role of rheologic alterations on cardiovascular risk of psoriatic patients

1
P6678 Relationship between body regions and PASI clinical components for health-related quality of life: Subanalysis of REVEAL Alexander A. Navarini, MD, University Hospital Zurich, Zurich, Switzerland; Alan Menter, MD, Baylor Research Institute, Dallas, TX, United States; Henrique D. Teixeira, PhD, MBA, Abbott Laboratories, Abbott Park, IL, United States; Yihua Gu, MS, Abbott Laboratories, Abbott Park, IL, United States; Yves Poulin, MD, Center Dermatologique de Quebec Metropolitain, Sainte-Foy, Quebec, Canada Background: To determine the effect of psoriasis area and severity index (PASI) scores for specific body regions and individual PASI components on dermatology life quality index (DLQI) scores. Methods: REVEAL was a 52-week, placebo-controlled phase III trial of patients with moderate to severe psoriasis (NCT00237887). A subanalysis was conducted from the first 16 weeks using combined data from patients who received placebo or adalimumab (80 mg week 0; 40 mg eow from weeks 1 to 15) who also had baseline PASI $ 12 and DLQI $ 6. The mean percent changes at week 16 from baseline in DLQI scores (total) versus PASI response (overall; by body regions including head, trunk, upper and lower extremities; and by individual PASI components including erythema, induration, desquamation and area) were determined. Results: Patients who achieved an overall PASI 100 response experienced a marked improvement in DLQI (mean reduction of 93.6%). Other improvements (mean reductions) in DLQI were: 88.5%, 76.6%, 48.9%, and 19.1% for patients who achieved PASI responses of 90 to \100, 75 to \90, 50 to \75, and 0 to \50, respectively. 82.1% of patients who achieved overall PASI 100 achieved DLQI of 0 or 1. Patients experiencing a worsening in PASI (PASI response \0) experienced a deterioration in DLQI with a mean score increase of 7.3%. For the head region, a higher threshold of PASI response was needed in order to make a significant impact on DLQI: Patients who achieved PASI 100 (head region) showed a mean reduction in DLQI of 82.4%. Other improvements (mean reductions) in DLQI were 67.1%, 59.2%, 41.6%, and 19.5% for patients who achieved PASI 90 to \100, 75 to \90, 50 to \75, and 0 to \50 of the head region, respectively. 60.0% of patients who achieved PASI 100 (head region) achieved DLQI of 0 or 1 versus the 82.1% of patients overall. Improvements in DLQI scores also correlated well with PASI responses observed in the trunk, upper extremities, and lower extremities. Similar results were observed when analyzing the correlations between improvement in DLQI scores with all individual PASI components (erythema, induration, desquamation and area). Conclusion: Correlations exist between all PASI components’ responses (overall; all body regions; and all individual PASI components) with improvements in patients’ DLQI scores. In general, the head is one body region in which a high threshold of PASI response is needed in order to make a significant impact on DLQI scores. 100% is sponsored by Abbott Laboratories. P6804 Resolution of recalcitrant psoriatic plaques after treatment with gemcita- bine and carboplatin Douglas Heiner, MD, Roger Williams Medical Center Department of Dermatology, Providence, RI, United States; Anita Pedvis-Leftick, MD, Roger Williams Medical Center Department of Dermatology, Providence, RI, United States; Christina Cernik, MD, Roger Williams Medical Center Department of Dermatology, Providence, RI, United States We report a 64-year-old woman with generalized chronic plaque psoriasis who showed a complete regression of skin lesions following therapy with gemcitabine and carboplatin for stage IV ovarian papillary serous carcinoma. On presentation, our patient had a 40-year history of plaque type psoriasis with widespread erythematous scaling plaques involving the chest, abdomen, back, buttocks, groin, and extremities. Treatment of the plaques with therapies including topical cortico- steroids, calcipotriene, coal tar distillate, salicylic acid and phototherapy with narrowband UVB were not effective. Furthermore, systemic treatment including methotrexate and etanercept resulted in only partial and transient remission of psoriatic skin lesions. For the patient’s stage IV ovarian papillary serous carcinoma, our patient was given neoadjuvant carboplatin and paclitaxel beginning in April 2010 followed by surgery in July 2010. In July 2011, a positron emission tomography (PET) scan revealed a relapse of disease, and our patient was started on a new anticancer chemotherapy regimen. This consisted of gemcitabine, which had not previously been administered, and carboplatin. Three days following the first infusion of gemcitabine and carboplatin the psoriatic lesions showed partial regression. One week later, after a second infusion with gemcitabine, no psoriatic plaques were visualized. The pathogenesis of psoriasis remains incompletely understood, but the role of a T cellemediated immune response is well recognized. Improvement of psoriasis in patients taking gemcitabine has been reported in only a few instances. To our knowledge, we are the first to report total clearance of widespread psoriatic lesions in a patient on gemcitabine who has previously failed biologic therapy. Gemcitabine is a nucleoside analog that interferes with cell division by being incorporated during DNA replication. There is some evidence for an immunosuppressive action of gemcitabine on T lymphocytes in vitro and in rat models. Taken together, these finding suggest that gemcitabine may exhibit both an inhibitory effect on lymphocytes as well as an antiproliferative effect in the pathogenesis of psoriasis. Further studies investigating the effectiveness of gemcitabine in psoriasis may be useful. Commercial support: None identified. P6690 Risk of developing micro- and macrovascular complications in diabetes patients with psoriasis April W. Armstrong, Sacramento, CA, United States; Annie Gu erin, Boston, MA, United States; Elizabeth Faust, Boston, MA, United States; Murali Sundaram, Abbott Park, IL, United States; Parvez M. Mulani, Abbott Park, IL, United States Objective: To compare the risks of developing diabetes-related micro- and macro- vascular complications between diabetes patients with and without psoriasis (Ps). Methods: Adult patients with $ 2 diabetes diagnoses were selected from the Thomson Reuters MarketScan database (2000-2006). Patients were classified into 2 mutually exclusive cohorts: (1) patients with $ 2 diagnoses for Ps and (2) those without a diagnosis of Ps. Patients with and without Ps were matched based on propensity score and on sex, type of diabetes (I/II), diabetes medications, and previous diabetes-related complications. Risks of microvascular (nephropathy, neuropathy, and retinopathy) and macrovascular (eg, myocardial infarction, heart failure, stroke) complications were studied over 12 months. Patients diagnosed with the studied complication during the 6-month baseline period were excluded. Cox proportional hazards regressions were used to estimate the adjusted hazards ratios (HR) controlling for differences in patient characteristics. The analysis was also stratified by Ps severity for mild (ie, receiving no Ps therapy or only topical therapies) and moderate to severe (ie, receiving phototherapy or systemic therapies) patients and their Ps-free controls. Results: A total of 6277 Ps patients with diabetes (88% mild; 12% moderate to severe) were matched to 6277 Ps-free diabetic patients. Diabetic patients with Ps were significantly more likely to develop micro- (HR ¼ 1.13, P \.001) and macrovascular (HR ¼ 1.09, P ¼.032) complications than were Ps-free diabetic patients. Both mild and moderate to severe Ps patients were significantly more likely to develop microvascular complications than were Ps-free patients (HR ¼ 1.12, P ¼.006 and HR ¼ 1.26, P ¼ .038, respectively). Mild Ps was associated with greater risk of macro- vascular complications compared to Ps-free patients (HR ¼ 1.11, P ¼.011), but no significant difference was found between moderate to severe Ps patients and their controls (HR ¼ 0.92, P ¼.491). Conclusion: Diabetic patients with Ps were more likely to develop micro- and macrovascular complications. However, no significant difference in the risk of macrovascular complications was found between moderate to severe Ps patients and their Ps-free controls. With severity defined by medication use, this finding could be related to the fact that some systemic therapies, such as methotrexate and some biologics, may have protective effects against cardiovascular diseases. This study was funded by Abbott Laboratories. P6723 Role of rheologic alterations on cardiovascular risk of psoriatic patients Veronica Lopez Castillo, MD, Hospital Quiron, Valencia, Spain; Amparo Vaya, MD, Hospital La Fe, Valencia, Spain; Belinda Andino, MD, Hospital La Fe, Valencia, Spain; Cornelio Nu~ nez, MD, Hospital La Fe, Valencia, Spain; Daniel Bautista, MD, Hospital General, Valencia, Spain; Jose Todoli, MD, Hospital La Fe, Valencia, Spain; Jose M Ricart, MD, Hospital Quiron, Valencia, Spain Psoriasis is a systemic inflammatory disorder with increased cardiovascular risk which has been partly attributed to the increased prevalence of the metabolic syndrome (MS) that patients show. However, the contribution of rheologic altera- tions on cardiovascular risk has been scarcely investigated. We have determined in 91 psoriasis patients and in 101 healthy volunteers the rheological profile (fibrin- ogen, blood viscosity and erythrocyte aggregation) along with lipidic and inflam- matory parameters. Patients showed statistically higher BMI, waist, triglycerides, insulin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), neutrophils, lower HDL-cholesterol and a higher prevalence of the MS (P \.05). When subjects with MS were excluded from the study, patients with psoriasis still showed a worse inflammatory, lipidic and rheologic profile in the above mentioned variables compared with controls without MS (P \ .05). The logistic regression analysis revealed that abdominal obesity and fibrinogen [384 mg/dL were independent predictors of psoriasis (OR 3.75 IC 95% 1.77-7.94, P \.001; OR 2.95 IC 95% 1.14- 7.64, P ¼.025 respectively). Patients under biologics (ie, antieTNF-a) showed lower inflammation and a better rheologic profile than those without biologic treatment. The results of the present study indicate that patients with psoriasis show an altered rheologic profile which may contribute to increased cardiovascular risk. Although the presence of the MS worsen this profile, psoriasis ‘‘per se’’ shows rheologic alterations due both to inflammation and to the altered metabolic parameters. AntieTNF-a treatment improves markedly rheologic profile mostly by decreasing inflammation. Dermatologists need to be aware about the metabolic comorbidities accompanying psoriasis in order to early detect the cardiovascular risk in these patients. Commercial support: None identified. AB210 JAM ACAD DERMATOL APRIL 2013

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Page 1: Role of rheologic alterations on cardiovascular risk of psoriatic patients

P6678Relationship between body regions and PASI clinical components forhealth-related quality of life: Subanalysis of REVEAL

Alexander A. Navarini, MD, University Hospital Zurich, Zurich, Switzerland; AlanMenter, MD, Baylor Research Institute, Dallas, TX, United States; Henrique D.Teixeira, PhD, MBA, Abbott Laboratories, Abbott Park, IL, United States; YihuaGu, MS, Abbott Laboratories, Abbott Park, IL, United States; Yves Poulin, MD,Center Dermatologique de Quebec Metropolitain, Sainte-Foy, Quebec, Canada

Background: To determine the effect of psoriasis area and severity index (PASI)scores for specific body regions and individual PASI components on dermatology lifequality index (DLQI) scores.

Methods: REVEAL was a 52-week, placebo-controlled phase III trial of patients withmoderate to severe psoriasis (NCT00237887). A subanalysis was conducted fromthe first 16 weeks using combined data from patients who received placebo oradalimumab (80 mg week 0; 40 mg eow from weeks 1 to 15) who also had baselinePASI $ 12 and DLQI $ 6. The mean percent changes at week 16 from baseline inDLQI scores (total) versus PASI response (overall; by body regions including head,trunk, upper and lower extremities; and by individual PASI components includingerythema, induration, desquamation and area) were determined.

Results: Patients who achieved an overall PASI 100 response experienced a markedimprovement in DLQI (mean reduction of 93.6%). Other improvements (meanreductions) in DLQI were: 88.5%, 76.6%, 48.9%, and 19.1% for patients whoachieved PASI responses of 90 to \100, 75 to \90, 50 to \75, and 0 to \50,respectively. 82.1% of patients who achieved overall PASI 100 achieved DLQI of 0 or1. Patients experiencing a worsening in PASI (PASI response \0) experienced adeterioration in DLQI with a mean score increase of 7.3%. For the head region, ahigher threshold of PASI response was needed in order to make a significant impacton DLQI: Patients who achieved PASI 100 (head region) showed amean reduction inDLQI of 82.4%. Other improvements (mean reductions) in DLQI were 67.1%, 59.2%,41.6%, and 19.5% for patients who achieved PASI 90 to\100, 75 to\90, 50 to\75,and 0 to\50 of the head region, respectively. 60.0% of patients who achieved PASI100 (head region) achieved DLQI of 0 or 1 versus the 82.1% of patients overall.Improvements in DLQI scores also correlated well with PASI responses observed inthe trunk, upper extremities, and lower extremities. Similar results were observedwhen analyzing the correlations between improvement in DLQI scores with allindividual PASI components (erythema, induration, desquamation and area).

Conclusion: Correlations exist between all PASI components’ responses (overall; allbody regions; and all individual PASI components) with improvements in patients’DLQI scores. In general, the head is one body region in which a high threshold ofPASI response is needed in order to make a significant impact on DLQI scores.

AB210

ponsored by Abbott Laboratories.

100% is s

P6804Resolution of recalcitrant psoriatic plaques after treatment with gemcita-bine and carboplatin

Douglas Heiner, MD, Roger Williams Medical Center Department of Dermatology,Providence, RI, United States; Anita Pedvis-Leftick, MD, Roger Williams MedicalCenter Department of Dermatology, Providence, RI, United States; ChristinaCernik, MD, Roger Williams Medical Center Department of Dermatology,Providence, RI, United States

We report a 64-year-old woman with generalized chronic plaque psoriasis whoshowed a complete regression of skin lesions following therapy with gemcitabineand carboplatin for stage IV ovarian papillary serous carcinoma. On presentation,our patient had a 40-year history of plaque type psoriasis with widespreaderythematous scaling plaques involving the chest, abdomen, back, buttocks, groin,and extremities. Treatment of the plaques with therapies including topical cortico-steroids, calcipotriene, coal tar distillate, salicylic acid and phototherapy withnarrowband UVB were not effective. Furthermore, systemic treatment includingmethotrexate and etanercept resulted in only partial and transient remission ofpsoriatic skin lesions. For the patient’s stage IV ovarian papillary serous carcinoma,our patient was given neoadjuvant carboplatin and paclitaxel beginning in April2010 followed by surgery in July 2010. In July 2011, a positron emission tomography(PET) scan revealed a relapse of disease, and our patient was started on a newanticancer chemotherapy regimen. This consisted of gemcitabine, which had notpreviously been administered, and carboplatin. Three days following the firstinfusion of gemcitabine and carboplatin the psoriatic lesions showed partialregression. One week later, after a second infusion with gemcitabine, no psoriaticplaques were visualized. The pathogenesis of psoriasis remains incompletelyunderstood, but the role of a T cellemediated immune response is well recognized.Improvement of psoriasis in patients taking gemcitabine has been reported in only afew instances. To our knowledge, we are the first to report total clearance ofwidespread psoriatic lesions in a patient on gemcitabine who has previously failedbiologic therapy. Gemcitabine is a nucleoside analog that interferes with celldivision by being incorporated during DNA replication. There is some evidence foran immunosuppressive action of gemcitabine on T lymphocytes in vitro and in ratmodels. Taken together, these finding suggest that gemcitabine may exhibit both aninhibitory effect on lymphocytes as well as an antiproliferative effect in thepathogenesis of psoriasis. Further studies investigating the effectiveness ofgemcitabine in psoriasis may be useful.

cial support: None identified.

Commer

J AM ACAD DERMATOL

P6690Risk of developing micro- and macrovascular complications in diabetespatients with psoriasis

April W. Armstrong, Sacramento, CA, United States; Annie Gu�erin, Boston, MA,United States; Elizabeth Faust, Boston, MA, United States; Murali Sundaram,Abbott Park, IL, United States; Parvez M. Mulani, Abbott Park, IL, United States

Objective: To compare the risks of developing diabetes-related micro- and macro-vascular complications between diabetes patients with and without psoriasis (Ps).

Methods: Adult patients with $ 2 diabetes diagnoses were selected from theThomson Reuters MarketScan database (2000-2006). Patients were classified into 2mutually exclusive cohorts: (1) patients with $ 2 diagnoses for Ps and (2) thosewithout a diagnosis of Ps. Patients with and without Ps were matched based onpropensity score and on sex, type of diabetes (I/II), diabetes medications, andprevious diabetes-related complications. Risks of microvascular (nephropathy,neuropathy, and retinopathy) and macrovascular (eg, myocardial infarction, heartfailure, stroke) complications were studied over 12 months. Patients diagnosed withthe studied complication during the 6-month baseline period were excluded. Coxproportional hazards regressions were used to estimate the adjusted hazards ratios(HR) controlling for differences in patient characteristics. The analysis was alsostratified by Ps severity for mild (ie, receiving no Ps therapy or only topical therapies)and moderate to severe (ie, receiving phototherapy or systemic therapies) patientsand their Ps-free controls.

Results: A total of 6277 Ps patients with diabetes (88%mild; 12%moderate to severe)were matched to 6277 Ps-free diabetic patients. Diabetic patients with Ps weresignificantly more likely to develop micro- (HR ¼ 1.13, P\.001) and macrovascular(HR ¼ 1.09, P ¼ .032) complications than were Ps-free diabetic patients. Both mildand moderate to severe Ps patients were significantly more likely to developmicrovascular complications than were Ps-free patients (HR¼ 1.12, P¼.006 and HR¼ 1.26, P ¼ .038, respectively). Mild Ps was associated with greater risk of macro-vascular complications compared to Ps-free patients (HR ¼ 1.11, P ¼ .011), but nosignificant difference was found between moderate to severe Ps patients and theircontrols (HR ¼ 0.92, P ¼ .491).

Conclusion: Diabetic patients with Ps were more likely to develop micro- andmacrovascular complications. However, no significant difference in the risk ofmacrovascular complications was found between moderate to severe Ps patientsand their Ps-free controls. With severity defined by medication use, this findingcould be related to the fact that some systemic therapies, such as methotrexate andsome biologics, may have protective effects against cardiovascular diseases.

y was funded by Abbott Laboratories.

This stud

P6723Role of rheologic alterations on cardiovascular risk of psoriatic patients

Veronica Lopez Castillo, MD, Hospital Quiron, Valencia, Spain; Amparo Vaya, MD,Hospital La Fe, Valencia, Spain; Belinda Andino, MD, Hospital La Fe, Valencia,Spain; Cornelio Nu~nez, MD, Hospital La Fe, Valencia, Spain; Daniel Bautista, MD,Hospital General, Valencia, Spain; Jose Todoli, MD, Hospital La Fe, Valencia,Spain; Jose M Ricart, MD, Hospital Quiron, Valencia, Spain

Psoriasis is a systemic inflammatory disorder with increased cardiovascular riskwhich has been partly attributed to the increased prevalence of the metabolicsyndrome (MS) that patients show. However, the contribution of rheologic altera-tions on cardiovascular risk has been scarcely investigated. We have determined in91 psoriasis patients and in 101 healthy volunteers the rheological profile (fibrin-ogen, blood viscosity and erythrocyte aggregation) along with lipidic and inflam-matory parameters. Patients showed statistically higher BMI, waist, triglycerides,insulin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), neutrophils,lower HDL-cholesterol and a higher prevalence of the MS (P\.05). When subjectswith MS were excluded from the study, patients with psoriasis still showed a worseinflammatory, lipidic and rheologic profile in the above mentioned variablescompared with controls without MS (P \ .05). The logistic regression analysisrevealed that abdominal obesity and fibrinogen [384 mg/dL were independentpredictors of psoriasis (OR 3.75 IC 95% 1.77-7.94, P\.001; OR 2.95 IC 95% 1.14-7.64, P¼.025 respectively). Patients under biologics (ie, antieTNF-a) showed lowerinflammation and a better rheologic profile than those without biologic treatment.The results of the present study indicate that patients with psoriasis show an alteredrheologic profile which may contribute to increased cardiovascular risk. Althoughthe presence of the MS worsen this profile, psoriasis ‘‘per se’’ shows rheologicalterations due both to inflammation and to the altered metabolic parameters.AntieTNF-a treatment improves markedly rheologic profile mostly by decreasinginflammation. Dermatologists need to be aware about the metabolic comorbiditiesaccompanying psoriasis in order to early detect the cardiovascular risk in thesepatients.

cial support: None identified.

Commer

APRIL 2013