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Serious infection events in the psoriasis longitudinal assessment and registry (PSOLAR) study: Current status of observations
P6508
P6554
Secukinumab treatment shows a neutral impact on the lipid profile of patients with moderate to severe plaque psoriasis in a dose-ranging study Sandra Philipp, Charite-Universit€atsmedizin Berlin, Berlin, Germany; Cesar Escrig, Novartis Pharma AG, Basel, Switzerland; Charis Papavassilis, Novartis Pharma AG, Basel, Switzerland; Diamant Thac¸i, Goethe-University, Frankfurt, Germany; Helen Thurston, Novartis Pharma AG, Basel, Switzerland
Serum chemokine profile in psoriasis Xinaida Lima, MD, MPH, State University of Campinas - UNICAMP, Campinas - S~ao Paulo, Brazil; Fernanda Braga, MS, State University of Campinas - UNICAMP, Campinas - S~ao Paulo, Brazil; Maria Heloisa Blotta, PhD, State University of Campinas - UNICAMP, Campinas - S~ao Paulo, Brazil; Renata Magalh~aes, MD, PhD, State University of Campinas - UNICAMP, Campinas - S~ao Paulo, Brazil; Ronei Mamoni, PhD, State University of Campinas - UNICAMP, Campinas - S~ao Paulo, Brazil Background: The chemokines CXCL9 and CXCL10 interact with receptor CXCR3; and CXCL16 binds to CXCR6. These receptors are implicated in skin homing. Previous studies have shown increased serum levels of CXCL9 and CXCL10 in autoimmune disorders, including psoriatic arthritis (CXCL10). A recent study showed upregulation of CXCL16 in psoriatic lesional skin, but not in the serum. The aim of our study was to evaluate these chemokine ligands in psoriasis.
Background: Psoriasis is a chronic, immune-mediated skin disorder associated with increased levels of interleukin (IL)-17A. Secukinumab, a fully human antieIL-17A monoclonal antibody, has shown therapeutic potential in treatment of plaque psoriasis. In this phase II, double-blind, placebo-controlled trial, we report the effect of secukinumab on the lipid profile of patients with moderate to severe plaque psoriasis. Methods: Patients (N ¼ 404) were randomized (1:2:2:1) to either placebo (n ¼ 67) or one of the 3 subcutaneous secukinumab 150-mg regimens: single (week 0; n ¼ 66), early (weeks 0, 1, 2, 4; n ¼ 133), and monthly (weeks 0, 4, 8; n ¼ 138). Following a 12-week induction period, PASI 75 responders were further randomized (1:1) to 2 maintenance regimens for 20 weeks: the fixed-interval regimen (n ¼ 65; secukinumab 150 mg at weeks 12 and 24) or the treatment at start-of-relapse regimen (n ¼ 67; secukinumab 150 mg during visits at which start of relapse was observed). Nonresponders (not achieving PASI 50), partial responders (achieving PASI 50 but not PASI 75), and patients with 2 consecutive relapses entered the open label phase (secukinumab 150 mg every 4 weeks up to week 32). Patients were followed up for 12 weeks after the last dose. Results: Baseline disease characteristics were comparable between treatment groups. Secukinumab had a neutral effect on the lipid profile of patients compared with placebo and this was maintained throughout the study period. Mean change 6 SD (mmol/L) from baseline to last visit in the induction period or follow-up period for secukinumab single, monthly, early regimens in TC (-0.004 6 0.69, 0.102 6 0.64, 0.122 6 0.73), HDLc (0.012 6 0.19, 0.005 6 0.17, 0.005 6 0.23), LDLc (-0.020 6 0.52, 0.066 6 0.54, 0.025 6 0.65), and TG (0.054 6 1.60, 0.059 6 0.87, 0.194 6 0.85) showed no difference compared with placebo (-0.037 6 0.68, 0.030 6 0.22, -0.059 6 0.56, 0.088 6 1.17). Out of the total AEs and SAEs during the induction period, one patient in single group and 3 in early group had cardiac AEs, and 2 in the early group had cardiac SAEs. During the maintenance period, 5 cardiac AEs and 1 cardiac SAE were reported in the open label group. No death was reported in this study. Conclusion: These findings indicate that secukinumab treatment appeared not to be associated with any change in the lipid profile (TC, HDLc, LDLc, and TG) of patients with moderate to severe plaque psoriasis.
Methods: Patients with active moderate to severe plaque-type psoriasis and healthy volunteers were included. Serum concentrations of CXCL9, CXCL10 and CXCL16, in addition to TNF-a, were measured by ELISA assay. Because of low plasma levels, some tests were run on supernatant from peripheral blood mononuclear cells cultures stimulated with LPS for 48 hours. Results: We evaluated 26 patients with psoriasis and 12 controls. Psoriatic patients had mean PASI of 13.7 and mean BSA of 29.5%. Age was similar in both groups, with mean (SD) of 54.3 (9.4) and 50.6 (6.7) years old in the psoriasis and control group, respectively. Fourteen patients with psoriasis (53.8%) had arthritis. Two patients were on systemic therapies for psoriasis (methotrexate and acitretin). There were no differences between serum levels of CXCL9 and CXCL10 in psoriatic patients and controls (P ¼ 0.44 and 0.77, respectively). Interestingly, among patients with psoriasis, levels of these chemokines were lower in patients with arthritis (CXCL9, P \ .05 and CXCL10, P ¼.14). Expectedly, serum levels of TNF-a were higher in the psoriasis group (P\.05) and levels of CXCL16 were similar in both groups (P ¼.66). Furthermore, levels of the chemokines evaluated were not correlated with disease severity. Conclusion: Serum levels of the CXCL9, CXCL10, and CXCL16 in patients with moderate to severe psoriasis were not significantly different from controls, despite active and incompletely treated disease. Although our study had a small sample size, we were able to confirm higher levels of TNF-a in patients with psoriasis. Commercial support: None identified.
This study was sponsored by Novartis Pharma AG, Basel, Switzerland.
P6343 Serious infection events in the psoriasis longitudinal assessment and registry (PSOLAR) study: Current status of observations Craig Leonardi, MD, St. Louis University, St. Louis, MO, United States; David Fiorentino, MD, PhD, Stanford University, Stanford, CA, United States; Marc Chevrier, MD, Janssen Services, LLC, Horsham, PA, United States; Robert Kalb, MD, SUNY at Buffalo, Buffalo, NY, United States Objective: To report serious infection (SI) events observed in PSOLAR, evaluating long-term safety andclinical outcomes for pts receiving (or eligible to receive) tx for PsO with biologics and/or conventional systemic agents in practices. Methods: PSOLAR captures events following exposure to systemic therapies. Safety observations captured for ustekinumab and infliximab-exposed pts support sponsor regulatory commitments. Prevalence and incidence of SI in moderate to severe PsO populations using systemic immunomodulatory therapies are evaluated.The accrual of all SI by exposure subgroups, through August 23, 2011, are summarized. Results: 9495 pts enrolled (13,733 cumulative pt-yrs). Unadjusted rates of SI, based on any exposure, varied across exposure groups (in order of event attribution): ustekinumab 0.60 events/100 pt yrs of observation (PYO) [14 events/2332 PYO], anti-TNF sponsor biologics (infliximab, golimumab) 3.06/100 PYO [66/2158], nonsponsor biologics (almost exclusively etanercept/adalimumab) 1.32/100 PYO [85/6458], nonbiologics 0.97/100 PYO [27/2784], and overall 1.40 [192/13733]. (Exposure definition: event counts add to the exposure group that has the highest position in the order of attribution, before/at time ofAE.) 57% of ustekinumab pts were exposed at/after entry into PSOLAR; ustekinumab cohort represents a balance of new andprior/ongoing exposure to sample infection rates over varying levels of exposure. To better compare rates observed in pts with different exposure patterns, more infections events than currently available would be needed for rigorous, comparative statistical analyses. Limitations: Because of channeling of therapy, differences in subgroup characteristics exist (eg. more pts aged [65 yrs not exposed to biologics, could influence rate of SI, given the increased prevalence of infection in the elderly). Potential confounding considerations include arthritis and obesity, which tend to cluster with some product exposures. Any formal comparison will require statistical modeling to adjust for pt characteristics andrisks, including consideration of multiple treatments.
P5957 Study of enhanced ferritin/iron ratio in psoriasis K. H. Basavaraj, MBBS, MD, JSS Medical College, JSS University, Mysore, India; R. Rashmi, MMSc, JSS Medical College, JSS University, Mysore, India Background: Psoriasis is a chronic and recurrent skin disorder. The pathogenesis of this complex, multifactorial disease is incompletely understood. The involvement of trace metals and metal binding proteins has been studied and reported. Limited data are available elucidating the roles of iron and iron-binding proteins in psoriasis. However, studies reporting the changes in iron and iron binding proteins with psoriasis severity are scarce.
Conclusion: These are preliminary observations, and PSOLAR will follow pts for up to 8 yrs, providing more robust results. Although the numbers of SI are modest, initial rates help to define activity in a population without significant inclusion/exclusion criteria. PSOLAR represents a powerful resource for tracking population safety events of interest, among pts eligible to receive systemic therapies.
Observation: Serum ferritin was analyzed in 81 patients with psoriasis and 45 healthy control subjects. The patients were grouped as mild, moderate, and severe based on Psoriasis Area Severity Index (PASI). The ferritin values in psoriasis patients were not significantly different (P [.05) from that of controls. Further, there was no significant difference (P[.05) in ferritin concentrations between groups of severity. Serum iron (Fe) was also estimated in both psoriasis and control samples. Fe was found to be significantly reduced (P \.05) in the psoriasis patients when compared to controls, though there was no significant difference (P [ .05) seen between groups of severity. The ferritin to Fe ratio was significantly higher (P \.05) in the psoriasis groups when compared to the control group. Conclusion: Our results suggest a possible role of ferritin in psoriasis. This study also directs observations indicating a possibility of using ferritin to Fe ratio as a probable marker for the disease.
Supported by Janssen Services, LLC.
Commercial support: None identified.
APRIL 2013
J AM ACAD DERMATOL
AB213
P6554
Secukinumab treatment shows a neutral impact on the lipid profile of patients with moderate to severe plaque psoriasis in a dose-ranging study Sandra Philipp, Charite-Universit€atsmedizin Berlin, Berlin, Germany; Cesar Escrig, Novartis Pharma AG, Basel, Switzerland; Charis Papavassilis, Novartis Pharma AG, Basel, Switzerland; Diamant Thac¸i, Goethe-University, Frankfurt, Germany; Helen Thurston, Novartis Pharma AG, Basel, Switzerland
Serum chemokine profile in psoriasis Xinaida Lima, MD, MPH, State University of Campinas - UNICAMP, Campinas - S~ao Paulo, Brazil; Fernanda Braga, MS, State University of Campinas - UNICAMP, Campinas - S~ao Paulo, Brazil; Maria Heloisa Blotta, PhD, State University of Campinas - UNICAMP, Campinas - S~ao Paulo, Brazil; Renata Magalh~aes, MD, PhD, State University of Campinas - UNICAMP, Campinas - S~ao Paulo, Brazil; Ronei Mamoni, PhD, State University of Campinas - UNICAMP, Campinas - S~ao Paulo, Brazil Background: The chemokines CXCL9 and CXCL10 interact with receptor CXCR3; and CXCL16 binds to CXCR6. These receptors are implicated in skin homing. Previous studies have shown increased serum levels of CXCL9 and CXCL10 in autoimmune disorders, including psoriatic arthritis (CXCL10). A recent study showed upregulation of CXCL16 in psoriatic lesional skin, but not in the serum. The aim of our study was to evaluate these chemokine ligands in psoriasis.
Background: Psoriasis is a chronic, immune-mediated skin disorder associated with increased levels of interleukin (IL)-17A. Secukinumab, a fully human antieIL-17A monoclonal antibody, has shown therapeutic potential in treatment of plaque psoriasis. In this phase II, double-blind, placebo-controlled trial, we report the effect of secukinumab on the lipid profile of patients with moderate to severe plaque psoriasis. Methods: Patients (N ¼ 404) were randomized (1:2:2:1) to either placebo (n ¼ 67) or one of the 3 subcutaneous secukinumab 150-mg regimens: single (week 0; n ¼ 66), early (weeks 0, 1, 2, 4; n ¼ 133), and monthly (weeks 0, 4, 8; n ¼ 138). Following a 12-week induction period, PASI 75 responders were further randomized (1:1) to 2 maintenance regimens for 20 weeks: the fixed-interval regimen (n ¼ 65; secukinumab 150 mg at weeks 12 and 24) or the treatment at start-of-relapse regimen (n ¼ 67; secukinumab 150 mg during visits at which start of relapse was observed). Nonresponders (not achieving PASI 50), partial responders (achieving PASI 50 but not PASI 75), and patients with 2 consecutive relapses entered the open label phase (secukinumab 150 mg every 4 weeks up to week 32). Patients were followed up for 12 weeks after the last dose. Results: Baseline disease characteristics were comparable between treatment groups. Secukinumab had a neutral effect on the lipid profile of patients compared with placebo and this was maintained throughout the study period. Mean change 6 SD (mmol/L) from baseline to last visit in the induction period or follow-up period for secukinumab single, monthly, early regimens in TC (-0.004 6 0.69, 0.102 6 0.64, 0.122 6 0.73), HDLc (0.012 6 0.19, 0.005 6 0.17, 0.005 6 0.23), LDLc (-0.020 6 0.52, 0.066 6 0.54, 0.025 6 0.65), and TG (0.054 6 1.60, 0.059 6 0.87, 0.194 6 0.85) showed no difference compared with placebo (-0.037 6 0.68, 0.030 6 0.22, -0.059 6 0.56, 0.088 6 1.17). Out of the total AEs and SAEs during the induction period, one patient in single group and 3 in early group had cardiac AEs, and 2 in the early group had cardiac SAEs. During the maintenance period, 5 cardiac AEs and 1 cardiac SAE were reported in the open label group. No death was reported in this study. Conclusion: These findings indicate that secukinumab treatment appeared not to be associated with any change in the lipid profile (TC, HDLc, LDLc, and TG) of patients with moderate to severe plaque psoriasis.
Methods: Patients with active moderate to severe plaque-type psoriasis and healthy volunteers were included. Serum concentrations of CXCL9, CXCL10 and CXCL16, in addition to TNF-a, were measured by ELISA assay. Because of low plasma levels, some tests were run on supernatant from peripheral blood mononuclear cells cultures stimulated with LPS for 48 hours. Results: We evaluated 26 patients with psoriasis and 12 controls. Psoriatic patients had mean PASI of 13.7 and mean BSA of 29.5%. Age was similar in both groups, with mean (SD) of 54.3 (9.4) and 50.6 (6.7) years old in the psoriasis and control group, respectively. Fourteen patients with psoriasis (53.8%) had arthritis. Two patients were on systemic therapies for psoriasis (methotrexate and acitretin). There were no differences between serum levels of CXCL9 and CXCL10 in psoriatic patients and controls (P ¼ 0.44 and 0.77, respectively). Interestingly, among patients with psoriasis, levels of these chemokines were lower in patients with arthritis (CXCL9, P \ .05 and CXCL10, P ¼.14). Expectedly, serum levels of TNF-a were higher in the psoriasis group (P\.05) and levels of CXCL16 were similar in both groups (P ¼.66). Furthermore, levels of the chemokines evaluated were not correlated with disease severity. Conclusion: Serum levels of the CXCL9, CXCL10, and CXCL16 in patients with moderate to severe psoriasis were not significantly different from controls, despite active and incompletely treated disease. Although our study had a small sample size, we were able to confirm higher levels of TNF-a in patients with psoriasis. Commercial support: None identified.
This study was sponsored by Novartis Pharma AG, Basel, Switzerland.
P6343 Serious infection events in the psoriasis longitudinal assessment and registry (PSOLAR) study: Current status of observations Craig Leonardi, MD, St. Louis University, St. Louis, MO, United States; David Fiorentino, MD, PhD, Stanford University, Stanford, CA, United States; Marc Chevrier, MD, Janssen Services, LLC, Horsham, PA, United States; Robert Kalb, MD, SUNY at Buffalo, Buffalo, NY, United States Objective: To report serious infection (SI) events observed in PSOLAR, evaluating long-term safety andclinical outcomes for pts receiving (or eligible to receive) tx for PsO with biologics and/or conventional systemic agents in practices. Methods: PSOLAR captures events following exposure to systemic therapies. Safety observations captured for ustekinumab and infliximab-exposed pts support sponsor regulatory commitments. Prevalence and incidence of SI in moderate to severe PsO populations using systemic immunomodulatory therapies are evaluated.The accrual of all SI by exposure subgroups, through August 23, 2011, are summarized. Results: 9495 pts enrolled (13,733 cumulative pt-yrs). Unadjusted rates of SI, based on any exposure, varied across exposure groups (in order of event attribution): ustekinumab 0.60 events/100 pt yrs of observation (PYO) [14 events/2332 PYO], anti-TNF sponsor biologics (infliximab, golimumab) 3.06/100 PYO [66/2158], nonsponsor biologics (almost exclusively etanercept/adalimumab) 1.32/100 PYO [85/6458], nonbiologics 0.97/100 PYO [27/2784], and overall 1.40 [192/13733]. (Exposure definition: event counts add to the exposure group that has the highest position in the order of attribution, before/at time ofAE.) 57% of ustekinumab pts were exposed at/after entry into PSOLAR; ustekinumab cohort represents a balance of new andprior/ongoing exposure to sample infection rates over varying levels of exposure. To better compare rates observed in pts with different exposure patterns, more infections events than currently available would be needed for rigorous, comparative statistical analyses. Limitations: Because of channeling of therapy, differences in subgroup characteristics exist (eg. more pts aged [65 yrs not exposed to biologics, could influence rate of SI, given the increased prevalence of infection in the elderly). Potential confounding considerations include arthritis and obesity, which tend to cluster with some product exposures. Any formal comparison will require statistical modeling to adjust for pt characteristics andrisks, including consideration of multiple treatments.
P5957 Study of enhanced ferritin/iron ratio in psoriasis K. H. Basavaraj, MBBS, MD, JSS Medical College, JSS University, Mysore, India; R. Rashmi, MMSc, JSS Medical College, JSS University, Mysore, India Background: Psoriasis is a chronic and recurrent skin disorder. The pathogenesis of this complex, multifactorial disease is incompletely understood. The involvement of trace metals and metal binding proteins has been studied and reported. Limited data are available elucidating the roles of iron and iron-binding proteins in psoriasis. However, studies reporting the changes in iron and iron binding proteins with psoriasis severity are scarce.
Conclusion: These are preliminary observations, and PSOLAR will follow pts for up to 8 yrs, providing more robust results. Although the numbers of SI are modest, initial rates help to define activity in a population without significant inclusion/exclusion criteria. PSOLAR represents a powerful resource for tracking population safety events of interest, among pts eligible to receive systemic therapies.
Observation: Serum ferritin was analyzed in 81 patients with psoriasis and 45 healthy control subjects. The patients were grouped as mild, moderate, and severe based on Psoriasis Area Severity Index (PASI). The ferritin values in psoriasis patients were not significantly different (P [.05) from that of controls. Further, there was no significant difference (P[.05) in ferritin concentrations between groups of severity. Serum iron (Fe) was also estimated in both psoriasis and control samples. Fe was found to be significantly reduced (P \.05) in the psoriasis patients when compared to controls, though there was no significant difference (P [ .05) seen between groups of severity. The ferritin to Fe ratio was significantly higher (P \.05) in the psoriasis groups when compared to the control group. Conclusion: Our results suggest a possible role of ferritin in psoriasis. This study also directs observations indicating a possibility of using ferritin to Fe ratio as a probable marker for the disease.
Supported by Janssen Services, LLC.
Commercial support: None identified.
APRIL 2013
J AM ACAD DERMATOL
AB213