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Improvement of severe psoriatic nail involvement with alefacept therapy
P562
P564
IMPROVEMENT IN NAIL PSORIASIS WITH ALEFACEPT Jenny Sobera, MD, University of Alabama-Birmingham, Birmingham, AL, United States, Charles Parrish, MD, University of Alabama-Birmingham, Birmingham, AL, United States, Boni Elewski, MD, University of Alabama-Birmingham, Birmingham, AL, United States Chronic plaque psoriasis is a disease that affects more than 2% of the world’s population. Nail psoriasis, which is prevalent in approximately 50% of psoriasis patients, causes significant negative impact on quality of life. Nail changes include pitting, localized areas of discoloration, nail thickening, onycholysis, and subungual hyperkeratosis and may lead to disfiguring changes. Treatment options are limited. 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 has demonstrated excellent safety and efficacy in multiple randomized, placebo-controlled studies and retreatment trials. To understand how to optimize the use of alefacept for the treatment of nail psoriasis, an open-label study was conducted to determine the safety and efficacy under conditions reflective of the clinical practice setting. Efficacy was assessed by the percentage of responders (as measured by NAPSI score and physician global assessment). NAPSI was used to determine a target nail score as well as the global assessment score of all nails. Only patients 319 years of age, with CD4⫹ T-cell counts at or above the lower limit of normal, with a diagnosis of moderately severe nail psoriasis, and a PASI ⬎ 10 have been included to receive a 12-week course of alefacept 7.5 mg weekly. Each course consists of 12 once-weekly intravascular injections followed by 12 weeks of observation. Alefacept may be an appropriate alternative for nail psoriasis patients for whom conventional treatments are either ineffective or inappropriate, based upon lack of response to available agents, or contraindication or intolerance to the existing therapy as determined by the practicing physician.
IMPROVEMENT OF SEVERE PSORIATIC NAIL INVOLVEMENT WITH ALEFACEPT THERAPY Jeffrey P Callen, MD, University of Louisville, Louisville, KY, United States Background: Alefacept has been recently approved for the treatment of chronic plaque psoriasis vulgaris. Its use for the treatment of nail disease has not been documented. Alefacept is believed to be active in psoriasis by affecting the interaction between LFA-3 on an antigen presenting cell and CD2 on activated T-cells. In addition, alefacept binds to activated CD4⫹CD45RO⫹ cells and through interaction with NK cells causes T-cell apoptosis. Affects on nail disease have not been presented in the formal studies of this drug. This poster presents my observation of a single patient with severe psoriatic nail involvement whose nails improved in conjunction with improvement of his overall disease. Observation: A 41-year-old man with a history of psoriasis vulgaris and mild psoriatic arthritis was treated with intramuscular alefacept in early 2003. His only other medical condition was a seizure disorder. His previous therapies included etretinate, methotrexate, PUVA therapy, inpatient UVB/tar therapy, cyclosporin and etanercept. He responded nicely to cyclosporin, but had nausea that limited his ability to continue the drug long-term. Etanercept was very effective in controlling his disease, but on January 1, 2003 because of changes in his insurance coverage he was not able to afford to continue this drug. During the subsequent 3-months he elected to stop all therapy while waiting to begin therapy with alefacept. Prior to initiation of alefacept his psoriasis flared, involving roughly 75% of his body surface and his nails became completely dystrophic and marked subungual debris was noted. For roughly 4 weeks after initiating therapy there was little change in his disease activity or extent, however in parallel with a fall in his CD4 cell count his nails improved. Conclusion: Alefacept appeared to be effective in this patient for both his nails and his severe plaque-type disease. Alefacept may be useful for patients with psoriatic nail disease.
Jenny Sobera-None Charles Parrish-None Boni Elewski-No conflicts relevant to this study. This study was supported by a grant from Biogen, Inc.
Consultant: Biogen, Amgen, Centocor Honorarium directly or indirectly: Genentech, Biogen, Roche, Amgen, Centocor Stockholder-Johnson & Johnson, Amgen A grant from Biogen will support the production of this poster.
P565
P563 SAFETY OF CYCLOSPORINE IN PATIENTS WITH PSORIASIS Jose´ Marı´a Hernanz, Hospital Gregorio Maran˜ o´ n, Madrid, Spain, Francisco Vanaclocha, Hospital 12 de OCtubre, Madrid, Spain, Lluis Puig, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, Esteba´n Daude´n, Hospital de la Princesa, Madrid, Spain Introduction: Cyclosporine has proven to be a safe treatment in patients with psoriasis. Material and Methods: 294 patients with psoriasis treated with cyclosporine were included in the study by 55 Spanish dermatologists. The demographic and clinical data were collected as well as the PDI (Psoriasis Disability Index) and EQ-5D (EuroQol-5D) questionnaires during the inclusion visit and again after 3, 6, and 12 months. Results: During the follow-up period of the study only 24.1% of patients showed clinical and analytic alterations. Of these, 7.8% exhibited higher blood pressure and 5.4% experimented an increase in plasmatic creatinine. The most usual symptoms were hypertrichosis (9.1%), asthenia, cephalalgia, cramps, muscular pain, and vomits/diarrhea. Adverse effects were typified according to the sort of alterations observed. The most frequent adverse reactions were skin alterations (22.7%), kidney toxicity (9.1%), and gastric alterations (9.1%). Only two of these adverse events were considered severe. Incidence of adverse events: Higher blood pressure 2.38 Cephalalgia 1.36 Hypertrichosis 2.04 Hypertriglyceridemy 1.36 Increase creatinine 1.7 Vomits/diarrhea 1.36 Asthenia 1.36 Erythema/Flushing 0.68 Cramps/muscular pain 1.36 Furunculosis 0.68 Conclusions: One year treatment with cyclosporine at mean dose of 3.5mg/Kg/day has shown good clinical tolerability.
MARCH 2004
SUSTAINED IMPROVEMENT IN ACTIVITIES OF DAILY LIVING AND VITALITY IN PATIENTS WITH PSORIATIC ARTHRITIS TREATED WITH ETANERCEPT Lee A. Wanke, MS, Amgen, Thousand Oaks, CA, United States, Philip Mease, MD, Minor and James Medical Center, Seattle, WA, United States, Alice Gottlieb, MD, UMDNJ Robert Wood Johnson Medical School, New Brunswick, NJ, United States, Daniel Burge, MD, Amgen, Thousand Oaks, CA, United States Background and Purpose: Etanercept significantly improved clinical signs and symptoms as well as health-related quality of life in a six-month phase 3 trial of patients with psoriatic arthritis. The purpose of this study was to determine the impact of etanercept on individual activities of daily living (ADL) as well as vitality and to determine the sustainability of that response. Methods: Patients with active psoriatic arthritis who did not respond to conventional therapy were randomized to either etanercept 25mg subcutaneously twice weekly (n ⫽ 101) or matching placebo (n ⫽ 104). Patients completed the Health Assessment Questionnaire (HAQ), which also included validated measures of vitality (from the SF-36). The HAQ consists of eight categories, which comprise 24 questions related to ADL. At the end of the blinded phase of the study (24 weeks), patients continued to receive etanercept in an open-label phase, and continued to complete this instrument. Data are currently available for up to 72 weeks in 69 patients. Results: Results are presented in the table. During the blinded phase of the trial, the functional disability index (HAQ score) improved from 1.1 at baseline to 0.5 at 24 weeks (scale 0-3, with a lower number signifying less disability; 0.43 units ⫽ clinically meaningful change). The improvement in functional disability (a change score of 0.6) was mirrored by the improvement in each of the ADL subscales (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities), where the range was change scores of 0.5-0.6. This improvement was sustained in both the index score and the individual scores through 72 weeks (range 0.5-0.8 units). Patients’ vitality also improved, by a mean of 13.6 units during the blinded phase and 15.3 units at 72 weeks (scale 0-100, with a higher number signifying more vitality; 8 units ⫽ clinically meaningful change). Etanercept significantly improved functional ability, all activities of daily living, and vitality in this group of patients. Statistically significant changes occurred early and were sustained. Conclusion: Patients with psoriatic arthritis treated with etanercept are better able to perform activities of daily living and also experience increased vitality. These changes are clinically meaningful, occur early in therapy, and are sustained. Lee Wanke and Daniel Burge are full-time employees of Amgen. Philip Mease and Alice Gottlieb have provided consultative work and have participated in clinical trials sponsored by Amgen. This study was supported by Amgen.
J AM ACAD DERMATOL
P145
P564
IMPROVEMENT IN NAIL PSORIASIS WITH ALEFACEPT Jenny Sobera, MD, University of Alabama-Birmingham, Birmingham, AL, United States, Charles Parrish, MD, University of Alabama-Birmingham, Birmingham, AL, United States, Boni Elewski, MD, University of Alabama-Birmingham, Birmingham, AL, United States Chronic plaque psoriasis is a disease that affects more than 2% of the world’s population. Nail psoriasis, which is prevalent in approximately 50% of psoriasis patients, causes significant negative impact on quality of life. Nail changes include pitting, localized areas of discoloration, nail thickening, onycholysis, and subungual hyperkeratosis and may lead to disfiguring changes. Treatment options are limited. 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 has demonstrated excellent safety and efficacy in multiple randomized, placebo-controlled studies and retreatment trials. To understand how to optimize the use of alefacept for the treatment of nail psoriasis, an open-label study was conducted to determine the safety and efficacy under conditions reflective of the clinical practice setting. Efficacy was assessed by the percentage of responders (as measured by NAPSI score and physician global assessment). NAPSI was used to determine a target nail score as well as the global assessment score of all nails. Only patients 319 years of age, with CD4⫹ T-cell counts at or above the lower limit of normal, with a diagnosis of moderately severe nail psoriasis, and a PASI ⬎ 10 have been included to receive a 12-week course of alefacept 7.5 mg weekly. Each course consists of 12 once-weekly intravascular injections followed by 12 weeks of observation. Alefacept may be an appropriate alternative for nail psoriasis patients for whom conventional treatments are either ineffective or inappropriate, based upon lack of response to available agents, or contraindication or intolerance to the existing therapy as determined by the practicing physician.
IMPROVEMENT OF SEVERE PSORIATIC NAIL INVOLVEMENT WITH ALEFACEPT THERAPY Jeffrey P Callen, MD, University of Louisville, Louisville, KY, United States Background: Alefacept has been recently approved for the treatment of chronic plaque psoriasis vulgaris. Its use for the treatment of nail disease has not been documented. Alefacept is believed to be active in psoriasis by affecting the interaction between LFA-3 on an antigen presenting cell and CD2 on activated T-cells. In addition, alefacept binds to activated CD4⫹CD45RO⫹ cells and through interaction with NK cells causes T-cell apoptosis. Affects on nail disease have not been presented in the formal studies of this drug. This poster presents my observation of a single patient with severe psoriatic nail involvement whose nails improved in conjunction with improvement of his overall disease. Observation: A 41-year-old man with a history of psoriasis vulgaris and mild psoriatic arthritis was treated with intramuscular alefacept in early 2003. His only other medical condition was a seizure disorder. His previous therapies included etretinate, methotrexate, PUVA therapy, inpatient UVB/tar therapy, cyclosporin and etanercept. He responded nicely to cyclosporin, but had nausea that limited his ability to continue the drug long-term. Etanercept was very effective in controlling his disease, but on January 1, 2003 because of changes in his insurance coverage he was not able to afford to continue this drug. During the subsequent 3-months he elected to stop all therapy while waiting to begin therapy with alefacept. Prior to initiation of alefacept his psoriasis flared, involving roughly 75% of his body surface and his nails became completely dystrophic and marked subungual debris was noted. For roughly 4 weeks after initiating therapy there was little change in his disease activity or extent, however in parallel with a fall in his CD4 cell count his nails improved. Conclusion: Alefacept appeared to be effective in this patient for both his nails and his severe plaque-type disease. Alefacept may be useful for patients with psoriatic nail disease.
Jenny Sobera-None Charles Parrish-None Boni Elewski-No conflicts relevant to this study. This study was supported by a grant from Biogen, Inc.
Consultant: Biogen, Amgen, Centocor Honorarium directly or indirectly: Genentech, Biogen, Roche, Amgen, Centocor Stockholder-Johnson & Johnson, Amgen A grant from Biogen will support the production of this poster.
P565
P563 SAFETY OF CYCLOSPORINE IN PATIENTS WITH PSORIASIS Jose´ Marı´a Hernanz, Hospital Gregorio Maran˜ o´ n, Madrid, Spain, Francisco Vanaclocha, Hospital 12 de OCtubre, Madrid, Spain, Lluis Puig, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, Esteba´n Daude´n, Hospital de la Princesa, Madrid, Spain Introduction: Cyclosporine has proven to be a safe treatment in patients with psoriasis. Material and Methods: 294 patients with psoriasis treated with cyclosporine were included in the study by 55 Spanish dermatologists. The demographic and clinical data were collected as well as the PDI (Psoriasis Disability Index) and EQ-5D (EuroQol-5D) questionnaires during the inclusion visit and again after 3, 6, and 12 months. Results: During the follow-up period of the study only 24.1% of patients showed clinical and analytic alterations. Of these, 7.8% exhibited higher blood pressure and 5.4% experimented an increase in plasmatic creatinine. The most usual symptoms were hypertrichosis (9.1%), asthenia, cephalalgia, cramps, muscular pain, and vomits/diarrhea. Adverse effects were typified according to the sort of alterations observed. The most frequent adverse reactions were skin alterations (22.7%), kidney toxicity (9.1%), and gastric alterations (9.1%). Only two of these adverse events were considered severe. Incidence of adverse events: Higher blood pressure 2.38 Cephalalgia 1.36 Hypertrichosis 2.04 Hypertriglyceridemy 1.36 Increase creatinine 1.7 Vomits/diarrhea 1.36 Asthenia 1.36 Erythema/Flushing 0.68 Cramps/muscular pain 1.36 Furunculosis 0.68 Conclusions: One year treatment with cyclosporine at mean dose of 3.5mg/Kg/day has shown good clinical tolerability.
MARCH 2004
SUSTAINED IMPROVEMENT IN ACTIVITIES OF DAILY LIVING AND VITALITY IN PATIENTS WITH PSORIATIC ARTHRITIS TREATED WITH ETANERCEPT Lee A. Wanke, MS, Amgen, Thousand Oaks, CA, United States, Philip Mease, MD, Minor and James Medical Center, Seattle, WA, United States, Alice Gottlieb, MD, UMDNJ Robert Wood Johnson Medical School, New Brunswick, NJ, United States, Daniel Burge, MD, Amgen, Thousand Oaks, CA, United States Background and Purpose: Etanercept significantly improved clinical signs and symptoms as well as health-related quality of life in a six-month phase 3 trial of patients with psoriatic arthritis. The purpose of this study was to determine the impact of etanercept on individual activities of daily living (ADL) as well as vitality and to determine the sustainability of that response. Methods: Patients with active psoriatic arthritis who did not respond to conventional therapy were randomized to either etanercept 25mg subcutaneously twice weekly (n ⫽ 101) or matching placebo (n ⫽ 104). Patients completed the Health Assessment Questionnaire (HAQ), which also included validated measures of vitality (from the SF-36). The HAQ consists of eight categories, which comprise 24 questions related to ADL. At the end of the blinded phase of the study (24 weeks), patients continued to receive etanercept in an open-label phase, and continued to complete this instrument. Data are currently available for up to 72 weeks in 69 patients. Results: Results are presented in the table. During the blinded phase of the trial, the functional disability index (HAQ score) improved from 1.1 at baseline to 0.5 at 24 weeks (scale 0-3, with a lower number signifying less disability; 0.43 units ⫽ clinically meaningful change). The improvement in functional disability (a change score of 0.6) was mirrored by the improvement in each of the ADL subscales (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities), where the range was change scores of 0.5-0.6. This improvement was sustained in both the index score and the individual scores through 72 weeks (range 0.5-0.8 units). Patients’ vitality also improved, by a mean of 13.6 units during the blinded phase and 15.3 units at 72 weeks (scale 0-100, with a higher number signifying more vitality; 8 units ⫽ clinically meaningful change). Etanercept significantly improved functional ability, all activities of daily living, and vitality in this group of patients. Statistically significant changes occurred early and were sustained. Conclusion: Patients with psoriatic arthritis treated with etanercept are better able to perform activities of daily living and also experience increased vitality. These changes are clinically meaningful, occur early in therapy, and are sustained. Lee Wanke and Daniel Burge are full-time employees of Amgen. Philip Mease and Alice Gottlieb have provided consultative work and have participated in clinical trials sponsored by Amgen. This study was supported by Amgen.
J AM ACAD DERMATOL
P145