Jeffrey M Weinberg1. 1. Department of Dermatology, St. Luke's-Roosevelt Hospital Center, 1090 Amsterdam Avenue, Suite 11D, New York, NY 10025, USA. jmw27@columbia.edu
Abstract
BACKGROUND: Psoriasis is a chronic skin disorder that affects approximately 2% of the US and European populations. One of the major focuses in psoriasis research has been the development of biologic therapies that provide selective, immunologically directed intervention with fewer adverse effects than traditional therapies. OBJECTIVE: The aim of this review was to summarize the progress of 4 biologic agents available or under investigation for clinical use: infliximab, etanercept, efalizumab, and alefacept. METHODS: Relevant information was identified through a MEDLINE search of the literature (1966 to May 2003) using the terms biologic therapy, psoriasis, infliximab, etanercept, efalizumab, and alefacept. In addition, meeting posters from the American Academy of Dermatology (2003) and International Investigative Dermatology (2003) were reviewed and included if perceived to be reliable and relevant. RESULTS: In a Phase II trial of infliximab, the percentages of patients reaching > or =75% improvement from baseline in the psoriasis area and severity index (PASI 75) at week 10 were as follows: 6% with placebo (3/51), 72% with infliximab 3 mg/kg (71/98), and 88% with infliximab 5 mg/kg (87/99). In a Phase III study, 34% of patients receiving etanercept 25 mg SC twice weekly (55/162) achieved PASI 75 at 12 weeks and 44% (71/162) at 24 weeks. Also, 49% of those receiving etanercept 50 mg (81/164) achieved PASI 75 at 12 weeks, and 59% (97/164) at 24 weeks. In 2 Phase III trials with SC efalizumab 1.0 mg/kg or 2.0 mg/kg or placebo, 30% in the 1.0-mg/kg per week group (117/394) achieved PASI 75; in the 2.0-mg/kg per week group, 28% (113/409) did. In the placebo, 3.4% (10/292) achieved PASI 75. In a Phase III trial of IM alefacept 15 mg once weekly for 12 weeks, IM alefacept 10 mg once weekly for 12 weeks, or placebo, 21% of the 15-mg dose group (35/166) achieved PASI 75 at 2 weeks after the last dose, compared with 5% of the placebo group (8/168). In a Phase III study of the efficacy and tolerability of once-weekly alefacept 7.5 mg via IV bolus, 14% (53/367) and 4% (7/186) of patients receiving alefacept and placebo achieved PASI 75 at week 14, respectively. Among those who received 2 courses of alefacept, 40% (73/183) and 71% (130/183) achieved PASI 75 and > or = 50% improvement in PASI, respectively. All 4 drugs have been generally well tolerated. CONCLUSIONS: In the patients treated to date, infliximab, etanercept, efalizumab, and alefacept have achieved successful therapy of psoriasis without the organ toxicity seen with traditional systemic therapies. Potential limitations in the use of these agents include the expected high costs of treatment, lack of long-term follow-up, and the selective nature of the patient populations treated thus far.
BACKGROUND:Psoriasis is a chronic skin disorder that affects approximately 2% of the US and European populations. One of the major focuses in psoriasis research has been the development of biologic therapies that provide selective, immunologically directed intervention with fewer adverse effects than traditional therapies. OBJECTIVE: The aim of this review was to summarize the progress of 4 biologic agents available or under investigation for clinical use: infliximab, etanercept, efalizumab, and alefacept. METHODS: Relevant information was identified through a MEDLINE search of the literature (1966 to May 2003) using the terms biologic therapy, psoriasis, infliximab, etanercept, efalizumab, and alefacept. In addition, meeting posters from the American Academy of Dermatology (2003) and International Investigative Dermatology (2003) were reviewed and included if perceived to be reliable and relevant. RESULTS: In a Phase II trial of infliximab, the percentages of patients reaching > or =75% improvement from baseline in the psoriasis area and severity index (PASI 75) at week 10 were as follows: 6% with placebo (3/51), 72% with infliximab 3 mg/kg (71/98), and 88% with infliximab 5 mg/kg (87/99). In a Phase III study, 34% of patients receiving etanercept 25 mg SC twice weekly (55/162) achieved PASI 75 at 12 weeks and 44% (71/162) at 24 weeks. Also, 49% of those receiving etanercept 50 mg (81/164) achieved PASI 75 at 12 weeks, and 59% (97/164) at 24 weeks. In 2 Phase III trials with SC efalizumab 1.0 mg/kg or 2.0 mg/kg or placebo, 30% in the 1.0-mg/kg per week group (117/394) achieved PASI 75; in the 2.0-mg/kg per week group, 28% (113/409) did. In the placebo, 3.4% (10/292) achieved PASI 75. In a Phase III trial of IM alefacept 15 mg once weekly for 12 weeks, IM alefacept 10 mg once weekly for 12 weeks, or placebo, 21% of the 15-mg dose group (35/166) achieved PASI 75 at 2 weeks after the last dose, compared with 5% of the placebo group (8/168). In a Phase III study of the efficacy and tolerability of once-weekly alefacept 7.5 mg via IV bolus, 14% (53/367) and 4% (7/186) of patients receiving alefacept and placebo achieved PASI 75 at week 14, respectively. Among those who received 2 courses of alefacept, 40% (73/183) and 71% (130/183) achieved PASI 75 and > or = 50% improvement in PASI, respectively. All 4 drugs have been generally well tolerated. CONCLUSIONS: In the patients treated to date, infliximab, etanercept, efalizumab, and alefacept have achieved successful therapy of psoriasis without the organ toxicity seen with traditional systemic therapies. Potential limitations in the use of these agents include the expected high costs of treatment, lack of long-term follow-up, and the selective nature of the patient populations treated thus far.