Daniel B. Shin

Patients with severe psoriasis are at increased risk of cardiovascular mortality: cohort study using the General Practice Research Database

AIMS Psoriasis is a common chronic inflammatory T-helper cell-1/17 mediated skin disease. Recent studies suggest that psoriasis, particularly if severe, may be an independent risk factor for atherosclerosis, myocardial infarction (MI), and stroke. We conducted a cohort study using the General Practice Research Database to determine if severe psoriasis patients have an increased risk of cardiovascular (CV) mortality. METHODS AND RESULTS Severe psoriasis was defined as patients who received a psoriasis diagnosis and systemic therapy consistent with severe psoriasis (n = 3603). Up to four unexposed patients without psoriasis were selected from the same practices and start dates for each psoriasis patient (n = 14 330). For every death, the cause was determined by review of the electronic medical record. Severe psoriasis was an independent risk factor for CV mortality (HR 1.57; 95% CI 1.26, 1.96) when adjusting for age, sex, smoking, diabetes, hypertension, and hyperlipidaemia. Overall, severe psoriasis patients experienced one extra CV death per 283 patients per year, even when adjusting for major CV risk factors. The relative risk of CV mortality was modified by age. For example, the RR of CV death for a 40-year-old and 60-year-old with severe psoriasis was 2.69 (1.45, 4.99) and 1.92 (1.41, 2.62), respectively. The findings were robust to multiple sensitivity analyses. CONCLUSION Patients with severe psoriasis have an increased risk of CV mortality that is independent of traditional CV risk factors. Additional studies are needed to determine the mechanism of this association and the impact that control of psoriasis has on CV risk.

The risk of stroke in patients with psoriasis.

Psoriasis is a chronic Th-1 and Th-17 inflammatory disease. Chronic inflammation has also been associated with atherosclerosis and thrombosis. The purpose of this study was to determine the risk of stroke in patients with psoriasis. We conducted a population-based cohort study of patients seen by general practitioners participating in the General Practice Research Database in the United Kingdom, 1987-2002. Mild psoriasis was defined as any patient with a diagnostic code of psoriasis, but no history of systemic therapy. Severe psoriasis was defined as any patient with a diagnostic code of psoriasis and a history of systemic therapy consistent with severe psoriasis. The unexposed (control) population was composed of patients with no history of a psoriasis diagnostic code. When adjusting for major risk factors for stroke, both mild (hazard ratio (HR) 1.06, 95% confidence interval (CI) 1.0-1.1) and severe (1.43, 95% CI 1.1-1.9) psoriasis were independent risk factors for stroke. The excess risk of stroke attributable to psoriasis in patients with mild and severe disease was 1 in 4,115 per year and 1 in 530 per year, respectively. Patients with psoriasis, particularly if severe, have an increased risk of stroke that is not explained by major stroke risk factors identified in routine medical care.

Prevalence of Metabolic Syndrome in Patients with Psoriasis: A Population-Based Study in the United Kingdom

Increasing epidemiological evidence suggests independent associations between psoriasis and cardiovascular and metabolic disease. Our objective was to test the hypothesis that directly-assessed psoriasis severity relates to the prevalence of metabolic syndrome and its components. Population-based, cross-sectional study using computerized medical records from The Health Improvement Network Study population included individuals aged 45-65 years with psoriasis and practice-matched controls. Psoriasis diagnosis and extent were determined using provider-based questionnaires. Metabolic syndrome was defined using National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III criteria. 44,715 individuals were included: 4,065 with psoriasis and 40,650 controls. 2,044 participants had mild psoriasis (≤2% body surface area (BSA)), 1,377 had moderate (3-10% BSA), and 475 had severe psoriasis (>10% BSA). Psoriasis was associated with metabolic syndrome, adjusted odds ratio (OR) 1.41 (95% CI 1.31-1.51), varying in a “dose-response” manner, from mild (adj. OR 1.22, 95% CI 1.11-1.35) to severe psoriasis (adj. OR 1.98, 95% CI 1.62-2.43). Psoriasis is associated with metabolic syndrome and the association increases with increasing disease severity. Furthermore, associations with obesity, hypertriglyceridemia and hyperglycemia increase with increasing disease severity independent of other metabolic syndrome components. These findings suggest that screening for metabolic disease should be considered for psoriasis, especially when extensive.

Attributable Risk Estimate of Severe Psoriasis on Major Cardiovascular Events

BACKGROUND Recent studies suggest that psoriasis, particularly if severe, may be a risk factor for major adverse cardiac events, such as myocardial infarction, stroke, and mortality from cardiovascular disease. We compared the risk of major adverse cardiac events between patients with psoriasis and the general population and estimated the attributable risk of severe psoriasis. METHODS We performed a cohort study in the General Practice Research Database. Severe psoriasis was defined as receiving a psoriasis diagnosis and systemic therapy (N=3603). Up to 4 patients without psoriasis were selected from the same practices and start dates for each patient with psoriasis (N=14,330). RESULTS Severe psoriasis was a risk factor for major adverse cardiac events (hazard ratio 1.53; 95% confidence interval, 1.26-1.85) after adjusting for age, gender, diabetes, hypertension, tobacco use, and hyperlipidemia. After fully adjusted analysis, severe psoriasis conferred an additional 6.2% absolute risk of 10-year major adverse cardiac events. CONCLUSION Severe psoriasis confers an additional 6.2% absolute risk of a 10-year rate of major adverse cardiac events compared with the general population. This potentially has important therapeutic implications for cardiovascular risk stratification and prevention in patients with severe psoriasis. Future prospective studies are needed to validate these findings.

Psoriasis Severity and the Prevalence of Major Medical Comorbidity: A Population-Based Study

IMPORTANCE Despite the growing literature on comorbidity risks in psoriasis, there remains a critical knowledge gap on the degree to which objectively measured psoriasis severity may affect the prevalence of major medical comorbidity. OBJECTIVE To examine the prevalence of major medical comorbidity in patients with mild, moderate, or severe psoriasis, classified objectively based on body surface area involvement, compared with that in patients without psoriasis. DESIGN, SETTING, AND PARTICIPANTS Population-based cross-sectional study of patient data from United Kingdom-based electronic medical records; analysis included 9035 patients aged 25 to 64 years with psoriasis and 90,350 age- and practice-matched patients without psoriasis. MAIN OUTCOMES AND MEASURES Prevalence of major medical comorbidity included in the Charlson comorbidity index. RESULTS Among patients with psoriasis, 51.8%, 35.8%, and 12.4%, respectively, had mild, moderate, or severe disease based on body surface area criteria. The mean Charlson comorbidity index was increasingly higher in patients with mild (0.375 vs 0.347), moderate (0.398 vs 0.342), or severe psoriasis (0.450 vs 0.348) (each P < .05). Psoriasis overall was associated with higher prevalence of chronic pulmonary disease (adjusted odds ratio, 1.08; 95% CI, 1.02-1.15), diabetes mellitus (1.22; 1.11-1.35), diabetes with systemic complications (1.34; 1.11-1.62), mild liver disease (1.41; 1.12-1.76), myocardial infarction (1.34; 1.07-1.69), peptic ulcer disease (1.27; 1.03-1.58), peripheral vascular disease (1.38; 1.07-1.77), renal disease (1.28; 1.11-1.48), and rheumatologic disease (2.04; 1.71-2.42). Trend analysis revealed significant associations between psoriasis severity and each of the above comorbid diseases (each P < .05). CONCLUSIONS AND RELEVANCE The burdens of overall medical comorbidity and of specific comorbid diseases increase with increasing disease severity among patients with psoriasis. Physicians should be aware of these associations in providing comprehensive care to patients with psoriasis, especially those presenting with more severe disease.

The risk of infection and malignancy with tumor necrosis factor antagonists in adults with psoriatic disease: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND There is a need to better understand the safety of tumor necrosis factor (TNF) inhibitors in patients with psoriatic disease in whom TNF inhibitors are frequently used as monotherapy. OBJECTIVE We sought to examine the risks of infection and malignancy with the use of TNF antagonists in adult patients with psoriatic disease. METHODS We conducted a systematic search for trials of TNF antagonists for adults with plaque psoriasis and psoriatic arthritis. We included randomized, placebo-controlled trials of etanercept, infliximab, adalimumab, golimumab, and certolizumab for the treatment of plaque psoriasis and psoriatic arthritis. Twenty of 820 identified studies with a total of 6810 patients were included. Results were calculated using fixed effects models and reported as pooled odds ratios. RESULTS Odds ratios for overall infection and serious infection over a mean of 17.8 weeks were 1.18 (95% confidence interval [CI] 1.05-1.33) and 0.70 (95% CI 0.40-1.21), respectively. When adjusting for patient-years, the incidence rate ratio for overall infection was 1.01 (95% CI 0.92-1.11). The odds ratio for malignancy was 1.48 (95% CI 0.71-3.09) and 1.26 (95% CI 0.39-4.15) when nonmelanoma skin cancer was excluded. LIMITATIONS Short duration of follow-up and rarity of malignancies and serious infections are limitations. CONCLUSIONS There is a small increased risk of overall infection with the short-term use of TNF antagonists for psoriasis that may be attributable to differences in follow-up time between treatment and placebo groups. There was no evidence of an increased risk of serious infection and a statistically significant increased risk in cancer was not observed with short-term use of TNF inhibitors.

Increased Risk of Diabetes Mellitus and Likelihood of Receiving Diabetes Mellitus Treatment in Patients With Psoriasis

OBJECTIVE To assess the risk of incident diabetes mellitus (DM) in patients with psoriasis and to evaluate DM treatment patterns among patients with psoriasis and incident DM. DESIGN Population-based cohort study. SETTING United Kingdom-based electronic medical records. PATIENTS We matched 108 132 patients with psoriasis aged 18 to 90 years with 430 716 unexposed patients based on practice and time of visit. For our nested study, only patients who developed incident DM during our study time were included. MAIN OUTCOME MEASURES Incident DM and adjusted risk of pharmacotherapy among those with incident DM. RESULTS The fully adjusted hazard ratios (95% CIs) for incident DM were 1.14 (95% CI, 1.10-1.18), 1.11 (95% CI, 1.07-1.15), and 1.46 (95% CI, 1.30-1.65) in the overall, mild, and severe psoriasis groups, respectively. Among those with incident DM and severe psoriasis, the adjusted risk for receiving DM pharmacotherapy was 1.55 (95% CI, 1.15-2.10). CONCLUSIONS Our results suggest that psoriasis is an independent risk factor for the development of type 2 DM in a dose-dependent manner, and that patients with severe psoriasis who develop DM are more likely to receive systemic diabetic therapies in comparison with patients with DM but without psoriasis.

Risk of moderate to advanced kidney disease in patients with psoriasis: population based cohort study.

Objective To determine the risk of chronic kidney disease in patients with psoriasis. Design Population based cohort study and nested cross sectional study. Setting Electronic medical records database based in United Kingdom. Participants Cohort study: patients with psoriasis aged 18-90 each matched to up to five patients without psoriasis based on age, practice, and time of visit. Nested study: patients with psoriasis aged 25-64 with confirmed data on psoriasis severity, each matched to up to 10 patients without psoriasis based on age and practice. Main outcome measures Cohort study: incident moderate to advanced (stage 3 through 5) chronic kidney disease. Nested study: baseline prevalence of chronic kidney disease. Results 136 529 patients with mild psoriasis and 7354 patients with severe psoriasis based on treatment patterns were matched to 689 702 unaffected patients. The adjusted hazard ratios (95% confidence intervals) for incident chronic kidney disease were 1.05 (1.02 to 1.07), 0.99 (0.97 to 1.02), and 1.93 (1.79 to 2.08) in the overall, mild, and severe psoriasis groups, respectively. Age was a significant effect modifier in the severe psoriasis group, with age specific adjusted hazard ratios (95% confidence intervals) of 3.82 (3.15 to 4.64) and 2.00 (1.86 to 2.17) for patients aged 30 and 60, respectively. In the nested analysis of 8731 patients with psoriasis with measurements of affected body surface area matched to 87 310 patients without psoriasis, the adjusted odds ratios (95% confidence intervals) for chronic kidney disease were 0.89 (0.72 to 1.10), 1.36 (1.06 to 1.74), and 1.58 (1.07 to 2.34) in the mild, moderate, and severe psoriasis groups, respectively. Conclusions Moderate to severe psoriasis is associated with an increased risk of chronic kidney disease independent of traditional risk factors.

A prospective clinical trial of open-label etanercept for the treatment of hidradenitis suppurativa.

BACKGROUND Medical therapies for hidradenitis suppurativa (HS) are often ineffective. Tumor necrosis factor-alpha inhibitors may be a potential treatment for patients with moderate to severe HS. OBJECTIVES We sought to evaluate the safety and efficacy of etanercept for patients with severe HS. METHODS We conducted a phase II clinical trial of etanercept (50 mg/wk subcutaneously) in patients with moderate to severe HS. Efficacy was measured using a Physician Global Assessment and several secondary physician- and patient-reported outcome measures. Responders were classified as those achieving at least a 50% reduction on the Physician Global Assessment score at week 12 compared with baseline. RESULTS Only 3 of the 15 patients who entered the study were classified as responders (response rate of 20%; 95% confidence interval: 4.3-48.1) based on the intention-to-treat analysis. Dermatology Life Quality Index scores improved slightly from a median of 19 to 15 (P = .02). Comparison of baseline with week-12 Physician Global Assessment scores, and secondary outcome measures of lesion counts and patient pain scores, failed to show statistically significant improvement. Etanercept was generally well tolerated; however, two patients discontinued the study as a result of skin infections at the site of hidradenitis lesions requiring oral antibiotics. LIMITATIONS Lack of a control group and a small number of participants are limitations. CONCLUSIONS Our study demonstrated minimal evidence of clinically significant efficacy of etanercept (50 mg/wk subcutaneously) in the treatment of hidradenitis. Future studies using higher doses of etanercept are indicated; however, patients need to be carefully monitored for infection and other adverse events. Randomized, controlled trials will be necessary to demonstrate the risk-to-benefit ratio of tumor necrosis factor-alpha inhibitors in the treatment of hidradenitis.

The Risk of Cancer in Patients With Psoriasis: A Population-Based Cohort Study in the Health Improvement Network

IMPORTANCE The risk of cancer in patients with psoriasis remains a cause of special concern due to the chronic inflammatory nature of the disease, the use of immune-suppressive treatments and UV therapies, and the increased prevalence of comorbid, well-established risk factors for cancer, such as smoking and obesity, all of which may increase the risk of carcinogenesis. OBJECTIVE To compare the overall risk of cancer, and specific cancers of interest, in patients with psoriasis compared with patients without psoriasis. DESIGN, SETTING, AND PARTICIPANTS Population-based cohort study of patients ages 18 to 89 years with no medical history of human immunodeficiency virus, cancer, organ transplants, or hereditary disease (albinism and xeroderma pigmentosum), prior to the start date, conducted using The Health Improvement Network, a primary care medical records database in the United Kingdom. The data analyzed had been collected prospectively from 2002 through January 2014. The analysis was completed in August 2015. EXPOSURES OF INTEREST Patients with at least 1 diagnostic code for psoriasis were classified as having moderate-to-severe disease if they had been prescribed psoralen, methotrexate, cyclosporine, acitretin, adalimumab, etanercept, infliximab, or ustekinumab or phototherapy for psoriasis. Patients were classified as having mild disease if they never received treatment with any of these agents. MAIN OUTCOMES AND MEASURES Incident cancer diagnosis. RESULTS A total of 937,716 control group patients without psoriasis, matched on date and practice visit, and 198,366 patients with psoriasis (186,076 with mild psoriasis and 12,290 with moderate-to-severe disease) were included in the analysis. The adjusted hazard ratios (aHRs) with 95% CIs for any incident cancer excluding nonmelanoma skin cancer (NMSC) were 1.06 (95% CI, 1.02-1.09), 1.06 (95% CI, 1.02-1.09), and 1.08 (95% CI, 0.96-1.22) in the overall, mild, and severe psoriasis group. The aHRs for incident lymphoma were 1.34 (95% CI, 1.18-1.51), 1.31 (95% CI, 1.15-1.49), and 1.89 (95% CI, 1.25-2.86); for NMSC, 1.12 (95% CI, 1.07-1.16), 1.09 (95% CI, 1.05-1.13), and 1.61 (95% CI, 1.42-1.84); and for lung cancer, 1.15 (95% CI, 1.03-1.27), 1.12 (95% CI, 1.01-1.25), and 1.62 (95% CI, 1.16-2.28) in the overall, mild, and severe psoriasis groups, respectively. No significant association was seen with cancer of the breast, colon, prostate, or leukemia. CONCLUSIONS AND RELEVANCE The association between psoriasis and cancer, albeit small, was present in our cohort of patients with psoriasis. This association was primarily driven by NMSC, lymphoma, and lung cancer.