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IV clinical trial in patients from Latin America
P2670
P2672
Efficacy of efalizumab for the treatment of moderate to severe plaque psoriasis: A prospective, 24-week, open-label phase IIIb/IV clinical trial in patients from Latin America Fernando M. Stengel, MD, Instituto Universitario Cemic, Buenos Aires, Argentina; Edgardo Chouela, MD, PhD, Hospital Cosme Argerich, Universidad de Buenos Aires, Buenos Aires, Argentina; Maria Denise Fonseca Takahashi, Faculdade de Medicina de USP (Hospital das Clinicas), Sao Paulo, Brazil; Mario Amaya, Hospital de Especialidadaes, IMSS, Monterrey NL, Mexico
Topical clobetasol propionate spray is effective for the treatment of patients with moderate to severe plaque psoriasis already on a stable, ongoing treatment regimen Steven Feldman, MD, PhD, Wake Forest University -School of Medicine, WinstonSalem, NC, United States
Objectives: Efalizumab, a recombinant humanized monoclonal IgG1 antibody against CD11a, inhibits key T-cell mediated processes central to psoriasis pathogenesis. Efalizumab is approved for the treatment of adults with moderate to severe chronic plaque psoriasis in more than 50 countries worldwide. This study analyzed the efficacy and safety of efalizumab in Latin American patients with moderate to severe plaque psoriasis. Efficacy results are reported here; safety results are presented separately. Methods: In this 24-week, open-label, single-arm phase IIIb/IV trial, adults ($18 yrs of age) with moderate to severe plaque psoriasis (body surface area $10%) who were candidates for systemic therapy received efalizumab subcutaneously once a week for 24 weeks (0.7 mg/kg conditioning dose and 1 mg/kg/wk thereafter). Efficacy was assessed via: (1) percentage of patients with Physician’s Global Assessment (PGA) of ‘‘excellent’’ (75-99% improvement) or ‘‘cleared’’ (100% improvement) at week 24; (2) percentage of patients with at least good disease control at week 24 defined by Psoriasis Area and Severity Index (PASI) \8 (or 50% reduction in PASI); Dermatology Life Quality Index (DLQI) \6; and no serious adverse events (SAEs), no treatment-related severe adverse events (AEs), or early study withdrawal; (3) assessment of PASI-75 ($75% reduction vs. baseline) and PASI50 ($50% reduction vs. baseline) response rates. Additional endpoints reported elsewhere included changes over time in PASI, Nail Psoriasis Severity Index, Palmoplantar Pustular Psoriasis Area and Severity Index, Psoriasis Scalp Severity Index, DLQI, and SF-36 Health Survey. Statistical analysis was performed on the intent-to-treat (ITT) population, using nonresponder imputation (NRI; missing ¼ nonresponders), and the last observation carried forward (LOCF) for missing data. Results: In total, 189 patients from 24 centers (Argentina, n ¼ 47; Brazil, n ¼ 81; Mexico, n ¼ 61) were included in the ITT population. Most patients (72.5%, 137/189) completed treatment. At week 24, 46.0% (NRI) and 48.7% (LOCF) of the ITT population achieved a PGA score of ‘‘excellent’’ or ‘‘cleared.’’ The percentage of patients achieving a PASI 75 or PASI 50 response at week 24 was 44.4% and 61.9%, respectively, with NRI.
Patients with psoriasis are often frustrated with their treatment. Patients may fail to clear with topical or even potent systemic agents. A phase IV, multicenter, openlabel trial of 4 weeks of twice daily clobetasol propionate 0.05% spray added on to stable existing systemic or topical therapies was conducted in 731 patients with moderate to severe plaque psoriasis (involving between 3% and 20% BSA). Systemic therapies must have been initiated at least 3 months before starting this study and topical therapies must have been initiated at least 1 month before starting this study. Primary efficacy outcomes included change in target plaque severity and investigator global assessment of improvement. Treatment success was defined as a rating of clear or almost clear or improvement by at least 2 points on the 6-point target plaque severity scale. Tolerability, adverse events and subject assessments were also included. Target plaque severity success was seen in 59% of patients at week 2 and 80% of patients at week 4. Furthermore, 41% were clear or almost clear at week 2 and 70% were clear or almost clear at week 4. At weeks 2 and 4, 27% and 62% of patients, respectively, were globally clear or almost clear. Pruritus and dryness were the most common side effects, reported in 6% and 5% of patients, respectively. A total of 74 adverse events were reported, of which 34 were determined to be possibly, probably, or definitely related to the study medication. Of these, 1 case of atrophy occurred and was considered to be probably related to treatment. The development of a non-messy clobetasol propionate spray preparation facilitates patients’ use of the medication. The product is highly and rapidly effective in patients with moderate to severe psoriasis even when they are already on an ongoing, stable treatment regimen. Study and poster support provided by Galderma Laboratories, L.P.
Conclusions: The efficacy results observed in Latin American patients with moderate to severe plaque psoriasis confirm those obtained in previous efalizumab clinical trials conducted in Europe and North America. 100% supported by Genentech, Inc.
P2671 Use of extended courses of alefacept in the treatment of moderate to severe psoriasis Aditya Gupta, MD, PhD, MBA, Mediprobe Research Inc., London, ON, Canada
P2673 Successful treatment of psoriasis with alefacept in patients with previous adverse reactions to anti-TNFa treatments: Three case studies Tiffani Hamilton, MD, Atlanta Dermatology, Vein & Research Center, Alpharetta, GA, United States
Introduction: Alefacept is an immunosuppressive dimeric fusion protein that interferes with T-lymphocyte activation. Results from phase II/III clinical trials indicate alefacept given in an FDA-approved 12-week dosing/12-week follow-up regimen provides a 75% reduction in psoriasis area and severity index (PASI) score (PASI 75) in 28% of subjects with moderate to severe plaque psoriasis. Extended use regimens of alefacept have shown that longer dosing regimens (up to 16 weeks) can increase the efficacy without compromising patient safety. Objectives: An open-label, single-center, extended-dosing study is being performed to investigate the safety and efficacy of continuous dosing with alefacept for up to 24 weeks for subjects with moderate to severe plaque psoriasis. Methods: All subjects with moderate to severe chronic plaque psoriasis receive an initial 12-week treatment course of alefacept 15 mg IM. Subjects failing to achieve a 90% decrease in PASI score (PASI 90) at week 12 continue to receive up to 12 additional weekly doses of alefacept with further evaluation at weeks 16, 20, and 24. Alefacept dosing will be discontinued in subjects achieving a PASI 90 score or higher at weeks 16 or 20. At the end of the treatment phase, subjects are followed for an additional 12 weeks. Results: To date, 30 subjects have completed the initial 12-week dosing of alefacept, of which 27 subjects have completed the consecutive 12-week dosing period. One subject achieved PASI 90 at week 16; PASI 90 was maintained to week 36 without further drug use in this subject. The mean percent reduction in PASI score from baseline increased with treatment duration from 27.3% at week 12, to 43.6% at week 16, and 55.2% at week 24. At week 24, 33.3% (9/27) achieved PASI-75 or higher. Of the 16 subjects who have completed the 12-week follow-up period, 43.8% (7/16) of subjects continued to improve from week 24 to week 36. One subject maintained a 64% reduction in PASI from week 24 to week 36 without further treatment. No safety issues have been noted with this extended-dosing regimen. Conclusions: This interim data suggests that continuous dosing with alefacept up to 24 weeks is safe and effective.
Conclusions: Alefacept is effective and safe in treating these 3 patients with psoriasis for whom prior treatments with anti-TNFa drugs were unsuccessful or complicated by adverse events. Thus alefacept could be considered for treating patients with psoriasis for whom anti-TNFa drugs are not an option.
Supported by Astellas Pharma Canada Inc.
Supported by Astellas Pharma US, Inc.
FEBRUARY 2008
Rationale and goal: Biologic drugs have been shown to be effective in treating psoriasis. However, treatment with anti-TNFa drugs can cause rebound effects on stoppage and may even induce psoriasis. The objective of these case studies was to evaluate the efficacy and safety of alefacept, a T-cell agent, in treating patients with psoriasis for whom anti-TNFa therapies were unsuccessful. Case 1: A 56-year-old female with a 15-year history of psoriasis and worsening disease after a 6-month course of etanercept was enrolled in a trial evaluating infliximab. However, she continued to worsen as the trial progressed with her disease body surface area (BSA) increasing to 50% (baseline BSA ¼ 12%) during the open label portion and thus was discontinued from the study. Subsequently, treatment with two 12-week courses of alefacept resulted in decrease in her disease BSA to 2%. Case 2: A 37-year-old black male with a 12-year history of psoriasis treated with etanercept exhibited dramatic improvement in disease BSA. However, the patient developed thrombocytopenia (platelet count ¼ 88,000), which recurred during a subsequent course of treatment with etanercept. Discontinuation of treatment caused a relapse of psoriasis (BSA ¼ 20%). Subsequent treatment with one 12-week course of alefacept resulted in decrease in BSA to 5% within 10 weeks and had no adverse effects. Case 3: A 47-year-old white male with a 15-year history of psoriasis was treated with infliximab after failing previous etanercept and adalimumab treatments. Although the patient had no prior cardiac history, he was hospitalized with congestive heart failure and sepsis within 2 months of initiation of infliximab treatment. Two months later, the patient presented with a disease BSA of 70%. Ongoing treatment with alefacept resulted in decrease of BSA to 25% with no associated adverse cardiac events.
J AM ACAD DERMATOL
AB133
P2672
Efficacy of efalizumab for the treatment of moderate to severe plaque psoriasis: A prospective, 24-week, open-label phase IIIb/IV clinical trial in patients from Latin America Fernando M. Stengel, MD, Instituto Universitario Cemic, Buenos Aires, Argentina; Edgardo Chouela, MD, PhD, Hospital Cosme Argerich, Universidad de Buenos Aires, Buenos Aires, Argentina; Maria Denise Fonseca Takahashi, Faculdade de Medicina de USP (Hospital das Clinicas), Sao Paulo, Brazil; Mario Amaya, Hospital de Especialidadaes, IMSS, Monterrey NL, Mexico
Topical clobetasol propionate spray is effective for the treatment of patients with moderate to severe plaque psoriasis already on a stable, ongoing treatment regimen Steven Feldman, MD, PhD, Wake Forest University -School of Medicine, WinstonSalem, NC, United States
Objectives: Efalizumab, a recombinant humanized monoclonal IgG1 antibody against CD11a, inhibits key T-cell mediated processes central to psoriasis pathogenesis. Efalizumab is approved for the treatment of adults with moderate to severe chronic plaque psoriasis in more than 50 countries worldwide. This study analyzed the efficacy and safety of efalizumab in Latin American patients with moderate to severe plaque psoriasis. Efficacy results are reported here; safety results are presented separately. Methods: In this 24-week, open-label, single-arm phase IIIb/IV trial, adults ($18 yrs of age) with moderate to severe plaque psoriasis (body surface area $10%) who were candidates for systemic therapy received efalizumab subcutaneously once a week for 24 weeks (0.7 mg/kg conditioning dose and 1 mg/kg/wk thereafter). Efficacy was assessed via: (1) percentage of patients with Physician’s Global Assessment (PGA) of ‘‘excellent’’ (75-99% improvement) or ‘‘cleared’’ (100% improvement) at week 24; (2) percentage of patients with at least good disease control at week 24 defined by Psoriasis Area and Severity Index (PASI) \8 (or 50% reduction in PASI); Dermatology Life Quality Index (DLQI) \6; and no serious adverse events (SAEs), no treatment-related severe adverse events (AEs), or early study withdrawal; (3) assessment of PASI-75 ($75% reduction vs. baseline) and PASI50 ($50% reduction vs. baseline) response rates. Additional endpoints reported elsewhere included changes over time in PASI, Nail Psoriasis Severity Index, Palmoplantar Pustular Psoriasis Area and Severity Index, Psoriasis Scalp Severity Index, DLQI, and SF-36 Health Survey. Statistical analysis was performed on the intent-to-treat (ITT) population, using nonresponder imputation (NRI; missing ¼ nonresponders), and the last observation carried forward (LOCF) for missing data. Results: In total, 189 patients from 24 centers (Argentina, n ¼ 47; Brazil, n ¼ 81; Mexico, n ¼ 61) were included in the ITT population. Most patients (72.5%, 137/189) completed treatment. At week 24, 46.0% (NRI) and 48.7% (LOCF) of the ITT population achieved a PGA score of ‘‘excellent’’ or ‘‘cleared.’’ The percentage of patients achieving a PASI 75 or PASI 50 response at week 24 was 44.4% and 61.9%, respectively, with NRI.
Patients with psoriasis are often frustrated with their treatment. Patients may fail to clear with topical or even potent systemic agents. A phase IV, multicenter, openlabel trial of 4 weeks of twice daily clobetasol propionate 0.05% spray added on to stable existing systemic or topical therapies was conducted in 731 patients with moderate to severe plaque psoriasis (involving between 3% and 20% BSA). Systemic therapies must have been initiated at least 3 months before starting this study and topical therapies must have been initiated at least 1 month before starting this study. Primary efficacy outcomes included change in target plaque severity and investigator global assessment of improvement. Treatment success was defined as a rating of clear or almost clear or improvement by at least 2 points on the 6-point target plaque severity scale. Tolerability, adverse events and subject assessments were also included. Target plaque severity success was seen in 59% of patients at week 2 and 80% of patients at week 4. Furthermore, 41% were clear or almost clear at week 2 and 70% were clear or almost clear at week 4. At weeks 2 and 4, 27% and 62% of patients, respectively, were globally clear or almost clear. Pruritus and dryness were the most common side effects, reported in 6% and 5% of patients, respectively. A total of 74 adverse events were reported, of which 34 were determined to be possibly, probably, or definitely related to the study medication. Of these, 1 case of atrophy occurred and was considered to be probably related to treatment. The development of a non-messy clobetasol propionate spray preparation facilitates patients’ use of the medication. The product is highly and rapidly effective in patients with moderate to severe psoriasis even when they are already on an ongoing, stable treatment regimen. Study and poster support provided by Galderma Laboratories, L.P.
Conclusions: The efficacy results observed in Latin American patients with moderate to severe plaque psoriasis confirm those obtained in previous efalizumab clinical trials conducted in Europe and North America. 100% supported by Genentech, Inc.
P2671 Use of extended courses of alefacept in the treatment of moderate to severe psoriasis Aditya Gupta, MD, PhD, MBA, Mediprobe Research Inc., London, ON, Canada
P2673 Successful treatment of psoriasis with alefacept in patients with previous adverse reactions to anti-TNFa treatments: Three case studies Tiffani Hamilton, MD, Atlanta Dermatology, Vein & Research Center, Alpharetta, GA, United States
Introduction: Alefacept is an immunosuppressive dimeric fusion protein that interferes with T-lymphocyte activation. Results from phase II/III clinical trials indicate alefacept given in an FDA-approved 12-week dosing/12-week follow-up regimen provides a 75% reduction in psoriasis area and severity index (PASI) score (PASI 75) in 28% of subjects with moderate to severe plaque psoriasis. Extended use regimens of alefacept have shown that longer dosing regimens (up to 16 weeks) can increase the efficacy without compromising patient safety. Objectives: An open-label, single-center, extended-dosing study is being performed to investigate the safety and efficacy of continuous dosing with alefacept for up to 24 weeks for subjects with moderate to severe plaque psoriasis. Methods: All subjects with moderate to severe chronic plaque psoriasis receive an initial 12-week treatment course of alefacept 15 mg IM. Subjects failing to achieve a 90% decrease in PASI score (PASI 90) at week 12 continue to receive up to 12 additional weekly doses of alefacept with further evaluation at weeks 16, 20, and 24. Alefacept dosing will be discontinued in subjects achieving a PASI 90 score or higher at weeks 16 or 20. At the end of the treatment phase, subjects are followed for an additional 12 weeks. Results: To date, 30 subjects have completed the initial 12-week dosing of alefacept, of which 27 subjects have completed the consecutive 12-week dosing period. One subject achieved PASI 90 at week 16; PASI 90 was maintained to week 36 without further drug use in this subject. The mean percent reduction in PASI score from baseline increased with treatment duration from 27.3% at week 12, to 43.6% at week 16, and 55.2% at week 24. At week 24, 33.3% (9/27) achieved PASI-75 or higher. Of the 16 subjects who have completed the 12-week follow-up period, 43.8% (7/16) of subjects continued to improve from week 24 to week 36. One subject maintained a 64% reduction in PASI from week 24 to week 36 without further treatment. No safety issues have been noted with this extended-dosing regimen. Conclusions: This interim data suggests that continuous dosing with alefacept up to 24 weeks is safe and effective.
Conclusions: Alefacept is effective and safe in treating these 3 patients with psoriasis for whom prior treatments with anti-TNFa drugs were unsuccessful or complicated by adverse events. Thus alefacept could be considered for treating patients with psoriasis for whom anti-TNFa drugs are not an option.
Supported by Astellas Pharma Canada Inc.
Supported by Astellas Pharma US, Inc.
FEBRUARY 2008
Rationale and goal: Biologic drugs have been shown to be effective in treating psoriasis. However, treatment with anti-TNFa drugs can cause rebound effects on stoppage and may even induce psoriasis. The objective of these case studies was to evaluate the efficacy and safety of alefacept, a T-cell agent, in treating patients with psoriasis for whom anti-TNFa therapies were unsuccessful. Case 1: A 56-year-old female with a 15-year history of psoriasis and worsening disease after a 6-month course of etanercept was enrolled in a trial evaluating infliximab. However, she continued to worsen as the trial progressed with her disease body surface area (BSA) increasing to 50% (baseline BSA ¼ 12%) during the open label portion and thus was discontinued from the study. Subsequently, treatment with two 12-week courses of alefacept resulted in decrease in her disease BSA to 2%. Case 2: A 37-year-old black male with a 12-year history of psoriasis treated with etanercept exhibited dramatic improvement in disease BSA. However, the patient developed thrombocytopenia (platelet count ¼ 88,000), which recurred during a subsequent course of treatment with etanercept. Discontinuation of treatment caused a relapse of psoriasis (BSA ¼ 20%). Subsequent treatment with one 12-week course of alefacept resulted in decrease in BSA to 5% within 10 weeks and had no adverse effects. Case 3: A 47-year-old white male with a 15-year history of psoriasis was treated with infliximab after failing previous etanercept and adalimumab treatments. Although the patient had no prior cardiac history, he was hospitalized with congestive heart failure and sepsis within 2 months of initiation of infliximab treatment. Two months later, the patient presented with a disease BSA of 70%. Ongoing treatment with alefacept resulted in decrease of BSA to 25% with no associated adverse cardiac events.
J AM ACAD DERMATOL
AB133