Efficacy of multiple courses of alefacept in combination with other psoriasis therapies: a study...
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P590 EFFICACY OF MULTIPLE COURSES OF ALEFACEPT IN COMBINATION WITH OTHER PSORIASIS THERAPIES: A STUDY THAT REFLECTS THE CLINICAL PRAC- TICE SETTING Kenneth Gordon, MD, Loyola University Medical Center, Maywood, IL, United States, Wolfram Sterry, MD, Universitatsklinikum Charite, Berlin, Germany Psoriasis is a chronic, relapsing skin disease that often requires multiple courses of treatment. Alefacept improves psoriasis by selectively targeting the T cells involved in psoriasis pathogenesis. It has been shown to have an encouraging efficacy and safety profile in multiple randomized, placebo-controlled studies and retreatment trials. To understand the best way to manage existing therapies during a course of alefacept, an international study is being conducted under conditions reflective of the clinical practice setting (ie, combining alefacept with other agents). Patients are eligible for enrollment provided they have chronic plaque psoriasis requiring systemic therapy, are at least 16 years of age, have CD4 T-cell counts at or above the lower limit of normal (at least 300 cells/mm3 if on a stable dose of prednisone), and are naı ¨ve to alefacept therapy. Patients may receive up to 3 treatment courses of intramuscular alefacept 15 mg. Each course consists of 12 weekly injections followed by 12 weeks of observation. Retreatment courses of alefacept are provided for patients whose disease has progressed to require systemic therapy and whose CD4 T-cell counts meet the above criteria. In each course, patients are allowed to receive 1 concomitant psoriasis therapy in addition to alefacept. To date, enrolled patients are receiving alefacept in addition to low-potency topicals (31%), high-potency topicals (29%), methotrexate (15%), cyclosporine (12%), ultraviolet B light (6%), systemic retinoids (6%), and prednisone (1%). Methotrexate is being tapered over the first 4 weeks of alefacept therapy. To avoid flares, patients receiving cyclospor- ine must continue such treatment through week 11 of the alefacept dosing period followed by gradual tapering over the following 6 weeks. An objective of this study is to determine the efficacy of initial and repeat courses of alefacept and the duration of response after the first 2 courses in combination regimens. Physician Global Assessment is being used to evaluate efficacy. Circulating total, CD4, and CD8 lymphocyte counts are being measured at various time points throughout the study. All patients who have completed 12 weeks of treatment will be included in the efficacy analysis. Efficacy results will be presented, which should provide valuable insight into the management of other psoriasis therapies when used concurrently with alefacept. Disclosure not available at press time. Sponsored in part by Biogen, Inc. P591 SAFETY OF MULTIPLE COURSES OF ALEFACEPT IN COMBINATION WITH OTHER PSORIASIS THERAPIES: A STUDY THAT REFLECTS THE CLINICAL PRACTICE SET- TING Gerald Krueger, MD, University of Utah Health Sciences Center, Salt Lake City, UT, United States, Peter van de Kerkhof, MD, University Hospital Nijmegen, Nijmegen, Netherlands The chronic and relapsing nature of psoriasis often necessitates multiple courses of treatment. Alefacept improves psoriasis by selectively targeting the T cells involved in psoriasis pathogenesis. Alefacept has demonstrated excellent safety and efficacy in mul- tiple randomized, placebo-controlled studies and retreatment trials. To understand how to optimize the use of alefacept for the treatment of chronic plaque psoriasis, particularly in patients already using other psoriasis therapies, an international study is being con- ducted under conditions reflective of the clinical practice setting (ie, combining alefacept with other agents). To be eligible for enrollment, patients must be at least 16 years of age, require systemic therapy, have CD4 T-cell counts at or above the lower limit of normal (at least 300 cells/mm3 if on a stable dose of prednisone), and be naı ¨ve to alefacept therapy. Patients may receive up to 3 treatment courses of alefacept 15 mg. Each course consists of 12 once-weekly intramuscular injections followed by 12 weeks of observation. Patients are eligible for retreatment courses of alefacept provided their disease has progressed to require systemic therapy and their CD4 T-cell counts meet the above criteria. In each course, patients are allowed to receive 1 concomitant psoriasis therapy in addition to alefacept. To date, in addition to receiving alefacept, approximately 31% of patients are receiving concomitant low-potency topicals, 29% high-potency topicals, 15% methotrexate, 12% cyclosporine, 6% ultraviolet B light, 6% systemic retinoids, and 1% prednisone. Methotrexate is being tapered over the first 4 weeks of alefacept therapy. To avoid flares, patients receiving cyclosporine must continue such treatment through week 11 of the alefacept dosing period followed by gradual tapering over the following 6 weeks. The primary objective of this study is to evaluate the safety of up to 3 courses of alefacept, including assessments of adverse events, infections, selected blood chemistries, physical examinations, and vital signs. All patients who have received at least 1 dose of alefacept will be included in the safety analysis. The safety results, which will be presented, should provide valuable insight into the management of other psoriasis therapies when used concurrently with alefacept. Disclosure not available at press time. Sponsored in part by Biogen, Inc. P592 THE SAFETY OF ALEFACEPT USING A REDUCED SCHEDULE FOR MONITORING T CELLS Richard Langley, MD, Queen Elizabeth II Health Sciences Center, Halifax, NS, Canada, Diane Baker, MD, 1706 NW Glisan Street, Suite 2, Portland, OR, United States, Janet Roberts, MD, Northwest Cutaneous Research Specialists, Portland, OR, United States Alefacept (fully human LFA-3/IgG1 fusion protein) is the first and only biologic agent approved for the treatment of adult patients with chronic plaque psoriasis. Alefacept has a dual mechanism of action that selectively reduces memory (CD45RO) T cells, which have been implicated in the pathogenesis of psoriasis. Because CD4 and CD8 T-cell counts are reduced, routine monitoring is recommended. In the pivotal phase 3 studies of alefacept, T-cell counts were monitored weekly prior to the administration of alefa- cept. Analyses of these studies showed no association between CD4 counts 250 cells/uL and infection, and no opportunistic infections were reported. During the treat- ment phase of these studies, at least one placebo substitution for CD4 counts below 250 cells/uL occurred in 5% and 10% of patients receiving alefacept 15 mg IM and 7.5 mg IV, respectively. As part of ongoing open-label, multicenter, extension studies, the safety of every other week monitoring of T-cell counts is being evaluated. These studies are being conducted in patients who previously received alefacept in the phase 3 studies. Patients can receive up to 3 additional courses of alefacept treatment, either IV or IM, consistent with what they received in the phase 3 studies. A course of therapy is defined as once weekly treatment for 12 weeks followed by 12 weeks of observation. To be eligible for therapy, a patient’s disease must have progressed to require systemic therapy or photo- therapy and their CD4 T-cell count must be at or above the lower limit of normal. Safety and tolerability will be assessed by adverse event reports, infection and malignancy rates, physical exams, monitoring vital signs, and standard laboratory assessments. Changes in lymphocytes and lymphocyte subsets as well as antigenicity will be evaluated. These data will provide important information on the practical use of alefacept in patients with chronic plaque psoriasis. Disclosure not available at press time. Sponsored in part by Biogen, Inc. P593 PILOT TRIAL OF TOPICAL BEXAROTENE GEL IN MILD TO MODERATE PLAQUE PSORIASIS Debra L Breneman, MD, University of Cincinnati, Cincinnati, OH, United States, Pranav Sheth, MD, University of Cincinnati, Cincinnati, OH, United States, Victor Stevens, PhD, Ligand Pharmaceuticals, San Diego, CA, United States To examine the potential activity of bexarotene gel in psoriasis, a phase II open-label pilot study was conducted in 24 patients with moderate plaque psoriasis. Psoriasis is a T-cell driven disease that responds to retinoids. Bexarotene is an RXR-binding molecule that is approved for another T-cell disease, cutaneous T-cell lymphoma. Patients had a median body surface involvement with psoriasis of 9% (range 5-14%). Treatment with bexarotene gel was escalated weekly from QOD to BID, with the option to increase it to QID. Treatment continued for 16 weeks, with the option to continue for 24 weeks for responding patients. The face, scalp, and intertrigenous areas could be treated with a lower frequency of bexarotene gel, could be left untreated, or could be treated with topical hydrocortisone. No other treatments for psoriasis were allowed. Patients were evaluated for efficacy and safety at least every 2 weeks to Week 8 of the study and then every 4 weeks. Efficacy was evaluated by a physician’s global assessment (PGA), the area involved with psoriasis and the severity of erythema, plaque elevation and scaling. Patients evaluated pruritus and their global condition relative to baseline at each visit. Interim results in 18 of 20 patients who were evaluable demonstrated a 67% response rate by the PGA at 50% improvement in disease. Half of responding patients (33%) achieved a 75% clearing of psoriasis. Reductions in the area involved and in severity scores of signs of psoriasis correlated with the improvement assessed by PGA scores. Responding patients evaluated their psoriasis to be between 60-100% improved, and the mean score in itch improved from moderate (4) at baseline to less than mild (1) or none (0) at response. The median time to first response was 4 weeks (range 2-6 weeks). Adverse events consisted primarily of application site irritation, rash, and burning or stinging. These were mild to moderate in severity and reversible after adjusting the treatment frequency regimen. In this study, bexarotene gel was demonstrated to be efficacious and well-tolerated in treating psoriasis for most patients. Bexarotene gel may be useful as an alternative therapy for mild to moderate psoriasis. Victor Stevens is an employee of Ligand Pharmaceuticals. 100% is sponsored by Ligand Pharmaceuticals. P152 JAM ACAD DERMATOL MARCH 2004
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Transcript of Efficacy of multiple courses of alefacept in combination with other psoriasis therapies: a study...
P590EFFICACY OF MULTIPLE COURSES OF ALEFACEPT IN COMBINATION WITHOTHER PSORIASIS THERAPIES: A STUDY THAT REFLECTS THE CLINICAL PRAC-TICE SETTINGKenneth Gordon, MD, Loyola University Medical Center, Maywood, IL, United States,Wolfram Sterry, MD, Universitatsklinikum Charite, Berlin, Germany
Psoriasis is a chronic, relapsing skin disease that often requires multiple courses oftreatment. Alefacept improves psoriasis by selectively targeting the T cells involved inpsoriasis pathogenesis. It has been shown to have an encouraging efficacy and safetyprofile in multiple randomized, placebo-controlled studies and retreatment trials. Tounderstand the best way to manage existing therapies during a course of alefacept, aninternational study is being conducted under conditions reflective of the clinical practicesetting (ie, combining alefacept with other agents). Patients are eligible for enrollmentprovided they have chronic plaque psoriasis requiring systemic therapy, are at least 16years of age, have CD4� T-cell counts at or above the lower limit of normal (at least 300cells/mm3 if on a stable dose of prednisone), and are naı̈ve to alefacept therapy. Patientsmay receive up to 3 treatment courses of intramuscular alefacept 15 mg. Each courseconsists of 12 weekly injections followed by 12 weeks of observation. Retreatmentcourses of alefacept are provided for patients whose disease has progressed to requiresystemic therapy and whose CD4� T-cell counts meet the above criteria. In each course,patients are allowed to receive 1 concomitant psoriasis therapy in addition to alefacept.To date, enrolled patients are receiving alefacept in addition to low-potency topicals(31%), high-potency topicals (29%), methotrexate (15%), cyclosporine (12%), ultravioletB light (6%), systemic retinoids (6%), and prednisone (1%). Methotrexate is being taperedover the first 4 weeks of alefacept therapy. To avoid flares, patients receiving cyclospor-ine must continue such treatment through week 11 of the alefacept dosing periodfollowed by gradual tapering over the following 6 weeks. An objective of this study is todetermine the efficacy of initial and repeat courses of alefacept and the duration ofresponse after the first 2 courses in combination regimens. Physician Global Assessmentis being used to evaluate efficacy. Circulating total, CD4�, and CD8� lymphocyte countsare being measured at various time points throughout the study. All patients who havecompleted 12 weeks of treatment will be included in the efficacy analysis. Efficacy resultswill be presented, which should provide valuable insight into the management of otherpsoriasis therapies when used concurrently with alefacept.
Disclosure not available at press time.
Sponsored in part by Biogen, Inc.
P591SAFETY OF MULTIPLE COURSES OF ALEFACEPT IN COMBINATION WITH OTHERPSORIASIS THERAPIES: A STUDY THAT REFLECTS THE CLINICAL PRACTICE SET-TINGGerald Krueger, MD, University of Utah Health Sciences Center, Salt Lake City, UT, UnitedStates, Peter van de Kerkhof, MD, University Hospital Nijmegen, Nijmegen, Netherlands
The chronic and relapsing nature of psoriasis often necessitates multiple courses oftreatment. Alefacept improves psoriasis by selectively targeting the T cells involved inpsoriasis pathogenesis. Alefacept has demonstrated excellent safety and efficacy in mul-tiple randomized, placebo-controlled studies and retreatment trials. To understand howto optimize the use of alefacept for the treatment of chronic plaque psoriasis, particularlyin patients already using other psoriasis therapies, an international study is being con-ducted under conditions reflective of the clinical practice setting (ie, combining alefaceptwith other agents). To be eligible for enrollment, patients must be at least 16 years of age,require systemic therapy, have CD4� T-cell counts at or above the lower limit of normal(at least 300 cells/mm3 if on a stable dose of prednisone), and be naı̈ve to alefacepttherapy. Patients may receive up to 3 treatment courses of alefacept 15 mg. Each courseconsists of 12 once-weekly intramuscular injections followed by 12 weeks of observation.Patients are eligible for retreatment courses of alefacept provided their disease hasprogressed to require systemic therapy and their CD4� T-cell counts meet the abovecriteria. In each course, patients are allowed to receive 1 concomitant psoriasis therapyin addition to alefacept. To date, in addition to receiving alefacept, approximately 31% ofpatients are receiving concomitant low-potency topicals, 29% high-potency topicals, 15%methotrexate, 12% cyclosporine, 6% ultraviolet B light, 6% systemic retinoids, and 1%prednisone. Methotrexate is being tapered over the first 4 weeks of alefacept therapy. Toavoid flares, patients receiving cyclosporine must continue such treatment through week11 of the alefacept dosing period followed by gradual tapering over the following 6weeks. The primary objective of this study is to evaluate the safety of up to 3 courses ofalefacept, including assessments of adverse events, infections, selected blood chemistries,physical examinations, and vital signs. All patients who have received at least 1 dose ofalefacept will be included in the safety analysis. The safety results, which will bepresented, should provide valuable insight into the management of other psoriasistherapies when used concurrently with alefacept.
Disclosure not available at press time.
Sponsored in part by Biogen, Inc.
P592THE SAFETY OF ALEFACEPT USING A REDUCED SCHEDULE FOR MONITORING TCELLSRichard Langley, MD, Queen Elizabeth II Health Sciences Center, Halifax, NS, Canada,Diane Baker, MD, 1706 NW Glisan Street, Suite 2, Portland, OR, United States, JanetRoberts, MD, Northwest Cutaneous Research Specialists, Portland, OR, United States
Alefacept (fully human LFA-3/IgG1 fusion protein) is the first and only biologic agentapproved for the treatment of adult patients with chronic plaque psoriasis. Alefacept hasa dual mechanism of action that selectively reduces memory (CD45RO�) T cells, whichhave been implicated in the pathogenesis of psoriasis. Because CD4� and CD8� T-cellcounts are reduced, routine monitoring is recommended. In the pivotal phase 3 studiesof alefacept, T-cell counts were monitored weekly prior to the administration of alefa-cept. Analyses of these studies showed no association between CD4� counts �250cells/uL and infection, and no opportunistic infections were reported. During the treat-ment phase of these studies, at least one placebo substitution for CD4� counts below 250cells/uL occurred in 5% and 10% of patients receiving alefacept 15 mg IM and 7.5 mg IV,respectively. As part of ongoing open-label, multicenter, extension studies, the safety ofevery other week monitoring of T-cell counts is being evaluated. These studies are beingconducted in patients who previously received alefacept in the phase 3 studies. Patientscan receive up to 3 additional courses of alefacept treatment, either IV or IM, consistentwith what they received in the phase 3 studies. A course of therapy is defined as onceweekly treatment for 12 weeks followed by 12 weeks of observation. To be eligible fortherapy, a patient’s disease must have progressed to require systemic therapy or photo-therapy and their CD4� T-cell count must be at or above the lower limit of normal. Safetyand tolerability will be assessed by adverse event reports, infection and malignancy rates,physical exams, monitoring vital signs, and standard laboratory assessments. Changes inlymphocytes and lymphocyte subsets as well as antigenicity will be evaluated. These datawill provide important information on the practical use of alefacept in patients withchronic plaque psoriasis.
Disclosure not available at press time.
Sponsored in part by Biogen, Inc.
P593PILOT TRIAL OF TOPICAL BEXAROTENE GEL IN MILD TO MODERATE PLAQUEPSORIASISDebra L Breneman, MD, University of Cincinnati, Cincinnati, OH, United States, PranavSheth, MD, University of Cincinnati, Cincinnati, OH, United States, Victor Stevens, PhD,Ligand Pharmaceuticals, San Diego, CA, United States
To examine the potential activity of bexarotene gel in psoriasis, a phase II open-label pilotstudy was conducted in 24 patients with moderate plaque psoriasis. Psoriasis is a T-celldriven disease that responds to retinoids. Bexarotene is an RXR-binding molecule that isapproved for another T-cell disease, cutaneous T-cell lymphoma. Patients had a medianbody surface involvement with psoriasis of 9% (range 5-14%). Treatment with bexarotenegel was escalated weekly from QOD to BID, with the option to increase it to QID.Treatment continued for 16 weeks, with the option to continue for 24 weeks forresponding patients. The face, scalp, and intertrigenous areas could be treated with alower frequency of bexarotene gel, could be left untreated, or could be treated withtopical hydrocortisone. No other treatments for psoriasis were allowed. Patients wereevaluated for efficacy and safety at least every 2 weeks to Week 8 of the study and thenevery 4 weeks. Efficacy was evaluated by a physician’s global assessment (PGA), the areainvolved with psoriasis and the severity of erythema, plaque elevation and scaling.Patients evaluated pruritus and their global condition relative to baseline at each visit.Interim results in 18 of 20 patients who were evaluable demonstrated a 67% response rateby the PGA at �50% improvement in disease. Half of responding patients (33%) achieveda �75% clearing of psoriasis. Reductions in the area involved and in severity scores ofsigns of psoriasis correlated with the improvement assessed by PGA scores. Respondingpatients evaluated their psoriasis to be between 60-100% improved, and the mean scorein itch improved from moderate (4) at baseline to less than mild (1) or none (0) atresponse. The median time to first response was 4 weeks (range 2-6 weeks). Adverseevents consisted primarily of application site irritation, rash, and burning or stinging.These were mild to moderate in severity and reversible after adjusting the treatmentfrequency regimen. In this study, bexarotene gel was demonstrated to be efficacious andwell-tolerated in treating psoriasis for most patients. Bexarotene gel may be useful as analternative therapy for mild to moderate psoriasis.
Victor Stevens is an employee of Ligand Pharmaceuticals.
100% is sponsored by Ligand Pharmaceuticals.
P152 J AM ACAD DERMATOL MARCH 2004
