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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
Although the PASI is a commonly used disease assessment tool, other measures are also used to assess psoriasis severity, such as BSA and the Physician Global Assessment (PGA), which provides an ordinal scale to assess psoriasis severity.38 In addition, the combined score of these 2 measures, known as s-MAPA, can also be used to assess disease severity.42 Other scoring metrics were developed with an intent to simplify PASI scoring. The Psoriasis Assessment Severity Score (PASS) and the simplified PASI (SPASI) were derived from PASI.38 In an effort to develop a more accurate measure of severity, the Psoriasis Log-Based Area and Severity Index (PLASI) and the Psoriasis Exact Area Severity Index (PEASI) were designed to include other important factors that the PASI score fails to consider.38

Clinical Practice Guidelines in the Treatment of Plaque Psoriasis

Guidelines for the management of plaque psoriasis developed by the American Academy of Dermatology indicate that treatment for psoriasis is guided by measures of disease severity (Figure 31,2,43). All patients should receive basic education on environmental triggers and methods to keep skin moisturized. Topical treatments are first-line therapy for mild psoriasis; corticosteroids, vitamin D analogues, or these may be used in combination with topical retinoids.43 Topical corticosteroid creams are the mainstay of treatment for the majority of patients with psoriasis with limited skin involvement or severity (<5% BSA). Challenges with topical treatment include incomplete clearance and inadherence.2 Corticosteroid creams and other topical applications can be used in combination with other treatments to enhance efficacy.2,43

Additional therapies for the treatment of plaque psoriasis may be needed for patients for whom treatment fails or who have more severe and extensive disease. As an alternative treatment option for these patients, phototherapy may provide effective and economical management without the potential toxicities of traditional and biologic therapies. Phototherapy can be administered in combination with topical agents, traditional systemic agents, or biologics for patients with moderate or severe disease.2 However, phototherapy may be limited by a lack of accessibility and inconvenient time commitment.2

Clinicians may escalate treatment with the use of traditional oral systemic agents for patients who do not achieve adequate response with phototherapy or topical treatment. Typically, an oral systemic agent is used for patients with initially extensive disease or severe psoriasis (BSA >10%). However, traditional oral systemic agents may also be appropriate for patients with limited disease with greater psoriasis symptoms which affect their QoL.44 Methotrexate, cyclosporine and the retinoid, acitretin, have been routinely used in clinical practice and have established long-term efficacy and organ toxicity profiles.2 Potential organ toxicities of oral systemic agents include liver, bone marrow, and kidney complications.44 In this way, patients must be carefully selected for treatment with traditional oral systemic agents and routinely monitored for adverse outcomes. Traditional oral systemic agents have a greater risk of organ toxicity compared with newer biologic agents.44

Biologic agents target specific molecules involved in the development of psoriatic plaques.1,2 In 2003, the FDA approved the first biologic agents that revolutionized psoriasis treatment.45 The introduction of newer agents provide additional options for patients with plaque psoriasis who require systemic treatment, as these newer agents may provide more effective and less toxic treatment alternatives compared with oral agents.2,44

Biologic agents vary in their mechanisms of action, mode of administration (subcutaneous or intravenous), immunogenicity, cost, availability within health plans, and indications for first or second-line therapy in the treatment of plaque psoriasis.46 Apremilast is an oral, nonbiologic agent indicated for the treatment of patients with moderate to severe plaque psoriasis.47 Its oral formulation provides an alternative to patients who may be unhappy with other treatments due to ineffectiveness, intolerability, or injection problems.48

Considerations in Treatment Selection and Efficacy Outcomes

As annual costs for biologics have been estimated to range from $13,000 to $30,000 per patient in the United States, considerations of treatment choice are important.41 Physicians and managed care professionals may also have different views about the selection of oral agents compared with biologic treatment due to the high costs and administration requirements of biologics.31 Payers may promote a step-wise treatment approach for moderate to severe psoriasis, incentivizing traditional systemic drugs as first-line treatments for patients who require escalated therapy. In contrast, physicians may prefer to initiate treatment with a more expensive biologic drug in patients with extensive disease.1,49

Costs from inadequately controlled disease, indirect costs, and expenses from worsening medical comorbidities may be considered when evaluating the cost-effectiveness of agents for the treatment of plaque psoriasis. Limitations of current investigations of cost analysis between biologics and oral agents include that studies do not account for costs of inadequately treated medical morbidities or adverse events (AEs) associated with the treatment selection and do not incorporate the effects of rapid treatment and sustained clearance. Moreover, cost comparisons have often used PASI 75 as a standard treatment goal despite this outcome reflecting an incomplete or nonresolution of psoriasis.31

The relationship between cost and physical and psychological functioning, as well as QoL was evaluating the relationship between measures of disease severity using the Dermatologic Life Quality Index (DLQI) and PASI and costs from a societal perspective in patients with plaque psoriasis not receiving biologic treatment. A stronger correlation was demonstrated between DLQI and cost compared with PASI and cost.50 Of patients not receiving biologics, high levels of impairments on the DLQI had greater overall costs, including indirect costs such as productivity losses. Patients receiving systemic therapy also had higher costs.50 Patients with a higher DLQI had higher costs associated with their plaque psoriasis compared with patients with less DLQI. The main cause of the cost discrepancy was lost production, followed by topical medication cost.50 The investigators concluded that biologics should be considered in patients with high DLQI scores.50

When comparing clinical trials, an important consideration arises from the changes in scoring metrics used to measure outcomes. In earlier trials, PASI 75 was the standard therapeutic goal and benchmark in many studies investigating. 45 However, with the advent of newer treatments PASI 90 and PASI 100 is becoming the emerging standard for evaluating therapeutic goals.40,45 Growing evidence supports the idea that PASI 90 and PASI 100 should be the new gold standard of efficacy assessment. Greater control and clearance of plaque not only manages the disease itself, but may also improve patients’ physical and psychological functioning and QoL, as assessed by the DLQI. 40

PASI values may be less beneficial in an immediate clinical setting. To help clinicians develop consistent targets in the management of plaque psoriasis, the NPF medical board conducted a consensus-building study.6 Using the Delphi technique, 25 experts from the NPF indicated that BSA was their preferred instrument to assess plaque psoriasis severity in clinical practice.6 The expert panel considered an acceptable response to initial therapy to be either an affected BSA of 3% of less, or a 75% or greater improvement from baseline to 3 months after treatment began.6 After this 3-month period, the experts recommend a treatment target BSA of 1% or less, with assessments at 6-month intervals throughout maintenance therapy.6

Following these recommendations, Wu and colleagues proposed a new nomenclature for BSA, such that a 75% improvement in BSA would be recognized as BSA 75, a 90% improvement would be noted as BSA 90, and a 100% improvement would become BSA 100. Such a classification schema would be analogous to improvements in the PASI 75, PASI 90, and PASI 100, respectively.5 These guidelines might serve as practical and straightforward tools to help clinicians monitor treatment response.5

Primary Endpoints in Clinical Trials

Patients with psoriasis who have an incomplete response to treatment may demonstrate substantial symptom burdens and effects on health-related QoL.51 In a secondary analysis of the phase 3 AMAGINE -1, AMAGINE -2, AMAGINE -3 trials, investigators pooled data from patients in the brodalumab arms who achieved at least PASI 75 during the trials to evaluate if achievement of complete skin clearance (PASI 100) significantly improved patient-reported QoL (DLQI) scores compared with patients who were almost cleared of the disease (PASI 75 or PASI 90). A greater proportion of patients who achieved PASI 100 demonstrated an absence of interference of psoriasis on daily life (DLQI score of 0 or 1) compared with  patients who were almost clear of disease; 62.7% of patients with skin clearance between PASI 90 and PASI 100 had DLQI scores of 0 or 1, compared with 80.2% of patients who achieved PASI 100 with brodalumab treatment. Additionally, a greater proportion of patients with PASI 100 had symptom-free days during the 12 weeks of follow up compared with patients who had skin clearance between PASI 75 and PASI 100 (10.5% vs 42.3%).51

The evolution of PASI endpoints deserves special consideration, as managed care providers may set standardized treatment goals at PASI 75. Earlier investigations of the safety and efficacy of agents used to treat psoriasis utilized PASI 75 as a primary end point, although PASI 90 was a key trial outcome.52-54 PASI 75 was a reasonable target for drugs such as tumor necrosis factor (TNF)  inhibitors, reflecting their overall efficacy.45 Some newer trials of potentially more efficacious drugs are still continuing to use PASI 75 as a primary endpoint, although PASI 90 and PASI 100 are often reported as secondary measures.48,55-57 PASI 75 is still the most commonly used measure of treatment response.58

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