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      A Delphi Consensus Approach to Challenging Case Scenarios in Moderate-to-Severe Psoriasis: Part 1

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          Abstract

          Introduction

          Traditional clinical trials in psoriasis exclude a significant proportion of patients with complex disease and comorbidities. A consensus panel of 14 experts in the field of psoriasis was formed to conduct a Delphi method exercise to identify difficult-to-treat psoriasis clinical scenarios and to rank treatment approaches.

          Methods

          The exercise consisted of both survey questionnaires and a live meeting to review and discuss current data (as of 2009, when the exercise was conducted) and arrive at a consensus for optimal treatment options. Seventy difficult treatment scenarios were identified, and the top 24 were selected for discussion at the live meeting.

          Results

          Six of the 24 discussed case scenarios are presented in this article (another five are presented in Part 2): (1) psoriasis with human papilloma virus-induced cervical or anogenital dysplasia; (2) concomitant psoriasis and systemic lupus erythematosus; (3) severe psoriatic nail disease causing functional or emotional impairment; (4) psoriasis therapies that potentially reduce cardiovascular morbidity and mortality; (5) older patients (≥65 years of age) with psoriasis; and (6) severe scalp psoriasis that is unresponsive to topical therapy.

          Conclusion

          The Delphi exercise resulted in guidelines for practicing physicians to utilize when confronted with challenging patients with psoriasis.

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          Most cited references70

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          Polypharmacy in elderly patients.

          Polypharmacy (ie, the use of multiple medications and/or the administration of more medications than are clinically indicated, representing unnecessary drug use) is common among the elderly. The goal of this research was to provide a description of observational studies examining the epidemiology of polypharmacy and to review randomized controlled studies that have been published in the past 2 decades designed to reduce polypharmacy in older adults. Materials for this review were gathered from a search of the MEDLINE database (1986-June 2007) and International Pharmaceutical Abstracts (1986-June 2007) to identify articles in people aged >65 years. We used a combination of the following search terms: polypharmacy, multiple medications, polymedicine, elderly, geriatric, and aged. A manual search of the reference lists from identified articles and the authors' article files, book chapters, and recent reviews was conducted to identify additional articles. From these, the authors identified those studies that measured polypharmacy. The literature review found that polypharmacy continues to increase and is a known risk factor for important morbidity and mortality. There are few rigorously designed intervention studies that have been shown to reduce unnecessary polypharmacy in older adults. The literature review identified 5 articles, which are included here. All studies showed an improvement in polypharmacy. Many studies have found that various numbers of medications are associated with negative health outcomes, but more research is needed to further delineate the consequences associated with unnecessary drug use in elderly patients. Health care professionals should be aware of the risks and fully evaluate all medications at each patient visit to prevent polypharmacy from occurring.
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            A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis.

            Skin-infiltrating lymphocytes expressing type 1 cytokines have been linked to the pathophysiology of psoriasis. We evaluated the safety and efficacy of a human interleukin-12/23 monoclonal antibody in treating psoriasis. In this double-blind, placebo-controlled trial, 320 patients with moderate-to-severe plaque psoriasis underwent randomization to treatment with the interleukin-12/23 monoclonal antibody (one 45-mg dose, one 90-mg dose, four weekly 45-mg doses, or four weekly 90-mg doses) or placebo; 64 patients were randomly assigned to each group. Patients assigned to the interleukin-12/23 monoclonal antibody received one additional dose at week 16 if needed. Patients assigned to placebo crossed over to receive one 90-mg dose of interleukin-12/23 monoclonal antibody at week 20. There was at least 75% improvement in the psoriasis area-and-severity index at week 12 (the primary end point) in 52% of patients who received 45 mg of the interleukin-12/23 monoclonal antibody, in 59% of those who received 90 mg, in 67% of those who received four weekly 45-mg doses, and in 81% of those who received four weekly 90-mg doses, as compared with 2% of those who received placebo (P<0.001 for each comparison), and there was at least 90% improvement in 23%, 30%, 44%, and 52%, respectively, of patients who received the monoclonal antibody as compared with 2% of patients who received placebo (P<0.001 for each comparison). Adverse events occurred in 79% of patients treated with the interleukin-12/23 monoclonal antibody as compared with 72% of patients in the placebo group (P=0.19). Serious adverse events occurred in 4% of patients who received the monoclonal antibody and in 1% of those who received placebo (P=0.69). This study demonstrates the therapeutic efficacy of an interleukin-12/23 monoclonal antibody in psoriasis and provides further evidence of a role of the interleukin-12/23 p40 cytokines in the pathophysiology of psoriasis. Larger studies are needed to determine whether serious adverse events might limit the clinical usefulness of this new therapeutic target. (ClinicalTrials.gov number, NCT00320216 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Society.
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              Ustekinumab, a human interleukin 12/23 monoclonal antibody, for psoriatic arthritis: randomised, double-blind, placebo-controlled, crossover trial.

              Since some patients with psoriatic arthritis do not respond to typical drug treatments, alternatives are needed. Findings suggest that interleukins 12 and 23 might affect clinical symptoms and pathological joint changes of psoriatic arthritis. Ustekinumab is a human monoclonal antibody that inhibits receptor-binding of these cytokines. We aimed to assess the efficacy and safety of ustekinumab for psoriatic arthritis in this phase II study. We undertook a double-blind, randomised, placebo-controlled, crossover study at 24 sites in North America and Europe. Patients with active psoriatic arthritis were randomly allocated via interactive voice response system to either ustekinumab (90 mg or 63 mg) every week for 4 weeks (weeks 0-3) followed by placebo at weeks 12 and 16 (n=76; Group 1) or placebo (weeks 0-3) and ustekinumab (63 mg) at weeks 12 and 16 (n=70; Group 2). The first 12 weeks of the study were placebo-controlled. Masking was maintained to week 16, and patients were followed up to week 36 [corrected]. The primary endpoint was ACR20 response at week 12. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00267956. At week 12, 32 (42%) patients in Group 1 and ten (14%) in Group 2 achieved the primary endpoint (difference 28% [95% CI 14.0-41.6]; p=0.0002). Of 124 (85%) participants with psoriasis affecting 3% or more body surface area, 33 of 63 (52%) in Group 1 and three of 55 (5%) in Group 2 had a 75% or greater improvement in psoriasis area and severity index score at week 12 (47% [33.2-60.6]; p<0.0001). During the placebo-controlled period (weeks 0-12), adverse events arose in 46 (61%) patients in Group 1 and 44 (63%) in Group 2; serious adverse events were recorded in three (4%) Group 2 patients (none in Group 1). Ustekinumab significantly reduced signs and symptoms of psoriatic arthritis and diminished skin lesions compared with placebo, and the drug was well tolerated. Larger and longer term studies are needed to further characterise ustekinumab efficacy and safety for treatment of psoriatic arthritis.
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                Author and article information

                Contributors
                brucestrober30@me.com
                Journal
                Dermatol Ther (Heidelb)
                Dermatol Ther (Heidelb)
                Dermatology and Therapy : Research, Treatment and Aesthetic Interventions in Dermatology
                Springer Healthcare Communications (Heidelberg )
                2193-8210
                2190-9172
                17 March 2012
                17 March 2012
                December 2012
                : 2
                : 1
                : 1
                Affiliations
                [1 ]Department of Dermatology, University of Connecticut School of Medicine, Farmington, CT 06032 USA
                [2 ]Division of Dermatology, Department of Internal Medicine, Baylor University Medical Center, and Modern Dermatology, Dallas, TX USA
                [3 ]Department of Dermatology, NYU Langone Medical Center, New York, USA
                [4 ]Bakersfield Dermatology and Skin Cancer Medical Group, Bakersfield, CA USA
                [5 ]Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL USA
                [6 ]Department of Dermatology, Tufts Medical Center and Tufts University School of Medicine, Boston, MA USA
                [7 ]Division of Rheumatology, Allergy, and Immunology, Department of Medicine, University of California, San Diego, CA USA
                [8 ]Department of Dermatology, Case Western Reserve University School of Medicine, Cleveland, OH USA
                [9 ]Department of Dermatology, University of Utah, Salt Lake City, UT USA
                [10 ]Department of Dermatology, St. Louis University School of Medicine, St. Louis, MO USA
                [11 ]Department of Rheumatology, NYU Langone School of Medicine, New York, NY USA
                [12 ]University of Texas at Arlington, Graduate School of Nursing, and Modern Dermatology, Dallas, TX USA
                [13 ]Weill Medical College of Cornell University, Hospital for Special Surgery, New York Presbyterian Hospital, New York, NY USA
                Article
                1
                10.1007/s13555-012-0001-y
                3510391
                23205324
                f2826a10-3245-4d4a-a234-df0bb2e09daa
                © The Author(s) 2012
                History
                : 24 September 2011
                Categories
                Review
                Custom metadata
                © Springer Healthcare 2012

                Dermatology
                acitretin,biologics,methotrexate,psoriasis,psoriatic nail disease,severe scalp psoriasis,tnf-α inhibitor

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