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A simple algorithm for reduced lymphocyte monitoring with alefacept therapy
P2710
P2712
A SAFE AND EFFECTIVE STRATEGY FOR TRANSITIONING PATIENTS WITH PSORIASIS FROM CYCLOSPORINE TO ALEFACEPT THERAPY Melissa Magliocco, MD, Ann Marie Lozano, RN, Claudia Van Saders, RN, Alice Gottlieb, MD, PhD, University of Medicine and Dentistry of New JerseyeRobert Wood Johnson Medical School, New Brunswick, NJ, United States
ACITRETIN IN COMBINATION WITH HOME BROADBAND ULTRAVIOLET LIGHT AS A PSORIASIS TREATMENT Daniel Pearce, MD, Steven Feldman, MD, PhD, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, United States
Cyclosporine is a frequently used systemic agent in the treatment of moderate to severe chronic plaque psoriasis. However, its long-term use is limited by safety concerns that include major organ system toxicities. Targeted biologic therapies, such as alefacept, offer patients with psoriasis new treatment options. In clinical practice, an effective and safe strategy is necessary to transition patients receiving treatment with cyclosporine to alefacept therapy. An open-label study has been initiated to examine a strategy that involves tapering doses of cyclosporine during alefacept treatment in up to 20 patients with psoriasis. The study consists of 3 phases. Phase 1 (weeks 1-12) involves initiation of alefacept treatment (15 mg once weekly by intramuscular injection) while tapering down the dose of cyclosporine to 2.5 mg/kg per day. Topical therapy is permitted in phase 1. In phase 2 (weeks 13-24), patients discontinue both alefacept and cyclosporine. Patients are allowed to receive topical therapy or UVB phototherapy as per physician’s standard of care. In phase 3 (weeks 25-48), patients receive a second course of alefacept followed by 12 weeks of observation. Topical therapy is permitted throughout phase 3, and UVB phototherapy is allowed during the observation period after the 12-week alefacept treatment is complete. Cyclosporine is not administered in phases 2 or 3. Assessments include physician global assessment (PGA), lymphocyte subset analysis, adverse events, and laboratory tests as specified in the product labeling for alefacept and cyclosporine. To date, 11 patients have been enrolled, with a median age of 48 years and a median duration of disease of 21 years. Four patients are in phase 1, 3 patients are in phase 2, and 4 patients are in phase 3 of the study. For the 7 patients who have completed phase 1 of the study and for the 2 patients who have received 8 weeks or more of alefacept treatment in phase 1, PGA scores remained stable and CD4+ T-cell counts remained higher than 250 cells/mm3 during the dose tapering of cyclosporine. No flares or rebound of psoriasis have been observed. Adverse events are consistent with those observed with either product used alone. Preliminary results from these patients suggest that alefacept does not worsen the renal toxicity associated with cyclosporine and that cyclosporine does not interfere with the mechanism of action of alefacept.
Dr. Feldman has been a speaker for Connetics Corporation Supported by National Biologics Co. and Connetics Corporation.
Psoriasis is a common, chronic, immune-mediated disease with a profound impact on health and quality of life. The treatment of psoriasis is complex at times because of the disease’s characteristics and the cumbersome treatments. Combination regimens are the standard of care and are particularly useful in patients with moderate to severe disease as they provide enhanced efficacy and minimize the potential for adverse events. Acitretin and ultraviolet (UV) light are two therapies that are approved for psoriasis; when used together this regimen has efficacy similar to some of the best available treatments. Office-based phototherapy is difficult for all but a minority of patients, whereas UV light administered by devices in the home may be feasible. We plan to present efficacy and short-term safety data from a multicenter clinical trial using home phototherapy in combination with acitretin for plaque-type psoriasis. We believe that the combination of acitretin and homebased phototherapy will provide a convenient, cost-effective method of treating psoriasis.
Dr. Gottlieb is a clinical investigator and consultant for Biogen Idec, Inc. Supported by Biogen Idec Inc.
P2713
P2711 A SIMPLE ALGORITHM FOR REDUCED LYMPHOCYTE MONITORING WITH ALEFACEPT THERAPY Barry Ticho, MD, PhD, Carmen Bozic, MD, Biogen Idec, Cambridge, MA, United States; Jennifer Cather, MD, Texas Dermatology Associates, Dallas, TX, United States Alefacept, the first biologic agent approved for patients with moderate to severe chronic plaque psoriasis, has a dual mechanism of action that selectively reduces memory T cells. Because CD4+ and CD8+ T-cell counts are reduced, routine monitoring is recommended. In phase 3 studies of alefacept, T-cell counts were monitored weekly during alefacept administration. Analyses of these studies showed no association between CD4+ counts less than 250 cells/mm3 and infection, and no opportunistic infections were reported. During the treatment phase of these studies, at least one placebo substitution for CD4+ counts less than 250 cells/mm3 occurred in 4% and 10% of patients receiving alefacept 15 mg intramuscularly and 7.5 mg intravenously, respectively. Since the pivotal phase 3 studies, more than 1000 patients have had T-cell counts monitored every other week in several studies of alefacept. These studies have shown that the adverse event profile with every other week T-cell monitoring is similar to that observed with weekly monitoring. In addition, reductions in CD4+ T-cell counts during alefacept dosing were similar with weekly and every other week monitoring. Mathematical modeling of phase 2 and 3 data on CD4+ T-cell effects during alefacept treatment was conducted to further support a reduced monitoring schedule. A simulation of 50,000 subjects was used to identify a threshold CD4 level (either at baseline or subsequent to dosing) above which 99% or more of patients would not have counts less than 250 cells/mm3 during subsequent dosing. With intramuscular alefacept, 99.7% of patients with CD4+ counts higher than 400 cells/mm3 at week 4 maintained counts higher than 250 cells/mm3. In addition, more than 99.9% of patients with CD4+ counts higher than 600 cells/mm3 at week 4 maintained counts of more than 250 cells/mm3. Thus these findings suggest the following T-cell monitoring algorithm for patients treated with alefacept: At week 4, if the CD4+ count is more than 600 cells/mm3, no further monitoring for the remainder of the dosing period is necessary; if the CD4+ count is between 400 and 600 cells/mm3, monthly monitoring is recommended; and if the CD4+ count is less than 400 cells/mm3, every other week monitoring should be continued. These data suggest that the CD4+ T-cell count changes associated with alefacept are consistent and predictable. Drs. Ticho and Bozic are employees of Biogen Idec, Inc. Dr. Cather is a clinical investigator and consultant for Biogen Idec, Inc. Supported by Biogen Idec Inc.
P174
J AM ACAD DERMATOL
ADALIMUMAB EFFICACY AND SAFETY RESULTS IN PATIENTS WITH MODERATE TO SEVERE CHRONIC PLAQUE PSORIASIS WITH AND WITHOUT PSORIATIC ARTHRITIS M. Alan Menter, MD, Texas Dermatology Research Institute, Dallas, TX, United States; Kenneth Gordon, MD, Loyola University Medical Center, Maywood, IL, United States; Craig Leonardi, MD, Central Dermatology Inc., St. Louis, MO, United States; Diana Chen, MD, Abbott Laboratories, Abbott Park, IL, United States Background: Adalimumab is a fully human monoclonal antibody that targets tumor necrosis factor (TNF). TNF expression is increased in psoriatic plaques and psoriatic joints. Objective: To evaluate the efficacy of adalimumab in patients with moderate to severe chronic plaque psoriasis with and without psoriatic arthritis (PsA). Methods: Data were collected from a 12-week, randomized, double-blind, placebocontrolled, phase II trial and from the first 12 weeks (blinded) of a 48-week extension trial conducted in the United States and Canada. Adult patients with moderate to severe chronic plaque psoriasis for 1 year or longer and an affected body surface area (BSA) of 5% or more were randomized to receive subcutaneous injections of (1) 80-mg adalimumab at week 0 followed by 40-mg adalimumab every other week (eow) beginning at week 1; (2) 80-mg adalimumab at weeks 0 and 1, followed by 40-mg weekly at week 2; or (3) placebo. Before entry, investigators identified patients with PsA by obtaining medical histories and providing dates of PsA onset. Results: A total of 148 patients entered; 43 (29%) had PsA. The PsA subgroup was predominately male (63%) and Caucasian (95%) with a mean age of 46 years (range 23-86 years). PsA patients had a mean duration of psoriasis of 21 years, a mean duration of PsA of 10 years, a mean baseline PASI score of 17.6, and a mean percentage of BSA affected of 28.7%. Patients without PsA had similar baseline demographics and moderate to severe psoriasis at study entry. The percentages of patients with PsA who achieved PASI 75 responses at week 12 were 46.7% for the 40mg eow group and 58.3% for the 40-mg weekly group (P \ .01 and P \ .001 vs. placebo, respectively). For patients without PsA, 56.7% in the eow dose group achieved PASI 75 at week 12 and 86.8% in the weekly dose group (P \ .001 vs. placebo for both). At week 24, 53.3% and 58.3% of patients with PsA in the eow and weekly dose groups, respectively, reached PASI 75. For those without PsA, 70% and 76.3% in the eow and weekly dose groups, respectively, reached PASI 75 at week 24. In addition, the percentages of all patients with at least one adverse event were comparable among the treatment groups: 67% for placebo, 62% for adalimumab 40 mg eow, and 78% for adalimumab 40 mg weekly. Conclusions: These data show that adalimumab is similarly efficacious in treating moderate to severe plaque psoriasis in patients with and without PsA. Adalimumab is safe and well tolerated in the treatment of psoriasis. Drs. Menter, Gordon, and Leonardi are primary investigators for Abbott Laboratories. 100% sponsored by Abbott Laboratories
MARCH 2005
P2712
A SAFE AND EFFECTIVE STRATEGY FOR TRANSITIONING PATIENTS WITH PSORIASIS FROM CYCLOSPORINE TO ALEFACEPT THERAPY Melissa Magliocco, MD, Ann Marie Lozano, RN, Claudia Van Saders, RN, Alice Gottlieb, MD, PhD, University of Medicine and Dentistry of New JerseyeRobert Wood Johnson Medical School, New Brunswick, NJ, United States
ACITRETIN IN COMBINATION WITH HOME BROADBAND ULTRAVIOLET LIGHT AS A PSORIASIS TREATMENT Daniel Pearce, MD, Steven Feldman, MD, PhD, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, United States
Cyclosporine is a frequently used systemic agent in the treatment of moderate to severe chronic plaque psoriasis. However, its long-term use is limited by safety concerns that include major organ system toxicities. Targeted biologic therapies, such as alefacept, offer patients with psoriasis new treatment options. In clinical practice, an effective and safe strategy is necessary to transition patients receiving treatment with cyclosporine to alefacept therapy. An open-label study has been initiated to examine a strategy that involves tapering doses of cyclosporine during alefacept treatment in up to 20 patients with psoriasis. The study consists of 3 phases. Phase 1 (weeks 1-12) involves initiation of alefacept treatment (15 mg once weekly by intramuscular injection) while tapering down the dose of cyclosporine to 2.5 mg/kg per day. Topical therapy is permitted in phase 1. In phase 2 (weeks 13-24), patients discontinue both alefacept and cyclosporine. Patients are allowed to receive topical therapy or UVB phototherapy as per physician’s standard of care. In phase 3 (weeks 25-48), patients receive a second course of alefacept followed by 12 weeks of observation. Topical therapy is permitted throughout phase 3, and UVB phototherapy is allowed during the observation period after the 12-week alefacept treatment is complete. Cyclosporine is not administered in phases 2 or 3. Assessments include physician global assessment (PGA), lymphocyte subset analysis, adverse events, and laboratory tests as specified in the product labeling for alefacept and cyclosporine. To date, 11 patients have been enrolled, with a median age of 48 years and a median duration of disease of 21 years. Four patients are in phase 1, 3 patients are in phase 2, and 4 patients are in phase 3 of the study. For the 7 patients who have completed phase 1 of the study and for the 2 patients who have received 8 weeks or more of alefacept treatment in phase 1, PGA scores remained stable and CD4+ T-cell counts remained higher than 250 cells/mm3 during the dose tapering of cyclosporine. No flares or rebound of psoriasis have been observed. Adverse events are consistent with those observed with either product used alone. Preliminary results from these patients suggest that alefacept does not worsen the renal toxicity associated with cyclosporine and that cyclosporine does not interfere with the mechanism of action of alefacept.
Dr. Feldman has been a speaker for Connetics Corporation Supported by National Biologics Co. and Connetics Corporation.
Psoriasis is a common, chronic, immune-mediated disease with a profound impact on health and quality of life. The treatment of psoriasis is complex at times because of the disease’s characteristics and the cumbersome treatments. Combination regimens are the standard of care and are particularly useful in patients with moderate to severe disease as they provide enhanced efficacy and minimize the potential for adverse events. Acitretin and ultraviolet (UV) light are two therapies that are approved for psoriasis; when used together this regimen has efficacy similar to some of the best available treatments. Office-based phototherapy is difficult for all but a minority of patients, whereas UV light administered by devices in the home may be feasible. We plan to present efficacy and short-term safety data from a multicenter clinical trial using home phototherapy in combination with acitretin for plaque-type psoriasis. We believe that the combination of acitretin and homebased phototherapy will provide a convenient, cost-effective method of treating psoriasis.
Dr. Gottlieb is a clinical investigator and consultant for Biogen Idec, Inc. Supported by Biogen Idec Inc.
P2713
P2711 A SIMPLE ALGORITHM FOR REDUCED LYMPHOCYTE MONITORING WITH ALEFACEPT THERAPY Barry Ticho, MD, PhD, Carmen Bozic, MD, Biogen Idec, Cambridge, MA, United States; Jennifer Cather, MD, Texas Dermatology Associates, Dallas, TX, United States Alefacept, the first biologic agent approved for patients with moderate to severe chronic plaque psoriasis, has a dual mechanism of action that selectively reduces memory T cells. Because CD4+ and CD8+ T-cell counts are reduced, routine monitoring is recommended. In phase 3 studies of alefacept, T-cell counts were monitored weekly during alefacept administration. Analyses of these studies showed no association between CD4+ counts less than 250 cells/mm3 and infection, and no opportunistic infections were reported. During the treatment phase of these studies, at least one placebo substitution for CD4+ counts less than 250 cells/mm3 occurred in 4% and 10% of patients receiving alefacept 15 mg intramuscularly and 7.5 mg intravenously, respectively. Since the pivotal phase 3 studies, more than 1000 patients have had T-cell counts monitored every other week in several studies of alefacept. These studies have shown that the adverse event profile with every other week T-cell monitoring is similar to that observed with weekly monitoring. In addition, reductions in CD4+ T-cell counts during alefacept dosing were similar with weekly and every other week monitoring. Mathematical modeling of phase 2 and 3 data on CD4+ T-cell effects during alefacept treatment was conducted to further support a reduced monitoring schedule. A simulation of 50,000 subjects was used to identify a threshold CD4 level (either at baseline or subsequent to dosing) above which 99% or more of patients would not have counts less than 250 cells/mm3 during subsequent dosing. With intramuscular alefacept, 99.7% of patients with CD4+ counts higher than 400 cells/mm3 at week 4 maintained counts higher than 250 cells/mm3. In addition, more than 99.9% of patients with CD4+ counts higher than 600 cells/mm3 at week 4 maintained counts of more than 250 cells/mm3. Thus these findings suggest the following T-cell monitoring algorithm for patients treated with alefacept: At week 4, if the CD4+ count is more than 600 cells/mm3, no further monitoring for the remainder of the dosing period is necessary; if the CD4+ count is between 400 and 600 cells/mm3, monthly monitoring is recommended; and if the CD4+ count is less than 400 cells/mm3, every other week monitoring should be continued. These data suggest that the CD4+ T-cell count changes associated with alefacept are consistent and predictable. Drs. Ticho and Bozic are employees of Biogen Idec, Inc. Dr. Cather is a clinical investigator and consultant for Biogen Idec, Inc. Supported by Biogen Idec Inc.
P174
J AM ACAD DERMATOL
ADALIMUMAB EFFICACY AND SAFETY RESULTS IN PATIENTS WITH MODERATE TO SEVERE CHRONIC PLAQUE PSORIASIS WITH AND WITHOUT PSORIATIC ARTHRITIS M. Alan Menter, MD, Texas Dermatology Research Institute, Dallas, TX, United States; Kenneth Gordon, MD, Loyola University Medical Center, Maywood, IL, United States; Craig Leonardi, MD, Central Dermatology Inc., St. Louis, MO, United States; Diana Chen, MD, Abbott Laboratories, Abbott Park, IL, United States Background: Adalimumab is a fully human monoclonal antibody that targets tumor necrosis factor (TNF). TNF expression is increased in psoriatic plaques and psoriatic joints. Objective: To evaluate the efficacy of adalimumab in patients with moderate to severe chronic plaque psoriasis with and without psoriatic arthritis (PsA). Methods: Data were collected from a 12-week, randomized, double-blind, placebocontrolled, phase II trial and from the first 12 weeks (blinded) of a 48-week extension trial conducted in the United States and Canada. Adult patients with moderate to severe chronic plaque psoriasis for 1 year or longer and an affected body surface area (BSA) of 5% or more were randomized to receive subcutaneous injections of (1) 80-mg adalimumab at week 0 followed by 40-mg adalimumab every other week (eow) beginning at week 1; (2) 80-mg adalimumab at weeks 0 and 1, followed by 40-mg weekly at week 2; or (3) placebo. Before entry, investigators identified patients with PsA by obtaining medical histories and providing dates of PsA onset. Results: A total of 148 patients entered; 43 (29%) had PsA. The PsA subgroup was predominately male (63%) and Caucasian (95%) with a mean age of 46 years (range 23-86 years). PsA patients had a mean duration of psoriasis of 21 years, a mean duration of PsA of 10 years, a mean baseline PASI score of 17.6, and a mean percentage of BSA affected of 28.7%. Patients without PsA had similar baseline demographics and moderate to severe psoriasis at study entry. The percentages of patients with PsA who achieved PASI 75 responses at week 12 were 46.7% for the 40mg eow group and 58.3% for the 40-mg weekly group (P \ .01 and P \ .001 vs. placebo, respectively). For patients without PsA, 56.7% in the eow dose group achieved PASI 75 at week 12 and 86.8% in the weekly dose group (P \ .001 vs. placebo for both). At week 24, 53.3% and 58.3% of patients with PsA in the eow and weekly dose groups, respectively, reached PASI 75. For those without PsA, 70% and 76.3% in the eow and weekly dose groups, respectively, reached PASI 75 at week 24. In addition, the percentages of all patients with at least one adverse event were comparable among the treatment groups: 67% for placebo, 62% for adalimumab 40 mg eow, and 78% for adalimumab 40 mg weekly. Conclusions: These data show that adalimumab is similarly efficacious in treating moderate to severe plaque psoriasis in patients with and without PsA. Adalimumab is safe and well tolerated in the treatment of psoriasis. Drs. Menter, Gordon, and Leonardi are primary investigators for Abbott Laboratories. 100% sponsored by Abbott Laboratories
MARCH 2005