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Adalimumab is effective for psoriasis patients who are primary nonresponders to etanercept: Subanalysis of an open-label clinical trial
Molecular determination of mixed infections of dermatophytes and nondermatophyte molds in onychomycosis patients undergoing therapy
Cardiovascular disease in psoriasis: Survey results from primary care physicians and cardiologists
Aditya Gupta, MD, PhD, Division of Dermatology, Department of Medicine, Toronto, Canada; Kerry-Ann Nakrieko, PhD, Mycology Division, Mediprobe Research Inc, London, Canada
Kory Parsi, University of California, Davis, Sacramento, CA, United States; April Armstrong, MD, MPH, University of California Davis, Sacramento, CA, United States; Chin-Shang Li, PhD, University of California Davis, Sacramento, CA, United States; Elizabeth Brezinski, , University of California, Davis, Sacramento, CA, United States; Tzu-Chun Lin, University of California Davis, Sacramento, CA, United States
(Poster reference number 5610)
Background: Nondermatophyte molds (NDMs) account for approximately 10% of onychomycosis with the majority of cases caused by dermatophytes and yeasts. Due to the relatively rarity of this type of onychomycosis, data reporting clinical presentations, epidemiology, and best treatment strategies are limited. Even more limited is the occurrence of mixed onychomycosis infections of dermatophytes and NDMs. This is likely due to the use of the NDM inhibitor, cycloheximide, in the isolation of dermatophytes which results in a misrepresentation of mixed infection prevalence. Methods: This study focuses on mixed infections of the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes with the following NDMs: Acremonium spp., Aspergillus spp., Fusarium oxysporum, Scopulariopsis brevicaulis, and Scytalidium spp. To avoid the complications involved in the culture isolation of NDMs, a molecular approach was used to identify the occurrence of mixed infections directly from nail samples using polymerase chain reaction (PCR)-restriction fragment length polymorphism analyses and nested PCR. Two or three serial samples were taken to ensure accuracy. North American onychomycosis patients (n ¼ 45), undergoing antifungal treatment were included in this study. Results: T rubrum/NDM mixed infections were found in 32% of samples with each NDM at the following rates: Acremonium spp,. 4%; Aspergillus spp., 2%; F oxysporum, 13%; S brevicaulis, 9%; and Scytalidium spp., 4%. Samples mixed with T rubrum and two NDM were present at a rate of 6%. T mentagrophytes/NDM mixed infections were present in 4% of samples analyzed with the NDM at the following rates: Aspergillus spp., 2%; and F oxysporum, 2%. Conclusion: This method provides a faster, more accurate measure of the assessment of mixed infections in onychomycosis and allows important questions regarding epidemiology and treatment to be addressed. Both T rubrum and T mentagrophytes infections are more prone to be mixed with F oxysporum. T rubrum infections are also more susceptible to be mixed with S brevicaulis. These findings provide valuable insight into mixed infections susceptibility or resistance to antifungal treatments and may help to profile patients at risk for reinfection after an ‘‘apparent’’ mycological cure. These data are the first North American report to determine the frequency of mixed infections in onychomycosis patients. Commercial support: None identified.
(Poster reference number 4928)
Background: Current evidence suggests a higher prevalence of cardiovascular (CV) risk factors and events in psoriasis patients. The National Psoriasis Foundation guidelines recommend screening for CV risk factors starting at age 20. However, the current state of screening practices for CV risk factors by cardiologists and primary care physicians (PCPs) is unknown. Objective: We aimed to assess awareness among cardiologists and PCPs of the potentially increased risk of CV events in psoriasis patients and to identify physician practice patterns of screening for CV risk factors in psoriasis patients. Methods: We distributed surveys to cardiologists and PCPs between October 1, 2010 and April 15, 2011. Physicians were randomly selected through professional society registries, which included the American College of Cardiology and the American Academy of Family Physicians. Univariable and multivariable logistic regression and two-sided McNemar’s tests were used to compare results. Results: We received 60 (24%) responses from cardiologists and 191 (76%) responses from PCPs. Overall, 45% (113/251) of all physicians were aware that psoriasis was associated with an increased risk of CV events. Approximately 43% (108/251) of physicians reported screening psoriasis patients starting at age 20 for hypertension; 11% (27/251) reported screening for coronary artery disease, and 30% (75/251) reported screening for obesity. Cardiologists were 1.85 times more likely to be aware of an increased risk of CV events among psoriasis patients than PCPs (P ¼ .039; 95% CI, 1.032-3.332). Compared to their awareness of CV comorbidities associated with psoriasis, both cardiologists and PCPs were significantly more aware of increased CV comorbidities associated with rheumatoid arthritis (P \.0001) and systemic lupus erythematosus (P \.0001). Conclusions: Fewer than half of surveyed cardiologists and PCPs screen psoriasis patients for CV risk factors. Cardiologists were more likely than PCPs to be cognizant of CV comorbidities in psoriasis patients. Both cardiologists and PCPs were less aware of CV comorbidities associated with psoriasis compared to those associated with rheumatoid arthritis and systemic lupus erythematosus. Commercial support: None identified.
Adalimumab is effective for psoriasis patients who are primary nonresponders to etanercept: Subanalysis of an open-label clinical trial
(Poster reference number 4767)
Bruce Strober, University of Connecticut School of Medicine, Farmington, CT, United States; Jamie Weisman, Peachtree Dermatology Associates Research Center, Atlanta, GA, United States; Martin Okun, Abbott Laboratories, Abbott Park, IL, United States; Yihua Gu, Abbott Laboratories, Abbott Park, IL, United States Objective: To assess adalimumab efficacy in psoriasis patients who were primary nonresponders or secondary nonresponders to etanercept (ETN), methotrexate (MTX), or narrow-band ultraviolet B phototherapy (UVB; NCT00566722 Methods: This 16-week, multicenter, open-label trial enrolled psoriasis patients who were adalimumab-na€ıve and who had suboptimal response to ETN, MTX, or UVB. Adalimumab was dosed 40 mg every other week from weeks 1 to 15, following an initial dose of 80 mg at week 0. The proportion of patients achieving clinical response, defined as a Physician’s Global Assessment of ‘clear’ or ‘minimal’ at week 16 was analyzed in the intent-to-treat population with nonresponder imputation for missing data. Results were analyzed overall and for the subgroups of primary nonresponders (NR) (never achieved satisfactory response to the prior therapy) and secondary nonresponders (achieved satisfactory response initially but lost it over time). Patients who reported both ‘‘never achieved satisfactory response’’ and ‘‘achieved satisfactory response initially but lost it over time’’ were included in both subgroups; patients who discontinued their prior therapies due to reasons other than efficacy were not included in the above subgroup summaries. Results: Of 152 patients enrolled, the number of patients on each prior treatment was: ETN, N ¼ 82; MTX, N ¼ 41; and UVB, N ¼ 29. The percentages of primary NRs/secondary NRs by prior treatment were: ETN 31.7%/70.7%, MTX 65.9%/29.3%, and UVB 62.1%/37.9%. At week 16, the overall response rate to adalimumab was 52.0%; 60.6% of Primary NRs and 44.4% of Secondary NRs achieved clinical response. Among patients with prior ETN treatment, clinical response was achieved by 57.7%/46.6% of the primary NRs/secondary NRs; among patients with prior MTX therapy, clinical response was achieved by 63.0%/50.0% of the primary NRs/secondary NRs; among patients with prior UVB therapy, clinical response was achieved by 61.1%/27.3% of the primary NRs/secondary NRs. Conclusion: Adalimumab treatment led to clinical response in the majority of patients who had been suboptimally controlled on etanercept, methotrexate, or narrow-band ultraviolet B phototherapy. The majority of patients who had never achieved satisfactory response with etanercept were able to achieve clinical response after switching to adalimumab. Commercial support: 100% sponsored by Abbott Laboratories.
AB8
J AM ACAD DERMATOL
Is psoriasis an independent risk factor for ischemic heart disease (IHD)?
(Poster reference number 5522)
Marian McEvoy, MBBCh, Mayo Clinic, Rochester, MN, United States; Bharath Manu Akkara Veetil, MBChB, Mayo Clinic, Richester, MN, United States; Cynthia Crowson, MS, Mayo Clinic, Rochester, MN, United States; Eric Matteson, MD, PharmD, Mayo Clinic, Rochester, MN, United States; Hilal Maradit-Kremers, MD, Mayo Clinic, Rochester, MN, United States Previous studies have shown that cardiac mortality is increased in patients with psoriasis. It is unknown whether psoriasis acts through conventional IHD risk factors or is a new independent risk factor. We performed a population based study to evaluate the validity of the Framingham Risk Score, a validated measure of standard IHD risk factors, in predicting the incidence of ischemic heart disease in patients with psoriasis. This tested the hypothesis that psoriasis is not an independent cardiac risk factor. We compared the risk of cardiac death/myocardial infarction based on the FRS with the actual incidence of myocardial infarction/ cardiac death in the study population. Statistical analysis included Poisson regression models and standardized incidence ratios (SIRs). The study population consisted of 1309 psoriatics [30 years old without a prior myocardial infarct. Full Framingham risk factors were available in 74% of this psoriasis population. Cardiac disease occurred at the same rate in psoriasis patients with (74%) and without FRS (26%) (log rank P ¼.07). The median FRS score was 3.8%, with an observed 10 year risk of coronary heart disease was 5.5%. The SIR between the two groups, observed versus predicted, was 0.90. SIR analysis showed no difference when analyzed for gender or age [65, \65 years. The Framingham risk score is a valid tool when used to predict risk of cardiac events in patients with psoriasis, thus supporting the hypothesis that psoriasis is not an independent cardiac risk factor. Commercial support: This work was partially funded by a grant from Pfizer and was made possible by a grant from Amgen/Wyeth and by the Rochester Epidemiology Project (R01 AG034676 from the National Institute on Aging).
APRIL 2012
Cardiovascular disease in psoriasis: Survey results from primary care physicians and cardiologists
Aditya Gupta, MD, PhD, Division of Dermatology, Department of Medicine, Toronto, Canada; Kerry-Ann Nakrieko, PhD, Mycology Division, Mediprobe Research Inc, London, Canada
Kory Parsi, University of California, Davis, Sacramento, CA, United States; April Armstrong, MD, MPH, University of California Davis, Sacramento, CA, United States; Chin-Shang Li, PhD, University of California Davis, Sacramento, CA, United States; Elizabeth Brezinski, , University of California, Davis, Sacramento, CA, United States; Tzu-Chun Lin, University of California Davis, Sacramento, CA, United States
(Poster reference number 5610)
Background: Nondermatophyte molds (NDMs) account for approximately 10% of onychomycosis with the majority of cases caused by dermatophytes and yeasts. Due to the relatively rarity of this type of onychomycosis, data reporting clinical presentations, epidemiology, and best treatment strategies are limited. Even more limited is the occurrence of mixed onychomycosis infections of dermatophytes and NDMs. This is likely due to the use of the NDM inhibitor, cycloheximide, in the isolation of dermatophytes which results in a misrepresentation of mixed infection prevalence. Methods: This study focuses on mixed infections of the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes with the following NDMs: Acremonium spp., Aspergillus spp., Fusarium oxysporum, Scopulariopsis brevicaulis, and Scytalidium spp. To avoid the complications involved in the culture isolation of NDMs, a molecular approach was used to identify the occurrence of mixed infections directly from nail samples using polymerase chain reaction (PCR)-restriction fragment length polymorphism analyses and nested PCR. Two or three serial samples were taken to ensure accuracy. North American onychomycosis patients (n ¼ 45), undergoing antifungal treatment were included in this study. Results: T rubrum/NDM mixed infections were found in 32% of samples with each NDM at the following rates: Acremonium spp,. 4%; Aspergillus spp., 2%; F oxysporum, 13%; S brevicaulis, 9%; and Scytalidium spp., 4%. Samples mixed with T rubrum and two NDM were present at a rate of 6%. T mentagrophytes/NDM mixed infections were present in 4% of samples analyzed with the NDM at the following rates: Aspergillus spp., 2%; and F oxysporum, 2%. Conclusion: This method provides a faster, more accurate measure of the assessment of mixed infections in onychomycosis and allows important questions regarding epidemiology and treatment to be addressed. Both T rubrum and T mentagrophytes infections are more prone to be mixed with F oxysporum. T rubrum infections are also more susceptible to be mixed with S brevicaulis. These findings provide valuable insight into mixed infections susceptibility or resistance to antifungal treatments and may help to profile patients at risk for reinfection after an ‘‘apparent’’ mycological cure. These data are the first North American report to determine the frequency of mixed infections in onychomycosis patients. Commercial support: None identified.
(Poster reference number 4928)
Background: Current evidence suggests a higher prevalence of cardiovascular (CV) risk factors and events in psoriasis patients. The National Psoriasis Foundation guidelines recommend screening for CV risk factors starting at age 20. However, the current state of screening practices for CV risk factors by cardiologists and primary care physicians (PCPs) is unknown. Objective: We aimed to assess awareness among cardiologists and PCPs of the potentially increased risk of CV events in psoriasis patients and to identify physician practice patterns of screening for CV risk factors in psoriasis patients. Methods: We distributed surveys to cardiologists and PCPs between October 1, 2010 and April 15, 2011. Physicians were randomly selected through professional society registries, which included the American College of Cardiology and the American Academy of Family Physicians. Univariable and multivariable logistic regression and two-sided McNemar’s tests were used to compare results. Results: We received 60 (24%) responses from cardiologists and 191 (76%) responses from PCPs. Overall, 45% (113/251) of all physicians were aware that psoriasis was associated with an increased risk of CV events. Approximately 43% (108/251) of physicians reported screening psoriasis patients starting at age 20 for hypertension; 11% (27/251) reported screening for coronary artery disease, and 30% (75/251) reported screening for obesity. Cardiologists were 1.85 times more likely to be aware of an increased risk of CV events among psoriasis patients than PCPs (P ¼ .039; 95% CI, 1.032-3.332). Compared to their awareness of CV comorbidities associated with psoriasis, both cardiologists and PCPs were significantly more aware of increased CV comorbidities associated with rheumatoid arthritis (P \.0001) and systemic lupus erythematosus (P \.0001). Conclusions: Fewer than half of surveyed cardiologists and PCPs screen psoriasis patients for CV risk factors. Cardiologists were more likely than PCPs to be cognizant of CV comorbidities in psoriasis patients. Both cardiologists and PCPs were less aware of CV comorbidities associated with psoriasis compared to those associated with rheumatoid arthritis and systemic lupus erythematosus. Commercial support: None identified.
Adalimumab is effective for psoriasis patients who are primary nonresponders to etanercept: Subanalysis of an open-label clinical trial
(Poster reference number 4767)
Bruce Strober, University of Connecticut School of Medicine, Farmington, CT, United States; Jamie Weisman, Peachtree Dermatology Associates Research Center, Atlanta, GA, United States; Martin Okun, Abbott Laboratories, Abbott Park, IL, United States; Yihua Gu, Abbott Laboratories, Abbott Park, IL, United States Objective: To assess adalimumab efficacy in psoriasis patients who were primary nonresponders or secondary nonresponders to etanercept (ETN), methotrexate (MTX), or narrow-band ultraviolet B phototherapy (UVB; NCT00566722 Methods: This 16-week, multicenter, open-label trial enrolled psoriasis patients who were adalimumab-na€ıve and who had suboptimal response to ETN, MTX, or UVB. Adalimumab was dosed 40 mg every other week from weeks 1 to 15, following an initial dose of 80 mg at week 0. The proportion of patients achieving clinical response, defined as a Physician’s Global Assessment of ‘clear’ or ‘minimal’ at week 16 was analyzed in the intent-to-treat population with nonresponder imputation for missing data. Results were analyzed overall and for the subgroups of primary nonresponders (NR) (never achieved satisfactory response to the prior therapy) and secondary nonresponders (achieved satisfactory response initially but lost it over time). Patients who reported both ‘‘never achieved satisfactory response’’ and ‘‘achieved satisfactory response initially but lost it over time’’ were included in both subgroups; patients who discontinued their prior therapies due to reasons other than efficacy were not included in the above subgroup summaries. Results: Of 152 patients enrolled, the number of patients on each prior treatment was: ETN, N ¼ 82; MTX, N ¼ 41; and UVB, N ¼ 29. The percentages of primary NRs/secondary NRs by prior treatment were: ETN 31.7%/70.7%, MTX 65.9%/29.3%, and UVB 62.1%/37.9%. At week 16, the overall response rate to adalimumab was 52.0%; 60.6% of Primary NRs and 44.4% of Secondary NRs achieved clinical response. Among patients with prior ETN treatment, clinical response was achieved by 57.7%/46.6% of the primary NRs/secondary NRs; among patients with prior MTX therapy, clinical response was achieved by 63.0%/50.0% of the primary NRs/secondary NRs; among patients with prior UVB therapy, clinical response was achieved by 61.1%/27.3% of the primary NRs/secondary NRs. Conclusion: Adalimumab treatment led to clinical response in the majority of patients who had been suboptimally controlled on etanercept, methotrexate, or narrow-band ultraviolet B phototherapy. The majority of patients who had never achieved satisfactory response with etanercept were able to achieve clinical response after switching to adalimumab. Commercial support: 100% sponsored by Abbott Laboratories.
AB8
J AM ACAD DERMATOL
Is psoriasis an independent risk factor for ischemic heart disease (IHD)?
(Poster reference number 5522)
Marian McEvoy, MBBCh, Mayo Clinic, Rochester, MN, United States; Bharath Manu Akkara Veetil, MBChB, Mayo Clinic, Richester, MN, United States; Cynthia Crowson, MS, Mayo Clinic, Rochester, MN, United States; Eric Matteson, MD, PharmD, Mayo Clinic, Rochester, MN, United States; Hilal Maradit-Kremers, MD, Mayo Clinic, Rochester, MN, United States Previous studies have shown that cardiac mortality is increased in patients with psoriasis. It is unknown whether psoriasis acts through conventional IHD risk factors or is a new independent risk factor. We performed a population based study to evaluate the validity of the Framingham Risk Score, a validated measure of standard IHD risk factors, in predicting the incidence of ischemic heart disease in patients with psoriasis. This tested the hypothesis that psoriasis is not an independent cardiac risk factor. We compared the risk of cardiac death/myocardial infarction based on the FRS with the actual incidence of myocardial infarction/ cardiac death in the study population. Statistical analysis included Poisson regression models and standardized incidence ratios (SIRs). The study population consisted of 1309 psoriatics [30 years old without a prior myocardial infarct. Full Framingham risk factors were available in 74% of this psoriasis population. Cardiac disease occurred at the same rate in psoriasis patients with (74%) and without FRS (26%) (log rank P ¼.07). The median FRS score was 3.8%, with an observed 10 year risk of coronary heart disease was 5.5%. The SIR between the two groups, observed versus predicted, was 0.90. SIR analysis showed no difference when analyzed for gender or age [65, \65 years. The Framingham risk score is a valid tool when used to predict risk of cardiac events in patients with psoriasis, thus supporting the hypothesis that psoriasis is not an independent cardiac risk factor. Commercial support: This work was partially funded by a grant from Pfizer and was made possible by a grant from Amgen/Wyeth and by the Rochester Epidemiology Project (R01 AG034676 from the National Institute on Aging).
APRIL 2012