- Email: [email protected]
Efficacy of infliximab in patients with severe psoriasis: Subgroup analysis from clinical trials
P2619
P2701
Effect of a new cosmetic formulation on reducing cutaneous pigmentation: A clinical and biometrological approach Jean Luc Levy, Centre Laser Dermatologique, Marseille, France; Lise Agopian Simoneau, Biophyderm, Montpellier, France; Bernard Chadoutaud, Clinreal Online, Toulouse, France; Philippe Msika, Laboratoires ExpanScience, Epernon, France Introduction: Intracellular signal transduction pathways regulating melanogenesis imply PKC, cAMP through the activation of PKA and NO. A new whitening formulation, that targets these three different pathways, has been tested on melasma with image analysis and a particular interest on the quality of life (QoL) of the volunteers.
Value of isolated populations in probing for genes in psoriatic arthritis and psoriasis Wayne Gulliver, MD, NewLab Clinical Research Inc., St. John’s, NF, Canada; Dafna Galdman, MD, University of Toronto, Toronto, ON, Canada; Proton Raham, MD, Memorial University of Newfoundland, St. John’s, NF, Canada
Methods and Materials: The tested product was a cosmetic cream containing PKC and PKA inhibitors, and vitamins E and C. It has been applied 2 x/day for 4 months on 20 volunteers with epidermic melasma and phototype IV or V. MASI (melasma area and severity index), melanic index (MI), (mexameter MX 16), and QoL (MELASQOL) were evaluated at D0, D60 and D120. Cutaneous dyschromy was analyzed by image analysis of UV photography. Results: With the new formulation, we observed a significant decrease of MASI of 36.1% (D60) and 51.3% (D120) compared to D0, and between D60 and D120 ( 23.7%, p = 0.0022). The MI is not modified on normal skin, while it is statistically decreased on hyperpigmented areas (maximum at D60). QoL was also statistically improved by the tested product: 16.6%, especially for discomfort feeling ( 23.4%), disappointment ( 21%), and embarrassment ( 22%). Image analysis illustrated these significant improvements. Conclusion: A novel cosmetic formulation containing PKC and PKA inhibitor 1 vitamins E and C inhibits melanogenesis. Clinical and biometrological measurements attested its statistically significant whitening effects on melasma. A specific impact has been shown on QoL of the patients. Images analysis of photography taken under UV light confirm the clinical observations. 100% is supported by Laboratoires EXPANSCIENCE.
The genetic contribution of PsA and psoriasis is evidenced by population-based and twin studies, as well as molecular investigations from candidate gene and linkage analysis. Despite extensive ongoing research, few candidate genes have been identified and validated in PsA and psoriasis. Young founder populations, like the Newfoundland population, is now the focus of intensive interest for gene identification in complex diseases. Although the utility of such populations for this purpose remains unproven, it is widely assumed that homogenous populations offer advantages in gene identification. The benefits in pursing gene identification studies in such populations include an increase in allele and locus homogeneity. This is of importance given the etiologic heterogeneity that characterizes complex diseases like PsA and psoriasis. We have used a similar standardized clinical protocol, identical molecular markers, and one genetic laboratory to study two White Canadian populations of north European ancestry (a founder population from Newfoundland and an admixed outbred population from Toronto) to investigate the genetics of PsA. Candidate genes studied to date include HLA-Cw0602 SEEK1, CARD15, IL-1 (alpha, beta, RA), TNF-alpha promoter polymorphisms, CDSN, SLC22A4, SLC22A5, SLC9A3R1 and RUNX1, NFkB, tp53, and PTPN22. In the study of psoriasis related genes in the Newfoundland and Labrador population genomewide scanning with 199 sib pairs was employed to investigate potential candidate genes. Associations with SEEK1, CARD15, TNF-alpha, and IL-1-alpha have been noted in the Newfoundland population in PsA, which have not been replicated in the Toronto population. In the Newfoundland psoriasis population, significant associations with TNF-alpha and HLA-Cw6 were found. Similar associations have been noted in other populations including TNF-alpha, with a German psoriatic population and HLA Cw6 and in Icelandic populations. The lack of replication of initial associations may be a result of false positive reportings (due to extended LD, multiple testing and population stratification), false negative findings (due to small effect size coupled with inadequate sample size of validation studies), and population specific differences. We will illustrate some of these issues with the data generated from our studies. Commercial support: None identified.
PSORIASIS AND OTHER PAPULOSQUAMOUS DISORDERS P2700 Influence of etanercept on serum liver related tests and viral load values in patients with psoriasis and hepatitis C infection Maria Esposito, MD, Department of Dermatology, University of Rome Tor Vergata, Rome, Italy; Luca Bianchi, MD, Department of Dermatology, University of Rome Tor Vergata, Rome, Italy; Annamaria Mazzotta, MD, Department of Dermatology, University of Rome Tor Vergata, Rome, IA, Italy; Sergio Chimenti, MD, Department of Dermatology, University of Rome Tor Vergata, Rome, Italy Background: Hepatitis C virus (HCV) infection is the most common blood-borne infectious diseases worldwide. In patients with psoriasis and concomitant hepatitis, immunosuppressive agents for psoriasis may be associated with an increased risk of reactivation or worsening of HCV infection. Although the role of tumor necrosis factor-alpha (TNF-a) in hepatitis in not fully understood, elevated TNF-a levels have been documented in patients with hepatitis C and are associated with a worse prognosis. Etanercept is a fully human TNF-a receptor that modulates biologic responses induced by TNF-a. Accumulated data suggest that etanercept, may be a therapeutic option in patients with hepatitis C and coexisting immunological disorders. Our objective was to examine the influence of treatment with etanercept on serum liver related tests (LRTs) and viral load values in patients with psoriasis and concomitant hepatitis C infection.
P2702 Efficacy of infliximab in patients with severe psoriasis: Subgroup analysis from clinical trials A. Menter, MD, Baylor University Medical Center, Dallas, TX, United States; C. Guzzo, MD, Centocor Research and Development, Inc., Malvern, PA, United States; S. Li, PhD, Centocor Research and Development, Inc., Malvern, PA, United States; A.B. Gottlieb, Tufts-New England Medical Center, Boston, MA, United States Objective: To evaluate IFX efficacy in patients with more severe psoriasis. Methods: Data for the integrated efficacy analysis was obtained from randomized, PBO controlled trials in moderate-to-severe psoriasis patients (EXPRESS, EXPRESS II SPIRIT). IFX doses 3 to 5 mg/kg induction followed by scheduled or ‘‘as needed’’ (PRN) maintenance (EXPRESS, EXPRESS II only). Severe psoriasis was defined as either 1) baseline BSA [ = 20% or 2) baseline BSA [ = 20% and PASI [ = 20. The common primary endpoint was the proportion of patients achieving [ = 75% improvement in PASI from baseline (PASI-75) at wk 10. The efficacy of IFX in patients by previous use of phototherapy (UVB, PUVA) or [ = 1 systemic therapy (MTX, acitretin, cyclosporine) as well as response to these medications was analyzed.
Conclusions: In our study we observed that viral load measurements improved and LRBs showed a marked reduction during the treatment with etanercept. Despite larger studies needed, etanercept may be an effective and safe option for psoriasis and psoriatic arthritis in patients with concomitant HCV infection.
Results: Of 1,462 patients randomized, 991 (68%) were severe, a BSA [ = 20%. The most frequent treatment received by history was UVB (56%) followed by MTX (43.5%), PUVA (39.9%), acitretin (23.6%), and cyclosporine (22.1%). Phototherapy (UVB or PUVA) was used by 72.7% of patients and was similar to the number of patients who received any systemic treatments (PUVA, MTX, acitretin, or cyclosporine, 69.3%). The number of patients defined as severe with BSA [ = 20% and a PASI [ = 20 was 592; the distribution of prior psoriasis therapy was similar to patients with a BSA [ = 20%. At week 10, among patients with BSA [ = 20% at baseline, more IFX-treated patients achieved PASI-75 in the subgroups of patients who received phototherapy (79.4% versus 2.5%, combined IFX vs PBO, respectively) and who received systemics (76.0% versus 1.2%, combined IFX vs PBO, respectively) (p \ 0.001, for both). PASI-75 response was similar among patients with a BSA [ = 20% and a PASI [ = 20 (phototherapy: 81.8% versus 2.1% and systemics: 78.6% versus 1.0%, for combined IFX and PBO, respectively [p \ 0.001, for both]). Patients with BSA [ = 20% had a similar PASI-75 response to IFX whether they were dissatisfied with or were intolerant to either prior phototherapy (73.3% versus 1.9%, combined IFX versus PBO) or [ = 1 systemic therapy (68.6% versus 0.0%, combined IFX versus PBO) (p \ 0.001, respectively). In all studies through week 16, the number of patients with a BSA [ = 20% with [= 1 SAE among IFX- and PBO-treated patients was comparable in both subgroups (phototherapy: 3.2% versus 2.5%; systemics: 3.6% versus 2.5%, for combined IFX and PBO, respectively). Conclusions: IFX is effective is treating patients with more severe psoriasis, the majority of which had been previously treated with either phototherapy or systemic therapy.
Commercial support: None identified.
This study was sponsored by Centocor, Inc.
Methods: Eight (8) patients (5 men, 3 women), affected by plaque-type psoriasis (3) and psoriatic arthritis (5) unresponsive to conventional treatments, presented with serologic evidence of HCV infection. They were selected to receive etanercept 50 mg subcutaneously administered twice weekly for 12 weeks followed by 25 mg for 12 weeks. Values for HCV viral load and LRTs were evaluated at baseline and after 24 weeks of treatment, as well as safety and efficacy that was assessed by psoriasis area and severity index (PASI) and Ritchie index (RI) in patients with arthritis. Results: Mean baseline PASI decreased from 12.8 (range, 11-17.6, SD: 3.4) to 2.9 (range, 0-5.8, SD: 1.02) at week-24. Mean baseline RI showed a reduction from 66 (range, 40-80, SD: 15.1) to 29 (range, 10-95, SD: 37.1). Among all patients, mean value of the LRTs substantially decreased during the treatment period. Values for HCV viral load showed slight reduction, although not statistically significant (p \ 0.01).
AB174
J AM ACAD DERMATOL
FEBRUARY 2007
P2701
Effect of a new cosmetic formulation on reducing cutaneous pigmentation: A clinical and biometrological approach Jean Luc Levy, Centre Laser Dermatologique, Marseille, France; Lise Agopian Simoneau, Biophyderm, Montpellier, France; Bernard Chadoutaud, Clinreal Online, Toulouse, France; Philippe Msika, Laboratoires ExpanScience, Epernon, France Introduction: Intracellular signal transduction pathways regulating melanogenesis imply PKC, cAMP through the activation of PKA and NO. A new whitening formulation, that targets these three different pathways, has been tested on melasma with image analysis and a particular interest on the quality of life (QoL) of the volunteers.
Value of isolated populations in probing for genes in psoriatic arthritis and psoriasis Wayne Gulliver, MD, NewLab Clinical Research Inc., St. John’s, NF, Canada; Dafna Galdman, MD, University of Toronto, Toronto, ON, Canada; Proton Raham, MD, Memorial University of Newfoundland, St. John’s, NF, Canada
Methods and Materials: The tested product was a cosmetic cream containing PKC and PKA inhibitors, and vitamins E and C. It has been applied 2 x/day for 4 months on 20 volunteers with epidermic melasma and phototype IV or V. MASI (melasma area and severity index), melanic index (MI), (mexameter MX 16), and QoL (MELASQOL) were evaluated at D0, D60 and D120. Cutaneous dyschromy was analyzed by image analysis of UV photography. Results: With the new formulation, we observed a significant decrease of MASI of 36.1% (D60) and 51.3% (D120) compared to D0, and between D60 and D120 ( 23.7%, p = 0.0022). The MI is not modified on normal skin, while it is statistically decreased on hyperpigmented areas (maximum at D60). QoL was also statistically improved by the tested product: 16.6%, especially for discomfort feeling ( 23.4%), disappointment ( 21%), and embarrassment ( 22%). Image analysis illustrated these significant improvements. Conclusion: A novel cosmetic formulation containing PKC and PKA inhibitor 1 vitamins E and C inhibits melanogenesis. Clinical and biometrological measurements attested its statistically significant whitening effects on melasma. A specific impact has been shown on QoL of the patients. Images analysis of photography taken under UV light confirm the clinical observations. 100% is supported by Laboratoires EXPANSCIENCE.
The genetic contribution of PsA and psoriasis is evidenced by population-based and twin studies, as well as molecular investigations from candidate gene and linkage analysis. Despite extensive ongoing research, few candidate genes have been identified and validated in PsA and psoriasis. Young founder populations, like the Newfoundland population, is now the focus of intensive interest for gene identification in complex diseases. Although the utility of such populations for this purpose remains unproven, it is widely assumed that homogenous populations offer advantages in gene identification. The benefits in pursing gene identification studies in such populations include an increase in allele and locus homogeneity. This is of importance given the etiologic heterogeneity that characterizes complex diseases like PsA and psoriasis. We have used a similar standardized clinical protocol, identical molecular markers, and one genetic laboratory to study two White Canadian populations of north European ancestry (a founder population from Newfoundland and an admixed outbred population from Toronto) to investigate the genetics of PsA. Candidate genes studied to date include HLA-Cw0602 SEEK1, CARD15, IL-1 (alpha, beta, RA), TNF-alpha promoter polymorphisms, CDSN, SLC22A4, SLC22A5, SLC9A3R1 and RUNX1, NFkB, tp53, and PTPN22. In the study of psoriasis related genes in the Newfoundland and Labrador population genomewide scanning with 199 sib pairs was employed to investigate potential candidate genes. Associations with SEEK1, CARD15, TNF-alpha, and IL-1-alpha have been noted in the Newfoundland population in PsA, which have not been replicated in the Toronto population. In the Newfoundland psoriasis population, significant associations with TNF-alpha and HLA-Cw6 were found. Similar associations have been noted in other populations including TNF-alpha, with a German psoriatic population and HLA Cw6 and in Icelandic populations. The lack of replication of initial associations may be a result of false positive reportings (due to extended LD, multiple testing and population stratification), false negative findings (due to small effect size coupled with inadequate sample size of validation studies), and population specific differences. We will illustrate some of these issues with the data generated from our studies. Commercial support: None identified.
PSORIASIS AND OTHER PAPULOSQUAMOUS DISORDERS P2700 Influence of etanercept on serum liver related tests and viral load values in patients with psoriasis and hepatitis C infection Maria Esposito, MD, Department of Dermatology, University of Rome Tor Vergata, Rome, Italy; Luca Bianchi, MD, Department of Dermatology, University of Rome Tor Vergata, Rome, Italy; Annamaria Mazzotta, MD, Department of Dermatology, University of Rome Tor Vergata, Rome, IA, Italy; Sergio Chimenti, MD, Department of Dermatology, University of Rome Tor Vergata, Rome, Italy Background: Hepatitis C virus (HCV) infection is the most common blood-borne infectious diseases worldwide. In patients with psoriasis and concomitant hepatitis, immunosuppressive agents for psoriasis may be associated with an increased risk of reactivation or worsening of HCV infection. Although the role of tumor necrosis factor-alpha (TNF-a) in hepatitis in not fully understood, elevated TNF-a levels have been documented in patients with hepatitis C and are associated with a worse prognosis. Etanercept is a fully human TNF-a receptor that modulates biologic responses induced by TNF-a. Accumulated data suggest that etanercept, may be a therapeutic option in patients with hepatitis C and coexisting immunological disorders. Our objective was to examine the influence of treatment with etanercept on serum liver related tests (LRTs) and viral load values in patients with psoriasis and concomitant hepatitis C infection.
P2702 Efficacy of infliximab in patients with severe psoriasis: Subgroup analysis from clinical trials A. Menter, MD, Baylor University Medical Center, Dallas, TX, United States; C. Guzzo, MD, Centocor Research and Development, Inc., Malvern, PA, United States; S. Li, PhD, Centocor Research and Development, Inc., Malvern, PA, United States; A.B. Gottlieb, Tufts-New England Medical Center, Boston, MA, United States Objective: To evaluate IFX efficacy in patients with more severe psoriasis. Methods: Data for the integrated efficacy analysis was obtained from randomized, PBO controlled trials in moderate-to-severe psoriasis patients (EXPRESS, EXPRESS II SPIRIT). IFX doses 3 to 5 mg/kg induction followed by scheduled or ‘‘as needed’’ (PRN) maintenance (EXPRESS, EXPRESS II only). Severe psoriasis was defined as either 1) baseline BSA [ = 20% or 2) baseline BSA [ = 20% and PASI [ = 20. The common primary endpoint was the proportion of patients achieving [ = 75% improvement in PASI from baseline (PASI-75) at wk 10. The efficacy of IFX in patients by previous use of phototherapy (UVB, PUVA) or [ = 1 systemic therapy (MTX, acitretin, cyclosporine) as well as response to these medications was analyzed.
Conclusions: In our study we observed that viral load measurements improved and LRBs showed a marked reduction during the treatment with etanercept. Despite larger studies needed, etanercept may be an effective and safe option for psoriasis and psoriatic arthritis in patients with concomitant HCV infection.
Results: Of 1,462 patients randomized, 991 (68%) were severe, a BSA [ = 20%. The most frequent treatment received by history was UVB (56%) followed by MTX (43.5%), PUVA (39.9%), acitretin (23.6%), and cyclosporine (22.1%). Phototherapy (UVB or PUVA) was used by 72.7% of patients and was similar to the number of patients who received any systemic treatments (PUVA, MTX, acitretin, or cyclosporine, 69.3%). The number of patients defined as severe with BSA [ = 20% and a PASI [ = 20 was 592; the distribution of prior psoriasis therapy was similar to patients with a BSA [ = 20%. At week 10, among patients with BSA [ = 20% at baseline, more IFX-treated patients achieved PASI-75 in the subgroups of patients who received phototherapy (79.4% versus 2.5%, combined IFX vs PBO, respectively) and who received systemics (76.0% versus 1.2%, combined IFX vs PBO, respectively) (p \ 0.001, for both). PASI-75 response was similar among patients with a BSA [ = 20% and a PASI [ = 20 (phototherapy: 81.8% versus 2.1% and systemics: 78.6% versus 1.0%, for combined IFX and PBO, respectively [p \ 0.001, for both]). Patients with BSA [ = 20% had a similar PASI-75 response to IFX whether they were dissatisfied with or were intolerant to either prior phototherapy (73.3% versus 1.9%, combined IFX versus PBO) or [ = 1 systemic therapy (68.6% versus 0.0%, combined IFX versus PBO) (p \ 0.001, respectively). In all studies through week 16, the number of patients with a BSA [ = 20% with [= 1 SAE among IFX- and PBO-treated patients was comparable in both subgroups (phototherapy: 3.2% versus 2.5%; systemics: 3.6% versus 2.5%, for combined IFX and PBO, respectively). Conclusions: IFX is effective is treating patients with more severe psoriasis, the majority of which had been previously treated with either phototherapy or systemic therapy.
Commercial support: None identified.
This study was sponsored by Centocor, Inc.
Methods: Eight (8) patients (5 men, 3 women), affected by plaque-type psoriasis (3) and psoriatic arthritis (5) unresponsive to conventional treatments, presented with serologic evidence of HCV infection. They were selected to receive etanercept 50 mg subcutaneously administered twice weekly for 12 weeks followed by 25 mg for 12 weeks. Values for HCV viral load and LRTs were evaluated at baseline and after 24 weeks of treatment, as well as safety and efficacy that was assessed by psoriasis area and severity index (PASI) and Ritchie index (RI) in patients with arthritis. Results: Mean baseline PASI decreased from 12.8 (range, 11-17.6, SD: 3.4) to 2.9 (range, 0-5.8, SD: 1.02) at week-24. Mean baseline RI showed a reduction from 66 (range, 40-80, SD: 15.1) to 29 (range, 10-95, SD: 37.1). Among all patients, mean value of the LRTs substantially decreased during the treatment period. Values for HCV viral load showed slight reduction, although not statistically significant (p \ 0.01).
AB174
J AM ACAD DERMATOL
FEBRUARY 2007