Psoriasis linked to diabetes, hypertension: study

CHICAGO, 22 april 2009 - Women with psoriasis run a higher risk of diabetes and high blood pressure, perhaps because of the underlying inflammation that causes the skin condition, researchers said on Monday.

Psoriasis should be considered "a systemic disorder, rather than simply a skin disease," Dr. Abrar Qureshi of Brigham and Women's Hospital and Harvard Medical School in Boston wrote in a study in the April issue of Archives of Dermatology.

They looked at data from thousands of female U.S. nurses who enrolled in a study in 1991 and have been checked periodically for numerous health-related issues.

They said 1,813 women were diagnosed with psoriasis over a 14-year period. These women were 63 percent more likely to develop diabetes and 17 percent more likely to develop hypertension than those who were psoriasis-free.

The team said inflammation can lead to high blood pressure and may also be a factor in insulin resistance, a pre-diabetic condition.

"Inflammation could be a biologically plausible mechanism" underlying the association with diabetes, the researchers said. "Psoriasis is a chronic inflammatory disease, and inflammation is a risk factor for hypertension."

The link was found regardless of their weight, age and whether they smoked. While other studies have linked psoriasis to diabetes and hypertension, factors like obesity and smoking have variously been blamed, the researchers said.

Psoriasis, a chronic inflammatory skin disease that causes itchy red plaques on the skin's surface, affects about 7.5 million people in the United States alone. In severe cases large areas of the body can be affected, and it can bring arthritis, depression and other problems.

Because the study was restricted to white women, the findings cannot be generalized to men or to other races, the researchers added.

While systemic steroid therapy for psoriasis could foster diabetes or hypertension, such treatment is not the standard for care in the United States, the researchers said. And patients often abandon steroid creams after short periods of use.

Severe, But Not Mild, Psoriasis May Increase Mortality by 50%

Laurie Barclay
December 20, 2007 — Patients with severe psoriasis had a 50% increased risk for mortality, but those with mild psoriasis had no overall increase in risk, according to the results of a population-based cohort study reported in the December issue of the Archives of Dermatology.
"Few studies have assessed the risk of mortality in patients with psoriasis, and most have focused on patients hospitalized for treatment," write Joel M. Gelfand, MD, MSCE, from the University of Pennsylvania School of Medicine in Philadelphia, and colleagues. "Presently, there are mixed data regarding the risk of mortality among patients with severe psoriasis, and the available data suggest a hypothesis that the risk of mortality may be related to disease severity. To further investigate the relationship of psoriasis and mortality, we performed a population-based cohort study in the United Kingdom to determine the risk of mortality in patients with psoriasis."
In this cohort study, patients and control subjects were identified from the practices of general practitioners participating in the General Practice Research Database in the United Kingdom from 1987 to 2002. Mild psoriasis was defined as a diagnostic code of psoriasis but no history of systemic therapy, whereas severe psoriasis was defined as a diagnostic code of psoriasis and a history of systemic therapy consistent with severe psoriasis. Control patients, with no history of a psoriasis diagnostic code, were selected in a 5:1 ratio from the same practice and date as the patients with psoriasis. The primary endpoint was hazard ratio (HR) of time to death with use of Cox proportional hazards models, after adjustment for age and sex.
Mild psoriasis had no overall effect on mortality (HR, 1.0; 95% confidence interval [CI], 0.97 - 1.02). In contrast, overall mortality risk was increased in patients with severe psoriasis (HR, 1.5; 95% CI, 1.3 - 1.7). Adjustment for other risk factors for mortality did not significantly affect the association of severe psoriasis with mortality (HR, 1.4; 95% CI, 1.3 - 1.6), nor did exclusion of patients with inflammatory arthropathy (HR, 1.5; 95% CI, 1.3 - 1.8).
Compared with control patients, male and female patients with severe psoriasis died 3.5 years younger (95% CI, 1.2 - 5.8) and 4.4 years younger (95% CI, 2.2 - 6.6), respectively (P < .001).
"Patients with severe psoriasis have a 50% increased risk of mortality, whereas patients with milder psoriasis have no overall increased risk," the study authors write.
Limitations of the study include possible misclassification of death from coding errors, failure to examine patients with exclusively incident (new-onset) psoriasis, possible misclassification of mild and severe psoriasis based on therapy, and inability to determine why patients with severe psoriasis died at higher rates than patients without psoriasis.
"Patients treated for severe psoriasis have an increased risk of death and die at a younger age than patients without psoriasis," the study authors conclude. "Further studies are necessary to determine the cause of excess mortality in patients with severe psoriasis, how the extent of skin disease affects mortality risk, and whether the risk of mortality in patients with severe psoriasis is altered by various systemic therapies. Patients with severe psoriasis should receive comprehensive health assessments to enhance preventive health practices, improve overall health, and decrease the risk of mortality."
The Trustees of the University of Pennsylvania and the National Institute of Arthritis and Musculoskeletal and Skin Diseases supported this study. Some of the study authors have disclosed various financial relationships with Amgen Inc, Astellas Pharma Inc, Biogen Idec, Centocor, Genentech Inc, Novartis, Warner Chilcott, Wyeth, Johnson & Johnson, Abbott Laboratories, Bristol-Myers Squibb, and the US Food and Drug Administration.
Arch Dermatol. 2007;143:1493-1499.

Long-Term Etanercept (Enbrel) Found Safe and Effective for Psoriasis

HOUSTON, June 18 -- Psoriasis patients who had extended exposure to high-dose etanercept (Enbrel) responded well without increased infections or other serious adverse effects, researchers here reported.
Exposure-adjusted event rates for serious noninfectious adverse events and infection rates for up to 96 weeks of etanercept treatment were similar to those for placebo, reported Stephen Tyring, M.D., Ph.D., of the University of Texas here, and colleagues, in the June issue of the Archives of Dermatology.
In a phase III, randomized, double-blind trial with an open-label extension, 618 adults with moderate to severe plaque psoriasis were studied at 39 centers in the U.S. and Canada from May 23, 2003 through June 22, 2005.
Three hundred and seven patients were randomized to placebo treatment for the first 12 weeks, and 311 were given twice-weekly subcutaneous injections of 50 mg of etanercept.
Beginning with week 13, all patients, 591 at that point, were given etanercept. During the open-label part of the study, assessments were done every 12 weeks. Patients given etanercept from the start took the drug for up to 96 weeks.
Of the total patient population, 67.6% were men, 89.2% were white, and the mean age was 45.7. On average, the duration of psoriasis was 19.9 years, with 27.2% of the body surface affected.
There were antibodies to etanercept, determined to be non-neutralizing, in 18.3% of patients, but they had no apparent effect on safety or efficacy, the researchers reported.
Patients responded within two weeks to etanercept, with statistically significant differences between the treated and placebo groups at week 12 in the Psoriasis Area and Severity Index, the researchers reported.
However, at week 24, after 12 weeks of open-label etanercept treatment, the patients in the original placebo group caught up to the etanercept patients with comparable clinical benefits, the researchers reported.
After 96 weeks of therapy, 51.1 % of the original etanercept-treated patients and 51.6% of those given placebo for the first 12 weeks had improvements from baseline of at least 75%.
The exposure-adjusted event rates of noninfectious adverse events for placebo and etanercept exposures were 418.8 and 158.0 per 100 patient-years, respectively.
The rates for serious noninfectious events per 100 patient-years were 6.1 for placebo exposure and 7.7 for etanercept patients.
The most frequently observed noninfectious adverse events per 100 patient-years for placebo and etanercept included headache (36.4 versus 9.2 events), injection-site hemorrhage (24.3 versus 5.8). arthralgia (19.7 versus 4.8), and back pain (4.6 versus 5.2).
The most common serious noninfectious adverse events reported for etanercept treatment were myocardial infarction, basal cell carcinoma, and depression. None of these was reported after placebo exposure.
The exposure-adjusted event rates for serious infections were similar for the placebo and etanercept treated patients (1.5 and 1.2 events per 100 patient-years), the researchers reported.
Serious events, such as gangrene, viral meningitis, diverticulitis, infectious enteritis, gastroenteritis, and localized staphylococcal infection were each reported in one patient. However, viral meningitis was the only serious infections considered possibly related to the drug, the researchers said.
Extended exposure to etanercept was generally well tolerated. However, interpretation of the safety data was limited by the open-label nature of the study and the fact that the total number of exposure years for placebo was much lower than that for etanercept, the researchers noted.
Exposure-adjusted rates of noninfectious and infectious adverse events were similar for the two drug-treated groups at week 12 and 96, indicating that extended exposure to etanercept did not increase the drug's toxicity. In addition, the researchers said, the safety profile observed in this study is consistent with results previously reported for the lower dose of twice weekly 25 mg.
Although loss of efficacy during long-term therapy was observed in a small subset, most patients maintained their high response for up to 96 weeks. This loss may have been due to a variety of reasons, the researchers said, including non-compliance with taking the drug, from weeks 48 to 96, inherent limitations in the assessments of the psoriasis-severity scores, and psoriaisis-specific factors that decrease TNF dependency of the disease in patients with TNF antagonists, the researchers said.
"This study represents, to our knowledge, the longest continuous exposure of patients with psoriasis to 50 mg of etanercept twice weekly and provides further insights into the safety and efficacy of high-dose etanercept therapy for the management of moderate to severe psoriasis," Dr. Tyring and his colleagues concluded.