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Use of extended courses of alefacept in the treatment of moderate-to-severe psoriasis
P2771
P2773
Evaluation of the efficacy and safety of alefacept in patients for whom conventional psoriasis therapies are ineffective or inappropriate Joel Sclessinger, MD, Skin Specialists PC, Omaha, NE, United States; Robert Pariser, MD, Virginia Clinical Research, Norfolk, VA, United States; Sharon Park, PharmD, Astellas Pharma U.S., Inc, Deerfield, IL, United States; Gina Wierz, Astellas Pharma U.S., Inc, Deerfield, IL, United States Objective: To assess the efficacy and safety of alefacept in patients for whom conventional therapy was ineffective or inappropriate.
Home UVB plus low dose acitretin as a psoriasis treatment Christopher Yelverton, MD, MBA, Wake Forest University Health Sciences, Winston-Salem, NC, United States; Daniel Pearce, MD, Wake Forest University Health Sciences, Winston-Salem, NC, United States; Steven Feldman, MD, PhD, Wake Forest University Health Sciences, Winston-Salem, NC, United States
Methods: Patients with chronic plaque psoriasis requiring systemic therapy were eligible for enrollment if 3 or more conventional therapies were ineffective (after treatment) or inappropriate (for initiating treatment). Patients were randomized 2:1 to receive either intramuscular (IM) alefacept 15 mg or placebo once weekly for 12 weeks followed by at least 12-weeks of observation (Course A). All patients who completed Course A were eligible for an open-label retreatment course of alefacept (Course B) if their psoriasis progressed to ‘‘moderate’’ or worse. The primary endpoint was the proportion of patients who achieved PASI-50 or better at 2 weeks after the last dose of Course A. Results: A total of 195 patients were enrolled (alefacept, n = 130; placebo, n = 65); 3 or more conventional psoriasis therapies were ineffective or inappropriate in 98% of patients. Approximately 80% of patients in this study had previously received 3 or more ineffective conventional treatments for psoriasis. At 2 weeks after the dosing period in Course A, 24% of patients treated with alefacept achieved PASI-50, compared with 11% of patients treated with placebo (p = 0.030). Of patients treated with 2 courses of alefacept, 43% achieved PASI-50 at 2 weeks after the dosing period in Course B. The benefit of treatment with alefacept was also demonstrated through additional PASI and Physician’s Global Assessment endpoints. The incidence of adverse events, including infections and serious adverse events, reported in Course A, was similar between treatment groups. The overall incidence of adverse events was lower in Course B compared with Course A. CD41 T-cell counts were similar to that reported in previous studies for alefacept, and the pharmacodynamic profile of alefacept was not changed with an additional course of treatment. No clinically significant difference were observed in CD41 T-cell counts as a result of lymphocyte monitoring every 2 weeks (Course A) compared with every 4 weeks (Course B).
Psoriasis is a common, chronic, immune-mediated disease with profound health and quality of life impact. The treatment of psoriasis is complex at times due to the disease’s characteristics and the cumbersome treatments. Combination regimens are the standard of care and are particularly useful in moderate-to-severe patients as they provide enhanced efficacy and minimize the potential for adverse events. Acitretin and narrow band ultraviolet light are 2 therapies that are approved for psoriasis; when used together this regimen has efficacy similar to some of the best available treatments. Home ultraviolet (UV) light provides greater accessibility for some patients compared to office-based phototherapy. We plan to present adherence, efficacy and short-term safety data from an open trial using home phototherapy in combination with acitretin for plaque type psoriasis. We expect that the combination of acitretin and home based phototherapy will provide a convenient, cost-effective method of treating psoriasis. This study was supported by grants from Connetics Corporation and National Biologic Corporation.
Conclusion: Alefacept may be an effective and well-tolerated treatment option in patients for whom 3 or more conventional psoriasis treatments are ineffective or inappropriate. This study was originally sponsored by Biogen Idec. Astellas Pharma U.S., Inc. acquired ownership of Amevive effective April 14, 2006 and has subsequently supported the presentation of this study by providing material resources and editorial support.
P2774 Use of extended courses of alefacept in the treatment of moderate-tosevere psoriasis Aditya Gupta, MD, PhD, Mediprobe Research Inc, London, ON, Canada
Vitiligo is a progressive disorder characterized by depigmentation of the epidermis that affects 1% to 2% of the world’s population. Although concomitant presentation of vitiligo with psoriasis is uncommon, several cases have been reported previously in the literature. The etiology of vitiligo is not clear, but it appears to be an autoimmune disease with T-cell involvement. Efalizumab is a T-celletargeted recombinant humanized monoclonal antibody approved for the treatment of adults with chronic moderate to severe plaque psoriasis. Here we describe the case of a patient who presented with vitiligo and psoriasis and was treated with efalizumab to reduce his symptoms of psoriasis. The patient is a 43-year-old Hispanic male whose history includes more than 10 years of vitiligo and more than 5 years of psoriasis. He had been managing his psoriasis with topical steroids. Over the course of his vitiligo and psoriatic disease, he had been treated with numerous therapies, including calcipotriene and topical halobetasol, topical anthralin, topical tazarotene, oral antibiotics, topical steroids of varying strengths, and phototherapy. He switched to treatment with topical tacrolimus followed by oral acitretin when his vitiligo became more prominent in the Spring. He developed pruritus that did not respond to topical corticosteroid treatment. Since progression of vitiligo brought on greater discomfort due to the burning effect of phototherapy, it was appropriate and prudent to shift away from this modality and into the use of a biologic agent such as efalizumab. He initiated efalizumab with a 0.7 mg/kg conditioning dose, and continued thereafter with 1 mg/kg/wk. After 2 months of efalizumab therapy, the pruritus had resolved, scales had disappeared, and plaque elevation had reduced. The patient has remained on efalizumab therapy with no evidence of exacerbation of vitiligo. This case is illustrative of a patient with vitiligo who was treated with efalizumab without adding further complications to his treatment regimen.
Alefacept is an immunosuppressive dimeric fusion protein that interferes with T-lymphocyte activation. This action has been shown in Phase II and III clinical trials to effectively target psoriasis lesions as demonstrated by reduction in the psoriasis area and severity index (PASI) scores during the standard 12-week dosing phase followed by a 12-week follow-up phase. A 75% reduction in PASI score (PASI-75) was found in 28% of subjects during a preliminary 12-week dosing/12-week follow-up. Extension of treatment by providing a second 12-week dosing/12-week follow-up period was studied and showed that PASI-75 was achieved in 40% of subjects, demonstrating that longer dosing periods could improve the efficacy of treatment without compromising patient safety. Similarly, an extended 16-week course of alefacept also showed efficacy and safety, and suggested that extended dosing could be performed without the 12-week follow-up period between dosing phases. Based on this data, an open-label extended dosing study was performed to investigate the efficacy and safety of continuous dosing with alefacept for up to 24 weeks. Subjects with moderate to severe psoriasis were enrolled and provided with a standard 12-week dosing of alefacept. If the subject had not shown a 90% decrease in PASI score (PASI-90) at week 12, dosing was continued until week 16. Similarly, at weeks 16 and 20, subjects continued with weekly dosing if they did not show PASI-90 or greater. All dosing was stopped at week 24, and subjects continued to be followedup to week 28 and week 36. Approximately 25 patients have been enrolled into the trial currently. Initial data shows that for subjects who are beyond week 12, 42% have achieved PASI-75 by week 24, suggesting that continuous dosing provides similar efficacy to extended-pause dosing with similar safety profile. Most subjects continued to require dosing beyond week 16 and 20. One subject achieved PASI-90 at week 16 and discontinued drug use. PASI-90 was maintained to week 36 without further drug use. The mean reduction in PASI score from baseline increased with treatment duration from 18% at week 12, to 40% at week 16, and 54% at week 24. Up to 30 subjects will be followed to week 36 at the end of the trial. This interim data suggests that continuous dosing with alefacept is safe and effective, and a 12-week follow-up phase may not be required before initiating repeat dosing.
Development and production supported by Genentech, Inc.
Partial sponsor: Astellas Canada.
P2772 Efalizumab treatment of a patient presenting with vitiligo and psoriasis Adolfo Fernandez-Obregon, MD, Hudson Dermatology and Skin Cancer Center, Hoboken, NJ, United States
AB192
J AM ACAD DERMATOL
FEBRUARY 2007
P2773
Evaluation of the efficacy and safety of alefacept in patients for whom conventional psoriasis therapies are ineffective or inappropriate Joel Sclessinger, MD, Skin Specialists PC, Omaha, NE, United States; Robert Pariser, MD, Virginia Clinical Research, Norfolk, VA, United States; Sharon Park, PharmD, Astellas Pharma U.S., Inc, Deerfield, IL, United States; Gina Wierz, Astellas Pharma U.S., Inc, Deerfield, IL, United States Objective: To assess the efficacy and safety of alefacept in patients for whom conventional therapy was ineffective or inappropriate.
Home UVB plus low dose acitretin as a psoriasis treatment Christopher Yelverton, MD, MBA, Wake Forest University Health Sciences, Winston-Salem, NC, United States; Daniel Pearce, MD, Wake Forest University Health Sciences, Winston-Salem, NC, United States; Steven Feldman, MD, PhD, Wake Forest University Health Sciences, Winston-Salem, NC, United States
Methods: Patients with chronic plaque psoriasis requiring systemic therapy were eligible for enrollment if 3 or more conventional therapies were ineffective (after treatment) or inappropriate (for initiating treatment). Patients were randomized 2:1 to receive either intramuscular (IM) alefacept 15 mg or placebo once weekly for 12 weeks followed by at least 12-weeks of observation (Course A). All patients who completed Course A were eligible for an open-label retreatment course of alefacept (Course B) if their psoriasis progressed to ‘‘moderate’’ or worse. The primary endpoint was the proportion of patients who achieved PASI-50 or better at 2 weeks after the last dose of Course A. Results: A total of 195 patients were enrolled (alefacept, n = 130; placebo, n = 65); 3 or more conventional psoriasis therapies were ineffective or inappropriate in 98% of patients. Approximately 80% of patients in this study had previously received 3 or more ineffective conventional treatments for psoriasis. At 2 weeks after the dosing period in Course A, 24% of patients treated with alefacept achieved PASI-50, compared with 11% of patients treated with placebo (p = 0.030). Of patients treated with 2 courses of alefacept, 43% achieved PASI-50 at 2 weeks after the dosing period in Course B. The benefit of treatment with alefacept was also demonstrated through additional PASI and Physician’s Global Assessment endpoints. The incidence of adverse events, including infections and serious adverse events, reported in Course A, was similar between treatment groups. The overall incidence of adverse events was lower in Course B compared with Course A. CD41 T-cell counts were similar to that reported in previous studies for alefacept, and the pharmacodynamic profile of alefacept was not changed with an additional course of treatment. No clinically significant difference were observed in CD41 T-cell counts as a result of lymphocyte monitoring every 2 weeks (Course A) compared with every 4 weeks (Course B).
Psoriasis is a common, chronic, immune-mediated disease with profound health and quality of life impact. The treatment of psoriasis is complex at times due to the disease’s characteristics and the cumbersome treatments. Combination regimens are the standard of care and are particularly useful in moderate-to-severe patients as they provide enhanced efficacy and minimize the potential for adverse events. Acitretin and narrow band ultraviolet light are 2 therapies that are approved for psoriasis; when used together this regimen has efficacy similar to some of the best available treatments. Home ultraviolet (UV) light provides greater accessibility for some patients compared to office-based phototherapy. We plan to present adherence, efficacy and short-term safety data from an open trial using home phototherapy in combination with acitretin for plaque type psoriasis. We expect that the combination of acitretin and home based phototherapy will provide a convenient, cost-effective method of treating psoriasis. This study was supported by grants from Connetics Corporation and National Biologic Corporation.
Conclusion: Alefacept may be an effective and well-tolerated treatment option in patients for whom 3 or more conventional psoriasis treatments are ineffective or inappropriate. This study was originally sponsored by Biogen Idec. Astellas Pharma U.S., Inc. acquired ownership of Amevive effective April 14, 2006 and has subsequently supported the presentation of this study by providing material resources and editorial support.
P2774 Use of extended courses of alefacept in the treatment of moderate-tosevere psoriasis Aditya Gupta, MD, PhD, Mediprobe Research Inc, London, ON, Canada
Vitiligo is a progressive disorder characterized by depigmentation of the epidermis that affects 1% to 2% of the world’s population. Although concomitant presentation of vitiligo with psoriasis is uncommon, several cases have been reported previously in the literature. The etiology of vitiligo is not clear, but it appears to be an autoimmune disease with T-cell involvement. Efalizumab is a T-celletargeted recombinant humanized monoclonal antibody approved for the treatment of adults with chronic moderate to severe plaque psoriasis. Here we describe the case of a patient who presented with vitiligo and psoriasis and was treated with efalizumab to reduce his symptoms of psoriasis. The patient is a 43-year-old Hispanic male whose history includes more than 10 years of vitiligo and more than 5 years of psoriasis. He had been managing his psoriasis with topical steroids. Over the course of his vitiligo and psoriatic disease, he had been treated with numerous therapies, including calcipotriene and topical halobetasol, topical anthralin, topical tazarotene, oral antibiotics, topical steroids of varying strengths, and phototherapy. He switched to treatment with topical tacrolimus followed by oral acitretin when his vitiligo became more prominent in the Spring. He developed pruritus that did not respond to topical corticosteroid treatment. Since progression of vitiligo brought on greater discomfort due to the burning effect of phototherapy, it was appropriate and prudent to shift away from this modality and into the use of a biologic agent such as efalizumab. He initiated efalizumab with a 0.7 mg/kg conditioning dose, and continued thereafter with 1 mg/kg/wk. After 2 months of efalizumab therapy, the pruritus had resolved, scales had disappeared, and plaque elevation had reduced. The patient has remained on efalizumab therapy with no evidence of exacerbation of vitiligo. This case is illustrative of a patient with vitiligo who was treated with efalizumab without adding further complications to his treatment regimen.
Alefacept is an immunosuppressive dimeric fusion protein that interferes with T-lymphocyte activation. This action has been shown in Phase II and III clinical trials to effectively target psoriasis lesions as demonstrated by reduction in the psoriasis area and severity index (PASI) scores during the standard 12-week dosing phase followed by a 12-week follow-up phase. A 75% reduction in PASI score (PASI-75) was found in 28% of subjects during a preliminary 12-week dosing/12-week follow-up. Extension of treatment by providing a second 12-week dosing/12-week follow-up period was studied and showed that PASI-75 was achieved in 40% of subjects, demonstrating that longer dosing periods could improve the efficacy of treatment without compromising patient safety. Similarly, an extended 16-week course of alefacept also showed efficacy and safety, and suggested that extended dosing could be performed without the 12-week follow-up period between dosing phases. Based on this data, an open-label extended dosing study was performed to investigate the efficacy and safety of continuous dosing with alefacept for up to 24 weeks. Subjects with moderate to severe psoriasis were enrolled and provided with a standard 12-week dosing of alefacept. If the subject had not shown a 90% decrease in PASI score (PASI-90) at week 12, dosing was continued until week 16. Similarly, at weeks 16 and 20, subjects continued with weekly dosing if they did not show PASI-90 or greater. All dosing was stopped at week 24, and subjects continued to be followedup to week 28 and week 36. Approximately 25 patients have been enrolled into the trial currently. Initial data shows that for subjects who are beyond week 12, 42% have achieved PASI-75 by week 24, suggesting that continuous dosing provides similar efficacy to extended-pause dosing with similar safety profile. Most subjects continued to require dosing beyond week 16 and 20. One subject achieved PASI-90 at week 16 and discontinued drug use. PASI-90 was maintained to week 36 without further drug use. The mean reduction in PASI score from baseline increased with treatment duration from 18% at week 12, to 40% at week 16, and 54% at week 24. Up to 30 subjects will be followed to week 36 at the end of the trial. This interim data suggests that continuous dosing with alefacept is safe and effective, and a 12-week follow-up phase may not be required before initiating repeat dosing.
Development and production supported by Genentech, Inc.
Partial sponsor: Astellas Canada.
P2772 Efalizumab treatment of a patient presenting with vitiligo and psoriasis Adolfo Fernandez-Obregon, MD, Hudson Dermatology and Skin Cancer Center, Hoboken, NJ, United States
AB192
J AM ACAD DERMATOL
FEBRUARY 2007