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Analysis of major adverse cardiovascular events in the Psoriasis Longitudinal Assessment and Registry Study (PSOLAR)
2887
3728
An innovative topical therapy for the palmoplantar hyperkeratosis Antonio Carpentieri, Policlinico di Bari, Bari, Italy; Lorenzo Mossa, Policlinico Bari, Bari, Italy; Fabrizio Favero, Policlinico Bari, Italy; Francesco Loconsole, Policlinico Bari A study on the topical treatment of the palmoplantar hyperkeratosis in 25 subjects of 18 years of age and above, both males and females, selected between January and June 2015 was carried out at the psoriasis outpatient clinic of the Dermatological Department of the University of Bari, Italy. The selected sample consisted for the 84% (21 patients) of individuals affected by palmoplantar psoriasis, mainly characterized by scaling and hyperkeratosis with mild erythema and infiltration; the remaining 16% (4 patients) was divided as follows: 75% (3 patients) of subjects was affected by chronic hand eczema, mainly characterized by a squamous hyperkeratosis morphology, 25% (1 patient) was affected by pityriasis rubra pilaris with the typical clinical picture of palmoplantar keratoderma with a yellow-orange chromatic shade. The tested product consists of sodium lactate, at a concentration of 30%, of which the keratolytic, elasticizing, emollient properties and the capacity to promote the correct regeneration of the cutaneous tissue were evaluated. For each patient, a technical card was filled out to quantify, according to the physician’s judgement, the following cutaneous parameters before and after 2 months of therapy: degree of xerosis, thickening, and scaling. The study has provided the possibility to evaluate considerable clinical improvements with respect to the considered parameters. Through the DLQI test (Dermatology Quality of Life Index), administered before and after therapy, it was also possible to assess the improvement of the quality of life in patients at the end of the treatment. The importance of this study stems from the necessity to treat, with the highest specificity, all of those cases of palmoplantar desquamating hyperkeratosis that, associated to several dermatosis, severely affect activities like the grip and the walking abilities, and have a strong impact on the quality of life both in the professional and social environment.
Assessment of HLA Cw6 genotype and correlation to ustekinumab response in a large cohort of patients with moderate-to-severe psoriasis Katherine Li, PhD, Janssen Research and Development, LLC, Spring House, PA, United States; Chris Huang, PhD, Janssen Research and Development, LLC, Spring House, PA, United States; Yasmine Wasfi, MD, Janssen Research and Development, LLC, Spring House, PA, United States; Bruce Randazzo, MD, Janssen Research and Development. LLC, Spring House, PA, United States; Shu Li, PhD, Janssen Research and Development, LLC, Spring House, PA, United States; Philippe Szapary, MD, Janssen Research and Development, LLC, Spring House, PA, United States; Kim Campbell, PhD, Janssen Research and Development, LLC, Spring House, PA, United States; Carrie Brodmerkel, PhD, Janssen Research and Development, LLC, Spring House, PA, United States Objectives: The link between the HLA-Cw6 allele in psoriasis (PsO) patients (pts) and improved clinical response to ustekinumab (UST) therapy was reported previously (Talamonti et al). The aim of this retrospective analysis was to determine the association of HLA-Cw6 status and response to UST in a large, well-controlled clinical trial population. Methods: DNA was collected from approximately 600 North American participants in the UST Phoenix 1, Phoenix 2, and ACCEPT Ph3 PsO clinical trials. HLA-Cw6 genotype was assessed by SNP-chip imputation then correlated to PASI and PGA responses. Association between HLA-Cw6 status and efficacy (short and long-term) of UST or likelihood for dose escalation was evaluated.
Commercial support: None identified.
Results: The prevalence of HLA-Cw6 was 44.6%. The HLA-Cw6 genotype in this combined population was associated with longer disease duration and earlier age of disease onset. Both HLA Cw6 positive as well as negative pts demonstrated relatively high response rates to UST (wk24 PASI75 responses were 86% vs 76%, respectively). A modestly higher percentage of HLA-Cw6 positive pts achieved PASI 50, 75, 90 and 100 at wks 4, 12, 24, and 28, vs HLA-Cw6 negative pts. The largest delta between positive and negative pts (17.9%) was observed for PASI75 response at wk12 with smaller differences noted at later timepoints for PASI90 (11.8% at wk24) and PASI100 (10.2% at wk28) response rates. HLA-Cw6 positive pts had modestly higher long-term efficacy rates than those that were HLA-Cw6 negative with statistical significance reached for PASI75 response rates (82.6% vs 64.4%, respectively) at the 5 year final efficacy assessment in Phoenix 1. Lastly, a larger percentage of HLA-Cw6 negative pts underwent a shortened dosing interval and/or dose escalation through year 5 in Phoenix 2. 57% of HLA-Cw6 positive pts did not require dose escalation vs 50% of negative. Among pts who received initial treatment of UST 45 mg, 41% of negative and 32% of HLA-Cw6 positive pts required both dose escalation and dose interval adjustment. Conclusions: While a differential response to UST is evident in HLA-Cw6 positive vs HLA-Cw6 negative pts, the difference is modest particularly for response rates of more complete responses (PASI90 and PASI100); thus, the clinical utility of this marker as a predictor of response to UST appears to be limited. Supported 100% by Janssen Research and Development, LLC.
3229 Analysis of major adverse cardiovascular events in the Psoriasis Longitudinal Assessment and Registry Study (PSOLAR) Robert Bissonnette, MD, Innovaderm Research, Inc, Montreal, Quebec, Canada; Alice Gottlieb, MD, Tufts Medical Center, Boston, MA, United States; Francisco Kerdel, MD, Florida Academic Dermatology Centers, Miami, FL, United States; Luigi Naldi, MD, Centro Studi GISED, Ospendali Riuniti, Bergamo, Italy; Kim Papp, MD, K. Papp Clinical Research and Probity Medical Research, Waterloo, Ontario, Canada; Steve Calabro, MBA, Janssen Scientific Affairs, LLC, Horsham, PA, United States; Wayne Langholff, PhD, Janssen Scientific Affairs, LLC, Horsham, PA, United States; Steve Fakharzadeh, MD, Janssen Scientific Affairs, LLC, Horsham, PA, United States; Kavitha Goyal, MD, Janssen Scientific Affairs, LLC, Horsham, PA, United States Objective: To compare the risk of MACE in psoriasis patients with new or ongoing exposure to biologic (bio) therapy vs topical/phototherapy (top/photo). Methods: PSOLAR is an international psoriasis registry which follows patients who are eligible to receive systemic therapy based on standards of clinical practice. MACE is defined as cardiovascular death, stroke, and myocardial infarction. Cohorts were developed for new and ongoing use of all bios combined, TNFIs, ustekinumab separately, and top/photo, and observed through Aug 23, 2014; MTX was excluded from all groups. Demographics and clinical characteristics are described. Cumulative incidence rates in 100/PY with 95% CIs are summarized. Cox hazard regression methodology was used to identify risk factors, including bio therapies, for first MACE; with a reference group of top/photo. Results: Data were analyzed from 7666 pts (6835 bio-exposed, 831 top/photoexposed) for 19006 pt years. Demographics, clinical characteristics, and observation time were generally comparable among bio cohorts. Top/photo cohort was slightly older in age, lighter in weight, and was balanced with respect to gender in context of the bio cohorts. The cumulative incidence rates of MACE for combined bios, TNFIs and ustekinumab respectively were in per 100 PY (95%CI): 0.22 (0.15-0.30), 0.23 (0.15-0.35), and 0.19 (0.10-0.33). Multivariate analysis showed that increasing age (HR 1.78, P \.0001), male gender (HR 2.57, P ¼.0098), and history of hypertension (HR 2.534, P ¼ .0078) were associated with increased risk of MACE. HRs for combined bios, TNFis and ustekinumab respectively were: 0.648, 0.727, 0.526, but did not reach statistical significance. Limitations: Bias in observational data, mismatched populations, unmeasured clinical variability (eg, meds and biomarkers), and inability to detect small differences in risk. Conclusions: Results from PSOLAR suggest a nonsignificant decreased risk with TNFIs or ustekinumab in comparison with top/photo therapy in patients with psoriasis. Supported 100% by Janssen Scientific Affairs, LLC.
AB236
J AM ACAD DERMATOL
MAY 2016
3728
An innovative topical therapy for the palmoplantar hyperkeratosis Antonio Carpentieri, Policlinico di Bari, Bari, Italy; Lorenzo Mossa, Policlinico Bari, Bari, Italy; Fabrizio Favero, Policlinico Bari, Italy; Francesco Loconsole, Policlinico Bari A study on the topical treatment of the palmoplantar hyperkeratosis in 25 subjects of 18 years of age and above, both males and females, selected between January and June 2015 was carried out at the psoriasis outpatient clinic of the Dermatological Department of the University of Bari, Italy. The selected sample consisted for the 84% (21 patients) of individuals affected by palmoplantar psoriasis, mainly characterized by scaling and hyperkeratosis with mild erythema and infiltration; the remaining 16% (4 patients) was divided as follows: 75% (3 patients) of subjects was affected by chronic hand eczema, mainly characterized by a squamous hyperkeratosis morphology, 25% (1 patient) was affected by pityriasis rubra pilaris with the typical clinical picture of palmoplantar keratoderma with a yellow-orange chromatic shade. The tested product consists of sodium lactate, at a concentration of 30%, of which the keratolytic, elasticizing, emollient properties and the capacity to promote the correct regeneration of the cutaneous tissue were evaluated. For each patient, a technical card was filled out to quantify, according to the physician’s judgement, the following cutaneous parameters before and after 2 months of therapy: degree of xerosis, thickening, and scaling. The study has provided the possibility to evaluate considerable clinical improvements with respect to the considered parameters. Through the DLQI test (Dermatology Quality of Life Index), administered before and after therapy, it was also possible to assess the improvement of the quality of life in patients at the end of the treatment. The importance of this study stems from the necessity to treat, with the highest specificity, all of those cases of palmoplantar desquamating hyperkeratosis that, associated to several dermatosis, severely affect activities like the grip and the walking abilities, and have a strong impact on the quality of life both in the professional and social environment.
Assessment of HLA Cw6 genotype and correlation to ustekinumab response in a large cohort of patients with moderate-to-severe psoriasis Katherine Li, PhD, Janssen Research and Development, LLC, Spring House, PA, United States; Chris Huang, PhD, Janssen Research and Development, LLC, Spring House, PA, United States; Yasmine Wasfi, MD, Janssen Research and Development, LLC, Spring House, PA, United States; Bruce Randazzo, MD, Janssen Research and Development. LLC, Spring House, PA, United States; Shu Li, PhD, Janssen Research and Development, LLC, Spring House, PA, United States; Philippe Szapary, MD, Janssen Research and Development, LLC, Spring House, PA, United States; Kim Campbell, PhD, Janssen Research and Development, LLC, Spring House, PA, United States; Carrie Brodmerkel, PhD, Janssen Research and Development, LLC, Spring House, PA, United States Objectives: The link between the HLA-Cw6 allele in psoriasis (PsO) patients (pts) and improved clinical response to ustekinumab (UST) therapy was reported previously (Talamonti et al). The aim of this retrospective analysis was to determine the association of HLA-Cw6 status and response to UST in a large, well-controlled clinical trial population. Methods: DNA was collected from approximately 600 North American participants in the UST Phoenix 1, Phoenix 2, and ACCEPT Ph3 PsO clinical trials. HLA-Cw6 genotype was assessed by SNP-chip imputation then correlated to PASI and PGA responses. Association between HLA-Cw6 status and efficacy (short and long-term) of UST or likelihood for dose escalation was evaluated.
Commercial support: None identified.
Results: The prevalence of HLA-Cw6 was 44.6%. The HLA-Cw6 genotype in this combined population was associated with longer disease duration and earlier age of disease onset. Both HLA Cw6 positive as well as negative pts demonstrated relatively high response rates to UST (wk24 PASI75 responses were 86% vs 76%, respectively). A modestly higher percentage of HLA-Cw6 positive pts achieved PASI 50, 75, 90 and 100 at wks 4, 12, 24, and 28, vs HLA-Cw6 negative pts. The largest delta between positive and negative pts (17.9%) was observed for PASI75 response at wk12 with smaller differences noted at later timepoints for PASI90 (11.8% at wk24) and PASI100 (10.2% at wk28) response rates. HLA-Cw6 positive pts had modestly higher long-term efficacy rates than those that were HLA-Cw6 negative with statistical significance reached for PASI75 response rates (82.6% vs 64.4%, respectively) at the 5 year final efficacy assessment in Phoenix 1. Lastly, a larger percentage of HLA-Cw6 negative pts underwent a shortened dosing interval and/or dose escalation through year 5 in Phoenix 2. 57% of HLA-Cw6 positive pts did not require dose escalation vs 50% of negative. Among pts who received initial treatment of UST 45 mg, 41% of negative and 32% of HLA-Cw6 positive pts required both dose escalation and dose interval adjustment. Conclusions: While a differential response to UST is evident in HLA-Cw6 positive vs HLA-Cw6 negative pts, the difference is modest particularly for response rates of more complete responses (PASI90 and PASI100); thus, the clinical utility of this marker as a predictor of response to UST appears to be limited. Supported 100% by Janssen Research and Development, LLC.
3229 Analysis of major adverse cardiovascular events in the Psoriasis Longitudinal Assessment and Registry Study (PSOLAR) Robert Bissonnette, MD, Innovaderm Research, Inc, Montreal, Quebec, Canada; Alice Gottlieb, MD, Tufts Medical Center, Boston, MA, United States; Francisco Kerdel, MD, Florida Academic Dermatology Centers, Miami, FL, United States; Luigi Naldi, MD, Centro Studi GISED, Ospendali Riuniti, Bergamo, Italy; Kim Papp, MD, K. Papp Clinical Research and Probity Medical Research, Waterloo, Ontario, Canada; Steve Calabro, MBA, Janssen Scientific Affairs, LLC, Horsham, PA, United States; Wayne Langholff, PhD, Janssen Scientific Affairs, LLC, Horsham, PA, United States; Steve Fakharzadeh, MD, Janssen Scientific Affairs, LLC, Horsham, PA, United States; Kavitha Goyal, MD, Janssen Scientific Affairs, LLC, Horsham, PA, United States Objective: To compare the risk of MACE in psoriasis patients with new or ongoing exposure to biologic (bio) therapy vs topical/phototherapy (top/photo). Methods: PSOLAR is an international psoriasis registry which follows patients who are eligible to receive systemic therapy based on standards of clinical practice. MACE is defined as cardiovascular death, stroke, and myocardial infarction. Cohorts were developed for new and ongoing use of all bios combined, TNFIs, ustekinumab separately, and top/photo, and observed through Aug 23, 2014; MTX was excluded from all groups. Demographics and clinical characteristics are described. Cumulative incidence rates in 100/PY with 95% CIs are summarized. Cox hazard regression methodology was used to identify risk factors, including bio therapies, for first MACE; with a reference group of top/photo. Results: Data were analyzed from 7666 pts (6835 bio-exposed, 831 top/photoexposed) for 19006 pt years. Demographics, clinical characteristics, and observation time were generally comparable among bio cohorts. Top/photo cohort was slightly older in age, lighter in weight, and was balanced with respect to gender in context of the bio cohorts. The cumulative incidence rates of MACE for combined bios, TNFIs and ustekinumab respectively were in per 100 PY (95%CI): 0.22 (0.15-0.30), 0.23 (0.15-0.35), and 0.19 (0.10-0.33). Multivariate analysis showed that increasing age (HR 1.78, P \.0001), male gender (HR 2.57, P ¼.0098), and history of hypertension (HR 2.534, P ¼ .0078) were associated with increased risk of MACE. HRs for combined bios, TNFis and ustekinumab respectively were: 0.648, 0.727, 0.526, but did not reach statistical significance. Limitations: Bias in observational data, mismatched populations, unmeasured clinical variability (eg, meds and biomarkers), and inability to detect small differences in risk. Conclusions: Results from PSOLAR suggest a nonsignificant decreased risk with TNFIs or ustekinumab in comparison with top/photo therapy in patients with psoriasis. Supported 100% by Janssen Scientific Affairs, LLC.
AB236
J AM ACAD DERMATOL
MAY 2016