BACKGROUND: Alefacept, a fully human LFA-3/IgG(1) fusion protein, is a selective biological agent approved in the United States for the treatment of chronic plaque psoriasis. In phase 3 trials, clinical improvement and prolonged off-treatment remission of psoriasis correlated with reductions in circulating memory T cells. Reductions in pathogenic epidermal T cells in psoriatic lesions also have been noted following phototherapy with ultraviolet B (UVB) light. Because alefacept and UVB target T cells in different ways, combination therapy with these two agents may lead to greater efficacy. OBJECTIVES: To determine the safety, tolerability, and efficacy trends of combination therapy with alefacept plus UVB light in patients with chronic plaque psoriasis. METHODS: In an open-label, parallel-group study conducted at two sites, one in France and one in the United States, patients with chronic plaque psoriasis who were candidates forphototherapy received 12-weekly intramuscular injections of alefacept, 15 mg. In addition, patients were randomized to one of three treatment arms: no UVB treatment, 6-week UVB treatment, and 12-week UVB treatment. UVB treatment consisted of narrowband (NB) UVB at the site in France and broadband (BB) UVB at the site in the United States. The 12-week treatment period was followed by a 12-week follow-up period. Clinic visits occurred weekly during treatment and every 2-4 weeks during follow-up. RESULTS: A total of 60 patients (n = 30/site) were enrolled in the study. Alefacept was well tolerated when administered in combination with UVB treatment and as monotherapy. There was no evidence of increased phototoxicity or photosensitivity with the combination. At each study site, alefacept/UVB provided a higher overall response rate and led to a more rapid onset of response compared with alefacept monotherapy. Of patients who achieved > or = 50% reduction from baseline Psoriasis Area Severity Index (PASI 50) at 2 weeks after the last dose of alefacept, 75-100% in the combination therapy groups maintained this response throughout follow-up in the absence of further psoriasis therapy. CONCLUSIONS: In patients with chronic plaque psoriasis, combination therapy with alefacept plus short-term (6-12 weeks) UVB treatment is well tolerated with a trend toward greater and more rapid efficacy than alefacept alone.
RCT Entities:
BACKGROUND: Alefacept, a fully human LFA-3/IgG(1) fusion protein, is a selective biological agent approved in the United States for the treatment of chronic plaque psoriasis. In phase 3 trials, clinical improvement and prolonged off-treatment remission of psoriasis correlated with reductions in circulating memory T cells. Reductions in pathogenic epidermal T cells in psoriatic lesions also have been noted following phototherapy with ultraviolet B (UVB) light. Because alefacept and UVB target T cells in different ways, combination therapy with these two agents may lead to greater efficacy. OBJECTIVES: To determine the safety, tolerability, and efficacy trends of combination therapy with alefacept plus UVB light in patients with chronic plaque psoriasis. METHODS: In an open-label, parallel-group study conducted at two sites, one in France and one in the United States, patients with chronic plaque psoriasis who were candidates for phototherapy received 12-weekly intramuscular injections of alefacept, 15 mg. In addition, patients were randomized to one of three treatment arms: no UVB treatment, 6-week UVB treatment, and 12-week UVB treatment. UVB treatment consisted of narrowband (NB) UVB at the site in France and broadband (BB) UVB at the site in the United States. The 12-week treatment period was followed by a 12-week follow-up period. Clinic visits occurred weekly during treatment and every 2-4 weeks during follow-up. RESULTS: A total of 60 patients (n = 30/site) were enrolled in the study. Alefacept was well tolerated when administered in combination with UVB treatment and as monotherapy. There was no evidence of increased phototoxicity or photosensitivity with the combination. At each study site, alefacept/UVB provided a higher overall response rate and led to a more rapid onset of response compared with alefacept monotherapy. Of patients who achieved > or = 50% reduction from baseline Psoriasis Area Severity Index (PASI 50) at 2 weeks after the last dose of alefacept, 75-100% in the combination therapy groups maintained this response throughout follow-up in the absence of further psoriasis therapy. CONCLUSIONS: In patients with chronic plaque psoriasis, combination therapy with alefacept plus short-term (6-12 weeks) UVB treatment is well tolerated with a trend toward greater and more rapid efficacy than alefacept alone.