evidence of photosensitivity disorder; severe comorbidities; current enrollment in a clinical trial or receipt of an investigational drug within 30 days of etanercept administration; or pregnancy.

Study Design

This multicenter, open-label, single-arm, prospective study (the Utilization of NB-UVB Light Therapy and Etanercept for the Treatment of Psoriasis [UNITE] study) evaluated the efficacy and safety of combination therapy with etanercept and NB-UVB phototherapy in patients with moderate to severe psoriasis. Patients could not receive PUVA phototherapy, broadband UVB therapy (including excimer laser), or use tanning booths or salons from the date of screening through the week 12 visit.