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Contemporary Management of Moderate to Severe Plaque Psoriasis
Jashin J. Wu, MD

Contemporary Management of Moderate to Severe Plaque Psoriasis

Jashin J. Wu, MD
Psoriasis is a multisystem inflammatory disease that is often underdiagnosed, leaving many patients untreated. Plaque psoriasis, the most common form of the disease, affects approximately 80% to 90% of patients with psoriasis. Formulating a treatment plan can be complicated when various factors are considered. For example, type of therapy is dependent on the severity of the disease. Topical agents are preferred for mild disease, while phototherapy alone or in combination with systemic agents is recommended for the treatment of moderate to severe plaque psoriasis. Traditional systemic agents have the convenience of oral dosing; however, their toxicity profile can be a limiting factor. Newer biologic agents haven proven efficacious, if not superior to traditional oral agents, but their high cost can be a substantial disadvantage. Psoriasis has also been associated with increased risk of developing comorbidities, such as cardiovascular disease, obesity, and psoriatic arthritis, all of which increase the patient’s overall mortality and further worsen their overall physical well-being. Management of these comorbidities is often overlooked. Moreover, psoriasis may affect a patient’s psychological and social well-being. Patients with psoriasis are at a higher risk of developing clinical depression than patients without psoriasis. Inadequate management of comorbidities inevitably leads to poor outcomes, which increases the economic burden to the patient and society. Prevention and management of comorbidities, including cardiovascular and mental health, must be addressed as a part of a patient’s overall treatment plan. Specialist coordination may be beneficial for patients with psoriasis. Improved patient care may lead to better clinical and economical outcomes.
Am J Manag Care. 2017;23:S403-S416
Psoriasis is a multisystemic inflammatory disease that can substantially affect patients’ QoL (QoL). Psoriasis is characterized by skin papules, and plaques that are scaly, erythematous, painful, and pruritic.1 As a chronic condition, episodes of symptoms wax and wane over a patient’s lifetime and few patients experience spontaneous remission.1  Because this condition is frequently underdiagnosed, many patients with psoriasis remain untreated.2

In an analysis of National Health and Nutrition Examination Survey (NHANES) data collected from 2009 through 2010, the prevalence of psoriasis was 3.2% in Americans aged 20 to 59 years.3 Based on these data, it was estimated that in 2013 approximately 7.4 million adults older than 20 years were affected by psoriasis in the United States.3 However, this may be an underestimate of the true prevalence, as it did not account for those undiagnosed or patients with psoriasis who were younger than 20 years.3 Psoriasis is more common among adults than children, with 2 typical peaks of onset; the first peak at ages 20 to 30 years, and the second peak between ages 50 and 60 years.4  Psoriasis may be more common in non-Hispanic whites than in other ethnic groups.3 However, psoriasis is equally common in women and men.  

Plaque psoriasis, the most common form of psoriasis, affects approximately 80% to 90% of patients with psoriasis and is characterized by well-defined, erythematous plaques. Other forms of the disease include inverse, erythodermic, pustular and guttate psoriasis.1 Approximately 80% of patients with psoriasis have mild to moderate disease and the remainder have moderate to severe disease.2

Plaque Psoriasis Severity Rating Scales

Plaque psoriasis is diagnosed based on certain key physical manifestations. The well-defined erythematous plaques with white-silvery scales vary in size from 1 to a few centimeters. The irregular shaped plaques are most often located on the scalp, trunk, buttocks, limbs, and extensor surfaces. The severity of psoriasis is predominantly determined by the total body surface area (BSA) affected and the location, thickness, redness, and scaliness of the plaques; however, the impact of the disease on QoL is also an important consideration in clinical practice.2

Clinicians largely use BSA to evaluate psoriasis severity, as this value can be easily estimated in an office setting.5  The National Psoriasis Foundation (NPF) defines mild psoriasis as plaque affecting less than 3% of the BSA; moderate psoriasis as plaque affecting 3% to 10% BSA, and severe psoriasis as plaque affecting more than 10% BSA.6,7 Patients with mild disease may have only a few plaques covering less than 3% of BSA.6  Moderate to severe psoriasis is defined as psoriasis that affects 3% or more BSA or psoriasis present in vulnerable locations such as the hands, feet, face, and genital regions.1,6 The disease may also be considered more severe if it substantially impacts the patient’s psychological or physical well-being.2

Burden of Comorbid Conditions in Patients With Psoriasis

Psoriasis is associated with an increased risk of several medical comorbidities. The etiology behind this has not been fully elucidated, but presumably results from overlapping pathophysiology.8 It is known that the chronic inflammatory state characteristic of psoriasis affects other body systems. For example, chronic inflammation may predispose patients with psoriasis to obesity and atherosclerosis; or worsen these conditions if they are already present.8 Oxidative stress, common environmental factors, specific genes, psychosocial stressors, behavioral changes, and potential adverse therapy effects may also play an etiological role in these comorbidities.2,8,9 

Cardiovascular Disease

Patients with psoriasis have greater risk of cardiovascular (CV) events, and greater severity of the disease is associated with higher CV event rates. An increased risk of CV events in patients with psoriasis may be associated with the underlying the abnormal physiology of psoriasis. Alternatively, the relationship may be due to poor lifestyle choices, driven by the psychological impact of psoriasis, that contribute to obesity and CV decline.10

A cross-sectional study of more than 130,000 patients with psoriasis in the United Kingdom found an increased prevalence of diabetes (7.1% vs 3.3%), hypertension (20% vs 11.8%), elevated lipid levels (6% vs 3.3%), and smoking (30.1% vs 21.3%) compared with patients without psoriasis, respectively.11

The relationship between CV disease (CVD) and psoriasis was further demonstrated in a retrospective analysis of claims data from 2 large US healthcare databases. Patients with psoriasis demonstrated a 1.2-fold greater risk of atherosclerosis, congestive heart failure, type 2 diabetes (T2D), and peripheral vascular disease than patients without psoriasis. The highest rates of CVD or risk were demonstrated in patients with more severe psoriasis compared with mild disease.10

Patients with psoriasis also have an increased risk of overall mortality, largely due to CVD.2  Patients with severe psoriasis are 39% more likely to experience fatal CV events compared with patients without psoriasis (rate ratio [RR], 1.39; 95% CI, 1.11-1.74).  Fatal cardiovascular events occur at an incidence rate of 2.1 to 16.2 per 1000 person-years in this population (Table 112).12  Although the increased CV events and mortality associated was more pronounced in severe psoriasis, both mild psoriasis also contribute to the population risk of major adverse cardiovascular events.12

A recent prospective study of patients with psoriasis patients in the United Kingdom demonstrated an increased risk of early death, which was associated with comorbid CV conditions.13 Differences in mortality rates were investigated in adults with psoriasis (N = 8760) and without psoriasis (N = 87,600) after adjusting for confounders such as age, sex, and comorbidity scores. The investigators identified higher rates of multiple chronic diseases in patients with plaque psoriasis, including chronic kidney disease, diabetes, chronic obstructive pulmonary disease, and past myocardial infarction. Mortality rates were comparable between patients with and without psoriasis: 3.35 deaths per 1000 person-years compared with 2.12 deaths, respectively. However, in a stratified analysis of patients with psoriasis by BSA affected, patients with more than 10% of BSA affected had a significantly increased risk of mortality versus patients without psoriasis (HR, 2.12, 95% CI, 1.46-3.07). This increased mortality risk remained even after adjustment for comorbidities (HR, 1.79; 95% CI, 1.23-2.59).13

Metabolic Syndrome

Patients with metabolic syndrome are predisposed to coronary heart disease. Metabolic syndrome is defined as the presence of at least 3 of 5 specified metabolic risk factors in a single individual. These factors include elevated fasting glucose, elevated blood pressure, elevated triglycerides, and increased waist circumference.14 Patients with psoriasis were found to be at a greater risk of meeting the metabolic syndrome criteria (odds ratio [OR], 1.7-5.3).14 The underlying chronic inflammation of psoriasis may be a contributing factor in the pathophysiology of insulin resistance, visceral adiposity, hypertension, and dyslipidemia.9 Metabolic syndrome is also more likely in patients with severe psoriasis compared with those with mild disease.8

Obesity deserves special mention as a comorbidity in psoriasis. It contributes to a number of different health conditions, including CVD, T2D, obstructive sleep apnea, and osteoarthritis.15 Obesity has profound social and psychological impacts on patients. Obese patients report lower self-esteem due to social stigmatization and concerns about their appearance, and they experience bias in areas such as education and employment.16 A meta-analysis of 16 cross-sectional and case controlled studies showed that patients with psoriasis have greater than 50% odds of being obese compared with the general population. Moreover, the OR for obesity was significantly higher for patients with moderate to severe psoriasis compared with patients with mild disease. Additionally, patients with pre-existing psoriasis have a greater likelihood of becoming obese than do patients without psoriasis.15

A variety of mechanisms have been proposed for the association of obesity and psoriasis. These include underlying genetic and inflammatory mediators or adverse effects from certain medications.15 Psoriasis might also increase the risk of obesity via increased depression, alcohol use, and social isolation, as well as unhealthy eating habits and decreased physical activity.14 The association also proceeds in the other direction, as obesity may increase the risk of developing psoriasis.14 Partly as a result of this association, individuals with psoriasis are also at greater risk of T2D.17

Psoriatic Arthritis 

Psoriatic arthritis (PsA) is another major comorbidity occurring in a subgroup of patients with psoriasis. The incidence of PsA is unclear, but a meta-analysis placed it at approximately 6.4 per 100,000. In patients with psoriasis, the prevalence estimates range from 6% to 41%.18 It most commonly presents as an asymmetrical oligo-arthritis causing pain and swelling in the affected joints.18 The condition can sometimes predate skin problems, but more commonly appears in patients already exhibiting psoriasis.18 Notably, those with PsA can also have significant extra-articular comorbidities affecting the tendons and ligaments, eyes, gastrointestinal tract, heart, arteries, and urogenital system.18

In addition to these major more common comorbidities, psoriasis also increases the risk of other medical conditions. The risk of Crohn’s disease in patients with psoriasis is estimated to be between 3.8 and 7.5 times greater compared with the general population and patients with psoriasis may have a higher risk of multiple sclerosis and lymphoma.2

Psychological Distress and Mental Health

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