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Alefacept in combination with tapering doses of methotrexate in patients with psoriasis1
P586
P588
CLASS I TOPICAL CORTICOSTEROID USE FOR PSORIASIS PATIENTS IN AN ACADEMIC PRACTICE Dan Pearce, MD, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, United States, Alan Fleischer, Jr., MD, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, United States, Steven Feldman, MD, PhD, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, United States Background: Psoriasis is a chronic skin disorder that can have profound QOL implications for patients. For the clinician, the treatment of psoriasis is complicated by the availability of numerous topical agents, systemic agents, as well as phototherapy. Of the topical preparations available, the ultra-high potency corticosteroids, or Class I steroids, have an important role in treating psoriasis in a wide spectrum of disease. Purpose: The purpose of this study was to examine the prescribing patterns of ultra-high potency, or Class I, topical steroids in patients with various types of psoriasis. Methods: A retrospective chart review of greater that 500 patients with psoriasis from an academic dermatology practice was performed. Class I steroid use was defined as those patients that were observed to be currently using Clobetasol, Halobetasol, Augmented Betamethasone Results: 79% of patients in our sample were prescribed topical steroids of any class while 46% of patients were prescribed a Class I steroid. Thus, greater than 58% of patients receiving topical steroid therapy received a Class I agent. 11% of patient’s prescribed class I steroids were also receiving systemic therapy for their psoriasis. Conversely, 35% of patients who were receiving systemic therapy were also receiving Class I topicals. Discussion: The use of Class I topical steroids is fairly commonplace, even among patients on systemic therapy for severe psoriasis. These ultra-high potency topicals provide a relatively safe adjunct to systemic therapy and remain a mainstay of psoriasis therapy.
LONG-TERM USE OF INTRAVENOUS ALEFACEPT: SAFETY AND OFF-TREATMENT RESPONSES IN PATIENTS WHO HAVE RECEIVED FOUR OR MORE COURSES OF THERAPY Alan Menter, MD, Texas Dermatology Associates, Dallas, TX, United States, Jennifer Cather, Texas Dermatology Associates, Dallas, TX, United States Psoriasis is a chronic disease that often requires repeated courses of treatment to maintain satisfactory control of disease signs and symptoms. Alefacept is a fully human LFA-3/IgG1 fusion protein that inhibits T-cell activation and stimulates apoptosis of memory (CD45RO⫹) T cells, which have been implicated in psoriasis pathogenesis. Alefacept is the first biologic agent approved for the treatment of adult patients with chronic plaque psoriasis. The safety and efficacy of alefacept, administered as a once weekly injection (either intravenous [IV] bolus or intramuscular) for 12 weeks followed by a 12-week observation period, are well documented for 1 and 2 courses of therapy. As part of the clinical development program, patients who completed phase 2 studies were eligible to participate in an open-label extension study to determine the safety and efficacy of repeated courses of alefacept. The drug was administered at a fixed dose of 7.5 mg by 30-second IV bolus once weekly for 12 weeks followed by a 12-week observation period. Subjects may receive repeated courses of alefacept if their psoriasis recurs 12 weeks or more after therapy is completed and their CD4⫹ T-cell count is at or above the lower limit of normal. Efficacy is assessed by the percentage of responders (as measured by PASI score and physician global assessment), the duration of response from course to course, the time to retreatment, and the reasons for attrition from the study. Adverse events, including infection and malignancy rates, and clinical laboratory data are collected weekly during therapy and for 12 weeks after each course. This is an ongoing trial. Data through 3 courses of therapy have been previously presented and published (Lowe NJ, et al. Int J Dermatol 2003;42:224-230). Some patients have now received up to 8 courses of IV therapy. Safety and off-treatment responses will be presented for those patients who have received 4 or more courses of IV alefacept. These data will provide important information regarding longer-term use of alefacept and further define the safety profile of this selective anti-T-cell agent.
Dr Feldman has received support from Galderma Laboratories, L.P. The Center for Dermatology Research is funded by an unrestricted grant from Galderma Laboratories, L.P.
Disclosure not available at press time. Supported in part by Biogen, Inc.
P587 ALEFACEPT IN COMBINATION WITH TAPERING DOSES OF METHOTREXATE IN PATIENTS WITH PSORIASIS Alan Menter, MD, Texas Dermatology Associates, Dallas, TX, United States, William Abramovits, Texas Dermatology Associates, Dallas, TX, United States, Jennifer Cather, Texas Dermatology Associates, Dallas, TX, United States Methotrexate is an effective systemic treatment for moderate to severe psoriasis, but its use is limited because of safety concerns. For example, short-term exposure is associated with bone marrow toxicity and long-term therapy with hepatotoxicity. Patients receiving methotrexate require routine blood and platelet counts, liver function tests, and blood urea nitrogen and creatinine levels. A liver biopsy is required at cumulative methotrexate doses of 1.0-1.5 g and every 1-1.5 g thereafter provided liver function tests and biopsy findings are normal. Methotrexate also has numerous drug interactions, which may result in additive or synergistic toxicity. The generalized immunosuppressive effects of methotrexate may increase the potential for infections and malignancies. In addition, it is an abortifacient and a teratogen. Alefacept is the first biologic agent to be approved in the US for the treatment of moderate to severe chronic plaque psoriasis. This agent has a remittive mechanism of action—it selectively reduces the T-cell population implicated in the pathogenesis of psoriasis. Alefacept has demonstrated placebo-like tolerability in clinical studies, with no evidence of an increased risk for infections or malignancies. In clinical practice, patients being treated with methotrexate need a safe and effective strategy for discontinuing methotrexate and initiating alefacept. An open-label study is underway to determine the consistency and durability of response achieved by tapering the dose of methotrexate while initiating alefacept therapy in adult patients with chronic plaque psoriasis. All participants must be receiving methotrexate, have achieved at least 50% improvement in psoriasis while on methotrexate, and be naı¨ve to alefacept therapy. At the initiation of the study, the patient’s weekly dose of methotrexate will be reduced by 2.5 mg per week. At subsequent visits, each patient will be instructed about the dose of methotrexate to be used until the following visit. Depending on the patient’s dose of methotrexate entering the study, the weekly dose will be tapered over approximately 8 weeks with the aim of discontinuing methotrexate. Alefacept will be administered as 15 mg IM or 7.5 mg IV once weekly for 12 weeks followed by 4 months of observation. Assessments will include skin and disease evaluations, adverse events, and laboratory tests as specified in the package inserts for alefacept and methotrexate. Disclosure not available at press time. Sponsored in part by Biogen, Inc.
MARCH 2004
P589 ALEFACEPT IN THE TREATMENT OF PSORIATIC NAIL DISEASE Bruce E Strober, MD, PhD, New York University School of Medicine, New York, NY, United States, Chris Cassetty, MD, New York University School of Medicine, New York, NY, United States Alefacept effectively treats moderate to severe plaque psoriasis by selectively reducing memory T cells. We examined the ability of alefacept to treat dystrophic nails of subjects with moderate to severe psoriasis. Subjects received alefacept 15 mg intramuscularly for 12 consecutive weeks. Photographs were taken of a target dystrophic nail at baseline and approximately every 4 weeks during and after the course of alefacept. Both the total CD4⫹ T-cell count and the Psoriasis Area and Severity Index (PASI) score were also measured at each evaluation. We demonstrate that patients who showed improvement in the target nail also displayed a reduction in their CD4⫹ T-cell count over the course of therapy and a concomitant reduction in their PASI score. Patients who showed no improvement in the target nail showed no T-cell count reduction and no improvement in their PASI score. Therefore, improvement in nail dystrophy during alefacept therapy may be expected to mirror both clinical improvement in the cutaneous exam and the reduction in the CD4⫹ T-cell count. Disclosure not available at press time. Sponsored in part by Biogen, Inc.
J AM ACAD DERMATOL
P151
P588
CLASS I TOPICAL CORTICOSTEROID USE FOR PSORIASIS PATIENTS IN AN ACADEMIC PRACTICE Dan Pearce, MD, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, United States, Alan Fleischer, Jr., MD, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, United States, Steven Feldman, MD, PhD, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, United States Background: Psoriasis is a chronic skin disorder that can have profound QOL implications for patients. For the clinician, the treatment of psoriasis is complicated by the availability of numerous topical agents, systemic agents, as well as phototherapy. Of the topical preparations available, the ultra-high potency corticosteroids, or Class I steroids, have an important role in treating psoriasis in a wide spectrum of disease. Purpose: The purpose of this study was to examine the prescribing patterns of ultra-high potency, or Class I, topical steroids in patients with various types of psoriasis. Methods: A retrospective chart review of greater that 500 patients with psoriasis from an academic dermatology practice was performed. Class I steroid use was defined as those patients that were observed to be currently using Clobetasol, Halobetasol, Augmented Betamethasone Results: 79% of patients in our sample were prescribed topical steroids of any class while 46% of patients were prescribed a Class I steroid. Thus, greater than 58% of patients receiving topical steroid therapy received a Class I agent. 11% of patient’s prescribed class I steroids were also receiving systemic therapy for their psoriasis. Conversely, 35% of patients who were receiving systemic therapy were also receiving Class I topicals. Discussion: The use of Class I topical steroids is fairly commonplace, even among patients on systemic therapy for severe psoriasis. These ultra-high potency topicals provide a relatively safe adjunct to systemic therapy and remain a mainstay of psoriasis therapy.
LONG-TERM USE OF INTRAVENOUS ALEFACEPT: SAFETY AND OFF-TREATMENT RESPONSES IN PATIENTS WHO HAVE RECEIVED FOUR OR MORE COURSES OF THERAPY Alan Menter, MD, Texas Dermatology Associates, Dallas, TX, United States, Jennifer Cather, Texas Dermatology Associates, Dallas, TX, United States Psoriasis is a chronic disease that often requires repeated courses of treatment to maintain satisfactory control of disease signs and symptoms. Alefacept is a fully human LFA-3/IgG1 fusion protein that inhibits T-cell activation and stimulates apoptosis of memory (CD45RO⫹) T cells, which have been implicated in psoriasis pathogenesis. Alefacept is the first biologic agent approved for the treatment of adult patients with chronic plaque psoriasis. The safety and efficacy of alefacept, administered as a once weekly injection (either intravenous [IV] bolus or intramuscular) for 12 weeks followed by a 12-week observation period, are well documented for 1 and 2 courses of therapy. As part of the clinical development program, patients who completed phase 2 studies were eligible to participate in an open-label extension study to determine the safety and efficacy of repeated courses of alefacept. The drug was administered at a fixed dose of 7.5 mg by 30-second IV bolus once weekly for 12 weeks followed by a 12-week observation period. Subjects may receive repeated courses of alefacept if their psoriasis recurs 12 weeks or more after therapy is completed and their CD4⫹ T-cell count is at or above the lower limit of normal. Efficacy is assessed by the percentage of responders (as measured by PASI score and physician global assessment), the duration of response from course to course, the time to retreatment, and the reasons for attrition from the study. Adverse events, including infection and malignancy rates, and clinical laboratory data are collected weekly during therapy and for 12 weeks after each course. This is an ongoing trial. Data through 3 courses of therapy have been previously presented and published (Lowe NJ, et al. Int J Dermatol 2003;42:224-230). Some patients have now received up to 8 courses of IV therapy. Safety and off-treatment responses will be presented for those patients who have received 4 or more courses of IV alefacept. These data will provide important information regarding longer-term use of alefacept and further define the safety profile of this selective anti-T-cell agent.
Dr Feldman has received support from Galderma Laboratories, L.P. The Center for Dermatology Research is funded by an unrestricted grant from Galderma Laboratories, L.P.
Disclosure not available at press time. Supported in part by Biogen, Inc.
P587 ALEFACEPT IN COMBINATION WITH TAPERING DOSES OF METHOTREXATE IN PATIENTS WITH PSORIASIS Alan Menter, MD, Texas Dermatology Associates, Dallas, TX, United States, William Abramovits, Texas Dermatology Associates, Dallas, TX, United States, Jennifer Cather, Texas Dermatology Associates, Dallas, TX, United States Methotrexate is an effective systemic treatment for moderate to severe psoriasis, but its use is limited because of safety concerns. For example, short-term exposure is associated with bone marrow toxicity and long-term therapy with hepatotoxicity. Patients receiving methotrexate require routine blood and platelet counts, liver function tests, and blood urea nitrogen and creatinine levels. A liver biopsy is required at cumulative methotrexate doses of 1.0-1.5 g and every 1-1.5 g thereafter provided liver function tests and biopsy findings are normal. Methotrexate also has numerous drug interactions, which may result in additive or synergistic toxicity. The generalized immunosuppressive effects of methotrexate may increase the potential for infections and malignancies. In addition, it is an abortifacient and a teratogen. Alefacept is the first biologic agent to be approved in the US for the treatment of moderate to severe chronic plaque psoriasis. This agent has a remittive mechanism of action—it selectively reduces the T-cell population implicated in the pathogenesis of psoriasis. Alefacept has demonstrated placebo-like tolerability in clinical studies, with no evidence of an increased risk for infections or malignancies. In clinical practice, patients being treated with methotrexate need a safe and effective strategy for discontinuing methotrexate and initiating alefacept. An open-label study is underway to determine the consistency and durability of response achieved by tapering the dose of methotrexate while initiating alefacept therapy in adult patients with chronic plaque psoriasis. All participants must be receiving methotrexate, have achieved at least 50% improvement in psoriasis while on methotrexate, and be naı¨ve to alefacept therapy. At the initiation of the study, the patient’s weekly dose of methotrexate will be reduced by 2.5 mg per week. At subsequent visits, each patient will be instructed about the dose of methotrexate to be used until the following visit. Depending on the patient’s dose of methotrexate entering the study, the weekly dose will be tapered over approximately 8 weeks with the aim of discontinuing methotrexate. Alefacept will be administered as 15 mg IM or 7.5 mg IV once weekly for 12 weeks followed by 4 months of observation. Assessments will include skin and disease evaluations, adverse events, and laboratory tests as specified in the package inserts for alefacept and methotrexate. Disclosure not available at press time. Sponsored in part by Biogen, Inc.
MARCH 2004
P589 ALEFACEPT IN THE TREATMENT OF PSORIATIC NAIL DISEASE Bruce E Strober, MD, PhD, New York University School of Medicine, New York, NY, United States, Chris Cassetty, MD, New York University School of Medicine, New York, NY, United States Alefacept effectively treats moderate to severe plaque psoriasis by selectively reducing memory T cells. We examined the ability of alefacept to treat dystrophic nails of subjects with moderate to severe psoriasis. Subjects received alefacept 15 mg intramuscularly for 12 consecutive weeks. Photographs were taken of a target dystrophic nail at baseline and approximately every 4 weeks during and after the course of alefacept. Both the total CD4⫹ T-cell count and the Psoriasis Area and Severity Index (PASI) score were also measured at each evaluation. We demonstrate that patients who showed improvement in the target nail also displayed a reduction in their CD4⫹ T-cell count over the course of therapy and a concomitant reduction in their PASI score. Patients who showed no improvement in the target nail showed no T-cell count reduction and no improvement in their PASI score. Therefore, improvement in nail dystrophy during alefacept therapy may be expected to mirror both clinical improvement in the cutaneous exam and the reduction in the CD4⫹ T-cell count. Disclosure not available at press time. Sponsored in part by Biogen, Inc.
J AM ACAD DERMATOL
P151