P6560Cardiovascular safety in the ustekinumab clinical development program:Final update with up to 5 years of follow-up

Kristian Reich, MD, Dermatologikum Hamburg, Hamburg, Germany; C. E. M.Griffiths, MD, University of Manchester, Manchester, United Kingdom; MarkLebwohl, MD, Mount Sinai School of Medicine, New York, NY, United States;Philippe Szapary, MD, Janssen Research and Development, LLC, Spring House,PA, United States

Objective: To report the rates of adjudicated major CV adverse events (MACE)observed in the ustekinumab (UST) psoriasis clinical development program with upto 5 years of follow-up.

Methods: Data were pooled across UST psoriasis trials [phase II trial (n ¼ 320),ACCEPT (n ¼ 903), PHOENIX1 (n ¼ 766), and PHOENIX2 (n ¼ 1230)], including3117 UST-treated patients (8998 patient-years of follow-up [PY]). The ClevelandClinic Coordinating Center for Clinical Research performed retrospective blindedadjudication of serious adverse events that might represent MACE (CV death,myocardial infarction, or stroke). Cumulative rates of adjudicated MACE per 100 PY(95%CI) were evaluated by dose and over time. A KaplaneMeier (KM) time-to-firstevent analysis further evaluated the rate of MACE over time with increasingexposure to UST. Standardized incidence ratios (SIRs, 95% CI) were used to compareobserved rates of MI and stroke in UST-treated patients to rates expected in a generalUS population (Framingham Heart Study [FHS]), and a UK psoriasis (systemically-treated) population (General Practice Research Database [GPRD]); adjusted forbaseline CV risk factors (age, gender, hypertension, hyperlipidemia, diabetesmellitus, and smoking status).

Results: With up to 5 years of follow-up, the rates of MACE per 100 PY (95%CI) forthe UST 45 mg, UST 90 mg, and combined UST groups were 0.56 (0.35, 0.85) and0.36 (0.22, 0.57), and 0.44 (0.32, 0.61), respectively. Event rates per 100 PY (95% CI)by year of follow-up in the combined UST groups were 0.47 (0.24, 0.82), 0.36 (0.13,0.79), 0.46 (0.19, 0.96), 0.56 (0.24, 1.10), and 0.37 (0.15, 0.77) for years 1, 2, 3, 4,and 5, respectively. KM analysis indicated event distribution throughout the entireobservation period, with a generally linear increase of\1% per yr and cumulativerate of \2% over 5 years. The number of patients with MI and stroke eventsobserved among UST-treated group were comparable to that expected in matched-controls from the FHS population (observed ¼ 31, expected ¼ 64.93, SIR ¼ 0.48[0.32, 0.68]) andmatched-psoriasis controls fromGPRD population (observed¼ 31,expected ¼ 91.34, SIR ¼ 0.34 [0.23, 0.48]).

Conclusion: With up to 5 years of follow-up, MACE rates remained stable over timeand consistent with previous reports, without an observed dose response. Observedrates of MI and stroke in UST-treated patients were consistent with that expected in ageneral and psoriasis populations, although comparisons with external, non-clinicaltrial databases are associated with limitations.

AB194

d by Janssen Services, LLC.

Supporte

P6975Foundation panel surveys

Emily Edson-Heredia, MPH, Eli Lilly and Company, Indianapolis, IN, UnitedStates; Baojin Zhu, PhD, Eli Lilly and Company, Indianapolis, IN, United States;Jiaying Guo, MS, PharmaNet i3, Indianapolis, IN, United States; Mark Lebwohl,MD, The Mount Sinai School of Medicine, New York, NY, United States

Objective: This study compared patient characteristics, comorbidity, and psoriaticdisease impact in patients with moderate to severe psoriasis either with or withoutpsoriatic arthritis.

Methods: Adult patients with moderate to severe plaque psoriasis were identified ina dataset of combined National Psoriasis Foundation (NPF) panel surveys conductedfrom 2003 through 2011. Two cohorts were created based on self reported psoriaticarthritis (PsA) diagnosis. Patient-reported data on sociodemographic and diseasecharacteristics were collected along with treatment satisfaction and PsoriasisQuality of Life Questionnaire (PQOL) responses. Variables on patient characteristicsand comorbid conditions were compared between cohorts using student t-tests andchi square tests for continuous and categorical variables, respectively. Treatmentsatisfaction, PQOL total score, and PQOL symptom variables were comparedbetween cohorts using a generalized linear model adjusted for age, gender, race,duration of disease, and psoriasis severity.

Results: A total of 3532 patients with moderate to severe psoriasis were identified,1280 (36.2%) of whom had PsA. In comparison to psoriasis patients without PsA,those with PsA were significantly (P\.05 for all comparisons) older (51.7 vs 48.8years old), less likely to be employed (52.7% vs 63.0%), more likely to be female(64.0% vs 57.4%), had longer duration of disease (24.8 vs 20.9 years), andmore likelyto have health insurance coverage (91.6% vs 88.6%). Psoriatic arthritis patientsreported more comorbid diabetes (15.6% vs 9.4%) and high blood pressure (40.0%vs 32.4%) compared with psoriasis patients without PsA. Patients with PsA alsoreported worse disease impact in terms of PQOL score, itching, physicalirritation/soreness, and pain severity, yet greater treatment satisfaction comparedto patients without PsA.

Conclusion: Patients withmoderate to severe plaque psoriasis and comorbid PsA area complex patient population. Our findings suggest these patients may be at greaterrisk for cardiovascular disease and worse psoriatic disease impact as compared topatients with moderate to severe plaque psoriasis but without coexisting PsA.

nsored by Eli Lilly and Company.

100% spo

J AM ACAD DERMATOL

P6595Characteristics of psoriasis patients with self-assessed limited diseasecontrol despite physician-assessed clear or minimal skin disease

Alexa B. Kimball, Harvard Medical School, Boston, MA, United States; James E.Signorovitch, Analysis Group, Inc, Boston, MA, United States; Murali Sundaram,Global Health Economics and Outcomes Research, Abbott Laboratories, AbbottPark, IL, United States; Thomas Samuelson, Analysis Group Inc, Boston, MA,United States

Objective: To characterize psoriasis (Ps) patients with self-assessed limited diseasecontrol despite clear or minimal skin disease.

Methods: Patients with moderate to severe Ps treated with biologics (adalimumaband etanercept), methotrexate, or placebo were drawn from clinical trials:BELIEVE, CHAMPION, M10-114, M10-255, M10-315, REVEAL. Patient visits with aPhysician’s Global Assessment (PGA) of ‘‘clear’’ or ‘‘minimal’’ were identified. Amongthese visits, the subgroup with a Patient’s Global Assessment (PtGA) of ‘‘uncon-trolled disease’’ or ‘‘limited disease control’’ was identified. A multivariate logisticregression model was constructed to identify patient characteristics associatedwith self-assessed limited/uncontrolled disease despite a PGA of clear/minimal.Characteristics considered included age, weight, sex, Ps duration, history ofpsoriatic arthritis, pretrial use of systemic biologics, pretrial use of nonbiologicsystemics, familial history of Ps, current joint inflammation (yes/no), Ps or psoriaticarthritiserelated pain (on a visual analog scale [VAS] of 0-100), Ps-related pruritus(on a scale of 0-10), the Psoriasis Area and Severity Index, current PGA level (clear orminimal) and prevalent comorbidities, including blood irregularities, cardiovasculardisease, gastrointestinal disease, depression, diabetes, hyperlipidemia, hypertensionand obesity.

Results: 534 of 11,015 patient visits had a PGA of clear and 1725 a PGA of minimal.Of these 2259 visits, 60 visits had a PtGA of uncontrolled disease and 450 visits hadlimited disease control. In patients with PGA of clear or minimal, pain, pruritus, andcurrent joint inflammation were significantly associated with increased odds ofpatient-assessed limited disease control or uncontrolled disease. Pain (10 mm onVAS) was associated with a 12% increase (odds ratio [OR]: 1.12; 95% confidenceinterval [CI]: 1.01-1.23; P ¼ .027); pruritus (1 unit) was associated with a 49%increase (OR: 1.49; 95% CI: 1.38e1.60; P\.001), and current joint inflammationwas associated with a 67% increase (OR: 1.67; 95% CI: 1.19e2.34; P¼.003) of PtGAof limited/uncontrolled disease among patients with clear or minimal PGA.

Conclusion: In Ps patients with physician-assessed clear or minimal skin disease,pain, pruritus, and joint inflammation may persist, and are associated with limiteddisease control from the patient’s perspective. Complete management of Ps shouldinclude assessment of these signs and symptoms.

y was funded by Abbott Laboratories.

This stud

P6971Chronic psoriatic plaques contain newly identified CCL20-producingTH1/TH17/TH22 subsets and clusters of CCR6+DC-LAMP+ mature myeloiddendritic cells: A possible pathogenic role of CCL20/CCR6 chemokinesystem in T cells/DCS interaction

Hyunjoong Jee, MD, Department of Dermatology and Cutaneous BiologyResearch Institute, Yonsei University College of Medicine, Seoul, Korea;Dashlkhumbe Byamba, MD, Department of Dermatology and CutaneousBiology Research Institute, Yonsei University College of Medicine, Seoul,Korea; Do-Young Kim, MD, Department of Dermatology and CutaneousBiology Research Institute, Yonsei University College of Medicine, Seoul,Korea; Min-Geol Lee, MD, PhD, Department of Dermatology and CutaneousBiology Research Institute, Yonsei University College of Medicine, Seoul, Korea;Tae-Gyun Kim, MD, Department of Dermatology and Cutaneous BiologyResearch Institute, Yonsei University College of Medicine, Seoul, Korea

Psoriasis is a chronic T cellemediated inflammatory cutaneous disorder.Histopathologically an increase in lesional inflammatory cells, such as T cells anddendritic cells (DCs), is easily identified. The chemokine receptors have emerged asimportant determinants for the phenotypical characterization of distinct T cellsubsets. A number of chemokines and receptors have been well-studied on T cells;however, it is not well understood so far which chemokine receptors are expressedon the lesional DCs. In this study, we explored the expression of chemokinereceptors on the lesional DCs in psoriasis. Although CCR1+ cells are not increased innumber in psoriatic lesional skin compared to normal skin, CCR6+ and CCR7+ cellsare increased significantly and they present a grouping feature. CCR6+ cells inpsoriatic plaques include myeloid DCs, T cells, and, unexpectedly, DC-LAMP+

mature DCs. Via FACS analysis using dermal single-cell suspensions, we confirmedhigh expression of CCR6 on DC-LAMP+ mature DCs; however, DC-LAMP- DCs aredevoid of CCR6 expression. Using 2-color immunofluorescence, we confirmed thatpsoriatic lesional T cells express CCR6 ligand, CCL20, and DC-LAMP+ cells are foundclose to CCL20+ cells which suggest CCL20/CCR6 interaction between lesional Tcells and DC-LAMP+ mature DCs. In addition, we newly identified that CCL20-producing T cells are TH1/TH17/TH22 subsets, but not TH2 subset. Collectively wepropose the novel concept that a population of lesional CCL20-producingTH1/TH17/TH22 cells closely contact CCR6+ mature DCs, so that lesional T cellscan be persistently activated and further recruit CCR6+DC-LAMP+ DCs and CCR6+

TH17 cells to maintain the chronicity.

Keywords: CCL20, CCR6, DC-LAMP mature DC, psoriasis

cial support: None identified.

Commer

APRIL 2013