Background: The US National Psoriasis Foundation recently recommended that PASI 50 and PASI 75 response rates be used in clinical trials to enable comparisons across studies of different psoriasis therapies. To date, ...Background: The US National Psoriasis Foundation recently recommended that PASI 50 and PASI 75 response rates be used in clinical trials to enable comparisons across studies of different psoriasis therapies. To date, these response rates have not been reported for the two-compound ointment containing calcipotriol and betamethasone dipropionate (Daivobet/Dovobet; LEO Pharma, Ballerup, Denmark). Further, in order to compare Daivobetwith other therapeutics recently presented to the European regulatory authorities and the FDA, comparison with the biologicals, efalizumab, etanercept and alefacept, were also made. Objectives: To present the PASI 50 and PASI 75 results for the two-compound ointment containing calcipotriol and betamethasone dipropionate. Methods: Data from six phase III studies conducted with the two-compound ointment were pooled and the PASI 50 and PASI 75 response rates calculated for patients with severe (PASI≥17) or less severe disease (PASI < 17) at treatment commencement. Results for the biological therapies, efalizumab, etanercept and alefacept, were obtained from relevant published phase III studies. Results: PASI 50 and PASI 75 were achieved by more patients treated with the two-compound ointment than with the individual components. In patients with severe disease, the PASI 50 response rate after 4 weeks’treatment was 88.8%with the two-compound ointment, 69.2%with betamethasone dipropionate, 53.8%with calcipotriol, and 30.0%with ointment vehicle. In comparison, 12 weeks’treatment with the biologicals resulted in PASI 50 response rates of 59%with efalizumab, 74%with etanercept, and 56%with alefacept. Conclusions: The two-compound ointment is effective, producing a PASI 50 and PASI 75 response in greater than 80%and 50%of patients, respectively, regardless of psoriasis severity.展开更多
Background: Interleukin (IL)- 20 and IL- 19 are recently discovered members of the IL- 10 family of cytokines. The skin of transgenic mice overexpressing IL- 20 shows histological changes resembling some of those seen...Background: Interleukin (IL)- 20 and IL- 19 are recently discovered members of the IL- 10 family of cytokines. The skin of transgenic mice overexpressing IL- 20 shows histological changes resembling some of those seen in psoriasis, i.e. thickened epidermis, hyperkeratosis and a compact stratumcorneum. IL- 19 and IL- 20, as well as their receptor complexes, IL- 20Rα /IL- 20Rβ and IL- 22Rα /IL- 20Rβ , are expressed in human skin. Objectives: To study the dynamics of IL- 19 and IL- 20 gene expression as well as the expression of their receptor subunits in psoriatic skin lesions. Methods: Punch biopsies from patients with plaque- type psoriasis were collected before, during and after 28 days of treatment with either calcipotriol or ciclosporin (CsA). IL- 20, IL- 19, IL- 20Rα , IL- 20Rβ and IL- 22Rα mRNA expression were determined by quantitative reverse transcriptase- polymerase chain reaction. Results: We found IL- 19 and IL- 20 mRNA expression in lesional psoriatic skin to be strongly upregulated comparedwith nonlesional psoriatic skin by a factor of 65 and 22, respectively. In contrast to previous reports, IL- 20Rα and IL- 20Rβ mRNA levels showed a modest but statistically significant decrease in lesional psoriatic skin compared with nonlesional psoriatic skin. During treatment with calcipotriol or CsA, IL- 19 and IL- 20 mRNA levels decrease in accordance with the clinical improvement of psoriasis. Neither IL- 19, IL- 20, nor receptor subunit mRNA expression in lesional psoriatic skin reaches the levels of nonlesional skin during this short- term treatment. These findings are in line with the residual disease activity observed at the end of treatment. Conclusions: The increased IL- 19 and IL- 20 mRNA expression levels in lesional psoriatic skin suggest that these two cytokines play a role in the pathogenesis of psoriasis. An imbalance in the receptor complexes for IL- 19 and IL- 20 might contribute to their suspected pathogenic effects.展开更多
文摘Background: The US National Psoriasis Foundation recently recommended that PASI 50 and PASI 75 response rates be used in clinical trials to enable comparisons across studies of different psoriasis therapies. To date, these response rates have not been reported for the two-compound ointment containing calcipotriol and betamethasone dipropionate (Daivobet/Dovobet; LEO Pharma, Ballerup, Denmark). Further, in order to compare Daivobetwith other therapeutics recently presented to the European regulatory authorities and the FDA, comparison with the biologicals, efalizumab, etanercept and alefacept, were also made. Objectives: To present the PASI 50 and PASI 75 results for the two-compound ointment containing calcipotriol and betamethasone dipropionate. Methods: Data from six phase III studies conducted with the two-compound ointment were pooled and the PASI 50 and PASI 75 response rates calculated for patients with severe (PASI≥17) or less severe disease (PASI < 17) at treatment commencement. Results for the biological therapies, efalizumab, etanercept and alefacept, were obtained from relevant published phase III studies. Results: PASI 50 and PASI 75 were achieved by more patients treated with the two-compound ointment than with the individual components. In patients with severe disease, the PASI 50 response rate after 4 weeks’treatment was 88.8%with the two-compound ointment, 69.2%with betamethasone dipropionate, 53.8%with calcipotriol, and 30.0%with ointment vehicle. In comparison, 12 weeks’treatment with the biologicals resulted in PASI 50 response rates of 59%with efalizumab, 74%with etanercept, and 56%with alefacept. Conclusions: The two-compound ointment is effective, producing a PASI 50 and PASI 75 response in greater than 80%and 50%of patients, respectively, regardless of psoriasis severity.
文摘Background: Interleukin (IL)- 20 and IL- 19 are recently discovered members of the IL- 10 family of cytokines. The skin of transgenic mice overexpressing IL- 20 shows histological changes resembling some of those seen in psoriasis, i.e. thickened epidermis, hyperkeratosis and a compact stratumcorneum. IL- 19 and IL- 20, as well as their receptor complexes, IL- 20Rα /IL- 20Rβ and IL- 22Rα /IL- 20Rβ , are expressed in human skin. Objectives: To study the dynamics of IL- 19 and IL- 20 gene expression as well as the expression of their receptor subunits in psoriatic skin lesions. Methods: Punch biopsies from patients with plaque- type psoriasis were collected before, during and after 28 days of treatment with either calcipotriol or ciclosporin (CsA). IL- 20, IL- 19, IL- 20Rα , IL- 20Rβ and IL- 22Rα mRNA expression were determined by quantitative reverse transcriptase- polymerase chain reaction. Results: We found IL- 19 and IL- 20 mRNA expression in lesional psoriatic skin to be strongly upregulated comparedwith nonlesional psoriatic skin by a factor of 65 and 22, respectively. In contrast to previous reports, IL- 20Rα and IL- 20Rβ mRNA levels showed a modest but statistically significant decrease in lesional psoriatic skin compared with nonlesional psoriatic skin. During treatment with calcipotriol or CsA, IL- 19 and IL- 20 mRNA levels decrease in accordance with the clinical improvement of psoriasis. Neither IL- 19, IL- 20, nor receptor subunit mRNA expression in lesional psoriatic skin reaches the levels of nonlesional skin during this short- term treatment. These findings are in line with the residual disease activity observed at the end of treatment. Conclusions: The increased IL- 19 and IL- 20 mRNA expression levels in lesional psoriatic skin suggest that these two cytokines play a role in the pathogenesis of psoriasis. An imbalance in the receptor complexes for IL- 19 and IL- 20 might contribute to their suspected pathogenic effects.
