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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
Patients with psoriasis often feel stigmatized by their physical appearance, which may contribute to comorbid social isolation and stress-related disorders, such as depression and anxiety.19 Some evidence suggests that depression is more common in patients with psoriasis than in patients with other skin disorders, such as lichen planus or vitiligo.20 Prevalence estimates of depression in patients with psoriasis range from 6% to 62% depending on study-related factors (eg, design, population enrolled, definition criteria).19 A meta-analysis used pooled data from 98 studies to determine the prevalence and odds of depressive symptoms and clinical depression in patients with psoriasis. Of a large population of patients with psoriasis (N = 401,703), 28% showed symptoms of depression. Overall, patients with psoriasis were 1.5 times more likely to have clinical depression; approximately one-tenth were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria.19

Depression and psoriasis appear to have a complex pathophysiological relationship. In the United States, women with depression are more likely to experience new-onset psoriasis than men.20 In addition, a clear relationship has been elucidated between inflammation and depression; however, the extent of the pathological influence of depression or inflammation to each condition is unclear.21 Excessive alcohol use, which can exacerbate mental health morbidities, is more prevalent in patients with psoriasis compared with those without psoriasis.22

In a meta-analysis evaluating the relationship between psoriasis and suicide, risk of suicidal ideation was increased 2-fold in patients with psoriasis compared with patients without psoriasis (OR, 2.05; 95% CI, 1.54-2.74). Patients with psoriasis were also 32% more likely to attempt suicide (OR, 1.32; 95% CI, 1.14-1.54) and 20% more likely to complete suicide (OR, 1.20; 95% CI, 1.04-1.39).23 The severity of psoriasis was directly correlated with suicidal ideation and suicide attempts, where patients with more severe psoriasis were more likely to consider suicide and attempt suicide compared with those with more mild disease.23

The many medical comorbidities associated with psoriasis can decrease QoL. Worries about medical conditions and their consequences can put additional strains on mental health and further contribute to depression and anxiety.24 Conversely, poor mental health can exacerbate the health outcomes of these comorbidities. For example, patients with untreated depression may be less likely to take proper health preventative measures, and may demonstrate decreased ability to manage their needed medications.25 An analysis of NHANES data collected from over 30,000 patients demonstrated major depression in addition to a major medical condition is associated with greater healthcare utilization, more days spent in bed, greater functional disability, and higher productivity losses compared with patients without major depression.26

The comorbidity of PsA represents an additional psychological strain for patients with psoriasis. Patients with PsA have worse functional status, greater disability, and poorer QoL than patients with psoriasis who do not have PsA.27  Results of a large prospective cohort study also demonstrated an increased risk of incidence depression in women with psoriasis after adjusting for potential confounders, and an even greater risk for women with PsA. Multivariate-adjusted RRs of clinical depression were 1.29 (95% CI, 1.10-1.52) for women with psoriasis and 1.52 (95% CI, 1.06-2.19) for women with psoriasis and concomitant PsA compared with women without psoriasis.28

The impact of PsA on depression and suicidal ideation was investigated in patients with psoriasis. More than 36,000 patients with psoriasis, over 5000 patients with PsA and nearly 1900 patients with ankylosing spondylitis were enrolled. After adjusting for measurable confounders, all 3 study populations demonstrated an increased risk of depression. The IRR for psoriasis, PsA, and ankylosing spondylitis were 1.14 (95% CI, 1.11-1.17), 1.22 (95% CI, 1.16-1.29), and 1.34 (95% CI, 1.23-1.47), respectively.29 When researchers examined an endpoint that encompassed both suicidal ideation and suicide attempts, this measure was significantly higher in patients with PsA compared with the general population. In this study, this risk was not elevated in patients who  had psoriasis alone or in patients with ankylosing spondylitis.29 In 2017, the results of large prospective study of over 73,000 patients demonstrated that major depressive disorder increases the risk of PsA development as much as 37% in patients with psoriasis. In this way, managing depression in patients with psoriasis may be an important consideration for clinicians.30

Economic Burden of Psoriasis

Management of psoriasis can place a large economic burden on patients, especially those with more severe disease.31 Costs include direct disease expenses, costs from disease morbidities, and indirect costs such as from lack of productivity at work. Additional indirect costs can stem from restriction of activities and poor self-esteem due to the condition.32 In an analysis of data from 22 studies investigating costs associated with psoriasis in the United States, investigators estimated the annual overall economic burden of psoriasis ranged from $112 billion to $135 billion in 2013.32 The annual direct costs of psoriasis accounted for $52 billion to $64 billion of this total annual burden.32

In an analysis of a large US healthcare database, healthcare claims from 18,653 patients with psoriasis were used to categorize patients by all-cause total costs from 2011 to 2013, including healthcare resource utilization, treatment, and comorbidities costs. Patients in the highest-cost group accounted for 2.8% (n = 514) of all patients in the study, while patients in the lowest cost group (bottom 90% of expenditures in all 3 years), accounted for 79.8% (n = 14,891) of the study population.33 From 2011 to 2013, expenditures in the highest-cost group accounted for 13.3% to 13.7% of total annual costs, and 3.3% to 4.6% of psoriasis-related costs. All-cause costs this group were also 7.8-fold higher than in the lowest cost group with $68,913 and $8815, respectively. The lowest cost group accounted for approximately half of all-cause costs (50.7%-51.8%) and the majority of psoriasis-related costs (69.2%- 74.6%).33 Psoriasis-related medical and pharmacy costs were also higher in the highest-cost group ($8716) compared with the lowest-cost group ($4541).33

The management of comorbidities was the greatest expenditure contributing to the total economic burden of psoriasis.33 The highest-cost group presented with more comorbidities and there were significantly more patients with moderate or severe psoriasis in this group (40.7% vs 32.3%; P <.001). Patients in the group with the highest costs also had significantly more hospitalizations (36.8% vs 2.6%; P <.001) and psoriasis-related hospitalizations (11.1% vs 0.7%; P <.001) compared with the lowest-cost group.33

The annual costs of medical comorbidities in patients with psoriasis have been estimated at $36 billion in the United States.32 In patients with moderate to severe disease, a comorbid psychiatric disorder has the potential to add several thousands of dollars annually per patient.32  PsA, diabetes, hypertension, and obesity are just a few of the comorbid conditions that drive costs in the management of patients with psoriasis.32 Patients with comorbidities have higher direct and indirect costs, and require the use of more healthcare resources (Figure 134). In a retrospective US cohort analysis of over 56,000 patients with psoriasis, the mean annual adjusted direct cost differences for comorbid PsA, peripheral vascular disease and CVD were $9914, $8386, and $8275, respectively.34 Comorbidities also influenced indirect costs; the annual adjusted indirect costs were particularly high for cerebrovascular disease ($2501) and obesity ($2293).34

Without the inclusion of costs from medical comorbidities, the annual indirect costs from psoriasis have been estimated to range from $24 billion to $35 billion annually, including losses from work absenteeism and reduced work productivity (Table 232). Patients with moderate or severe disease may have increased limitations, such as reduced work productivity.35 Such indirect costs may account for up to 40% of the total economic burden of psoriasis.32

Patients with psoriasis have reported discrimination at work and difficulty in certain career paths related to their condition.36 The NPF investigated the impact of psoriasis on work status by analyzing survey data from more than 5600 patients with psoriasis (Figure 237). Patients with psoriasis were 1.8 times more likely to be unemployed compared with a matched unaffected population.37 Of the unemployed population with psoriasis, 92% reported psoriasis or PsA as the primary contributor. Of patients who were employed, nearly 50% reported missed work days due to the disease.37

Assessing Treatment Response

There are no measurable biomarkers that correlate with psoriasis severity. Clinicians often rely on clinical scoring systems to assess treatment response.38 The lack of clearly defined consensus treatment targets in psoriasis complicates analysis of best disease management.6

Psoriasis assessment tools, such as the Psoriasis Area and Severity Index (PASI), are often used in clinical trials. PASI scoring provides a uniform, objective measure of severity for comparison; thereby, reducing investigator bias.39 In clinical trials, the PASI is the traditional standard for assessing degree of psoriatic skin involvement.40 PASI provides a composite measure of both the signs and extent of psoriasis, entered into a formula that yields a score from 0 to 72.38,40 When comparing the efficacy of treatment options, researchers often rely on the PASI score as a measure of efficacy. A PASI success rate is reported as the percentage of patients that achieve a specific level of clearance of disease.41 A PASI 75 response represents a 75% reduction in the PASI score from baseline, or 75% disease clearance from the start to end of a clinical trial. PASI 90 represents a 90% reduction in the PASI score from baseline. Only  the PASI 100 response measure represents total disease clearance.40

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