Psoriasis and PsA: Beyond Skin and Joint Involvement
Psoriasis is a common, chronic, immune-mediated inflammatory, multisystem skin disease with potential systemic complications. Psoriatic arthritis (PsA) is a chronic inflammatory disease of the joints and connective tissue that often affect individuals with psoriasis. Both conditions may require long-term treatment and can impact activities of daily life as well as aspects of quality of life including psychological, social, and occupational elements. Currently, there is no known cure for psoriasis or PsA. However, the development of biologic agents and small molecule inhibitors have changed the treatment paradigm for dermatologists managing patients with these autoimmune diseases.
This article provides an overview of psoriasis and PsA and reviews the efficacy and safety of the newest biologic agent ixekizumab (Taltz) for psoriasis and the oral phosphodiesterase-4 (PDE4) inhibitor apremilast (Otzela) for psoriasis and PsA. The burden of disease including comorbidities, unmet patient needs, and cost is also covered. Additionally, 2 new drugs in development for psoriasis and PsA are reviewed.
Psoriasis and PsA Overview
Psoriasis, an often debilitating condition, is the most prevalent autoimmune disease, affecting 7.5 million people in the United States (approximately 3% of the US population). Of the individuals with psoriasis, 1.5 million US adults have moderate to severe psoriasis. The worldwide prevalence is estimated at 1% to 3%.1-3 Data from the National Psoriasis Foundation (NPF) estimates that approximately 25% of people with psoriasis have cases that are considered moderate.2 Men and women develop psoriasis at equal rates. Onset of psoriasis develops between the ages of 15 and 35, but it can develop at any age.4
The causes of psoriasis are not fully understood, but a number of risk factors are recognized, including family history and environmental risk factors. Psoriasis is characterized by scaly, erythematous patches, papules, and plaques that are often painful and pruritic.5 Psoriasis can be mild, moderate, or severe, and be classified on the extent of body surface area (BSA) involvement (Figures 1-4). The NPF defines mild psoriasis as affecting <3% of BSA, 3% to 10% of BSA is considered moderate, and >10% of BSA is considered severe. Five types of psoriasis exist and the majority of individuals (80%-90%) have plaque psoriasis (Table 1).4
Psoriasis is more than a cosmetic disorder; it has an emotional and physical impact beyond visible plaques as shared by individuals at a recent day-long patient-focused drug development meeting with the FDA in which individuals spoke to officials from the agency about psoriasis and how it impacts their lives. During the meeting, the FDA polled attendees on various aspects of the disease and reported the results in real-time. When asked what are the most bothersome impacts the disease has on daily life, 59% said emotional impacts. Attendees were also asked which benefit would they consider most meaningful when considering a new psoriasis treatment. The majority (64%) said reduced itching and flaking.6
Lewis-Beck and colleagues7 assessed the relationship between psoriasis self-reported severity of symptoms and health-related quality of life, work productivity, and activity impairment among 199 individuals with moderate to severe psoriasis. Individuals were more likely to miss work with increasing severity of itching (odds ratio [OR], 2.31), pain (OR, 1.78), and scaling (OR, 2.15) symptoms. More severe itching (OR, 1.74), scaling (OR, 1.84), and pain symptoms (OR, 1.53) increased the likelihood that an individual would be less productive at work.
PsA is an inflammatory seronegative spondyloarthropathy associated with psoriasis that can cause pain, swelling and stiffness in around the joints and tendons, nail changes, and overall fatigue. Genes, the immune system, and environmental factors are thought to play a role in the onset of the disease. The prevalence of PsA in the US general population has been estimated between 0.1% to 0.25%; up to 30% of people with psoriasis develop PsA.8,9 In the majority of cases, joint involvement follows skin involvement, often by 10 years. PsA usually develops between ages 30 and 50, but can develop at any time including childhood; the joint disease affects men and woman equally.3,8 Table 2 shows manifestations of PsA.
PsA symptoms can range from mild to very severe. The severity of the skin disease and the arthritis usually do not correlate with each other. Nail disease is commonly found in patients with PsA especially those with distal interphalangeal joint involvement. While PsA may start slowly with mild symptoms, the course of PsA is variable and unpredictable ranging from mild and nondestructive to a severe, debilitating, erosive arthropathy. If left untreated, individuals with PsA can have persistent inflammation, progressive joint damage, severe physical limitations, disability, and increased mortality.8,10
Like psoriasis, PsA can significantly impact quality of life. NPF research revealed that 63% of individuals with PsA are unable to be as active as they once were: 47% reported that the disease impacts their ability to work; and 34% said they have difficulty getting in and out of a car. Furthermore, individuals with PsA are not being diagnosed in a timely manner. Data showed 44% experience symptoms for 1 year or longer before being diagnosed and 30% reported a delay of 2 years or longer to receive diagnosis.11
Beyond the physical pain and discomfort of psoriasis and PsA, individuals with psoriatic diseases also face higher incidences of comorbidities including cardiovascular disease, diabetes, hypertension, and stroke.12 Hypertension in particular appears to be a leading comorbidity among patients with PsA. Husted and colleagues13 found that hypertension was present in 37% of PsA individuals compared with 20% individuals with only psoriasis. In the same comorbidity study, more individuals with PsA had neurologic conditions, gastrointestinal disorders, and liver disease than individuals with psoriasis alone.
In treating patients with PsA, Philip Mease, MD, clinical professor, University of Washington School of Medicine in Seattle, underscored the importance of looking at comorbidities. “It’s so important to think beyond the joints and skin,” he said during a session at the April Interdisciplinary Autoimmune Summit 2016 that focused on evolving treatment strategies for psoriatic disease. “[We need] to think about some of the associated manifestations including uveitis, inflammatory bowel disease, and comorbidity of cardiovascular disease and metabolic syndrome, fatty liver, depression, suicidal ideation, and fatigue.”
Compared with the general population, individuals with psoriasis have a higher prevalence of atherosclerosis, Crohn disease, cancer, metabolic syndrome, obesity, and liver disease.12 Psychological comorbidities have also been reported with psoriasis including depression, anxiety, and sleep disturbances affecting quality of life.14
Health care expenditures associated with psoriasis and PsA are significant. Brezinski and colleagues15 conducted a systematic review of 22 studies on the direct, indirect, and comorbidity costs of adult psoriasis in the United States. Individuals with psoriasis incur health care costs that are significantly greater than the general population. Additionally, the economic burden of psoriasis is substantial because this skin disease results in considerable negative physical, psychiatric, and social consequences. Adjusting costs to 2013 US dollars, the annual US cost of psoriasis is approximately $112 billion. The direct costs ranged from $51.7 billion to $63.2 billion, the indirect costs ranged from $23.9 billion to $35.4 billion, and medical comorbidities were estimated to contribute $36.4 billion annually.
Due to the dual skin and joint involvement, Feldman and colleagues16 found that individuals with moderate to severe psoriasis and comorbid PsA experience higher health care expenditures compared with matched controls free of both conditions. The retrospective study used data from a large US claims database to compare the comorbidities and health care utilization and costs between 1230 matched pairs of individuals with psoriasis and PsA and controls. Individuals with psoriasis and comorbid PsA compared with controls incurred substantially higher annual total health care costs ($27,123 vs $5301, respectively), with a majority of the cost difference driven by pharmacy costs ($18,083 vs $1267, respectively), followed by medical costs ($9040 vs $4035, respectively). Additionally, all medical cost components were higher among the cohort with psoriasis and PsA vs the matched controls, including inpatient services ($2372 vs $1456, respectively), emergency room ($294 vs $137, respectively), outpatient services ($5919 vs $2256, respectively), and other medical costs ($455 vs $185, respectively).
Unmet Patient Needs
The Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey aimed to further understand the unmet needs of psoriasis patients. The population-based survey included patients, dermatologists, and rheumatologists. The survey found that both psoriasis and PsA remain undertreated in patients with moderate to severe disease. Unmet needs identified in the management of these conditions included screening, assessment of disease severity, PsA diagnosis, and satisfaction with therapy.17 Among the patients with psoriasis, 26.9% had been diagnosed with PsA. Of those with psoriasis alone, fewer than 60% had seen a health care provider within 12 months compared with 85.6% of patients with PsA. Joint pain was reported by 51.8% of psoriasis patients without a PsA diagnosis, and 37.6% of dermatologists cited their greatest challenge as being differentiating PsA from other diseases.
Findings from MAPP survey also suggested that patients with psoriasis and dermatologists may assess disease severity differently. Itching was reported by 36.1% of psoriasis patients as the most important factor contributing to disease severity, followed by location and size of lesions (21.8%). In contrast, 76.2% of dermatologists considered the location or size of the skin lesion as the prominent factor contributing to disease severity in their patients, while only 11.9% cited itching. Patients also reported lower rates of current treatment than did dermatologists and rheumatologists. Conventional oral and biologic therapies were used by 24.9% and 17.7% of patients, respectively. Among patients who received injectable biologics, treatment dissatisfaction was related to long-term safety and tolerability, injection-related anxiety and fear, and cost. Overall, 31.3% of patients with psoriasis and 40.7% of patients with PsA reported that their primary goals of therapy, including keeping symptoms at bay, reducing itching, and decreasing flaking, were not met with their current treatment.17
Evidence has shown that individuals with PsA are often underdiagnosed or misdiagnosed, potentially leading to delays in treatment. Unmet needs and gaps in PsA diagnosis and treatment were identified by the Psoriatic Arthritis Forum.18 Gaps in awareness and diagnosis include minimal awareness of the PsA among physicians, appropriate screening tools for PsA are lacking, and criteria are unclear regarding rheumatologist referrals and/or treatment. Gaps in treatment included that available treatment algorithms have not been validated, no standard remission criteria, no available validated composite index combining physician- and patient-orientated outcomes, and the need for easy to use treatments with convenient means of administration.
“PsA is a complex heterogeneous disease, no patient is the same,” said Dr Mease, noting that clinicians need to consider the variabilities in the presentation when treating these individuals.
Article continues on page 2