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Supplements Easing the Economic and Clinical Burden of Psoriasis and Psoriatic Arthritis: The Role of Managed Ca

Psoriasis and Psoriatic Arthritis Treatment

Alan Menter, MD
Over the past several years, an increased understanding of the pathophysiology of psoriasis and psoriatic arthritis has led to the development of several new biologic therapies.
Over the past several years, an increased understanding of the pathophysiology of psoriasis and psoriatic arthritis (PsA) has led to the development of several new biologic therapies. Appropriate treatment selection and timing may slow, and even halt, the progression of psoriasis and PsA; as a result, it can decrease the economic burden. As treatment options vary based on individual disease characteristics and patient preferences, reviewing the patient’s complete clinical picture is imperative. An updated treatment algorithm, based on patients’ most severe disease domain, is now available to guide the selection of optimal therapy. Special care should be given to patients with both psoriasis and PsA who experience multiple disease domains, a heavy symptom burden, and an increased risk of comorbidities.
Am J Manag Care. 2016;22:S225-S237
Overarching Principles of Psoriasis and Psoriatic Arthritis Treatment

     Several best practices have emerged to guide the management of patients with psoriasis and psoriatic arthritis (PsA). The current goals for treatment include minimizing disease activity, maintaining functional status, improving quality of life, and preventing or minimizing both disease- and treatment-related complications. The optimal choice of therapy may depend on disease severity, prognostic factors, prior treatment, comorbidities,access to therapy, and patient preferences.Multidisciplinary assessment and management are critical to addressing each aspect of PsA care. In addition, frequent monitoring and treatment adjustments will be necessary to achieve and maintain disease control.1

Lifestyle Modifications
     Smoking and obesity are examples of risk factors that exacerbate the signs and symptoms of psoriasis and/or PsA and contribute common comorbidities, such as cardiovascular disease.2 In addition, smoking can potentially reduce the effectiveness of anti-tumor necrosis factor-α (TNF-α) therapy.3 Nonpharmacologic interventions, such as smoking cessation, dietary advice, weight loss counseling and physical activity, are important components of comprehensive patient care.2 It is essential to diagnose signs or symptoms of psoriatic joint disease early to minimize, even prevent, joint destruction, as psoriatic joint disease usually takes 5 to 12 years to develop after the onset of skin psoriasis.4

Treat to Target
     The treat-to-target (T2T) principle of PsA management involves close monitoring and frequent treatment adjustments designed to achieve early and tight control of inflammatory disease activity. In the TICOPA trial, 206 patients with newly diagnosed PsA were randomly assigned to tight control using a T2T strategy or assigned to usual care. In the T2T arm, patients started treatment with methotrexate (MTX) that was escalated to 25 mg after 6 weeks. If patients did not achieve minimal disease activity by week 12, combination disease-modifying antirheumatic drug (DMARD) therapy was started. After
another 12 weeks, patients with residual disease activity started anti-TNF therapy or switched to an alternate DMARD in combination with MTX. By comparison, patients receiving standard care were seen every 3 months by a rheumatologist but otherwise followed no set treatment protocol.5
After 48 weeks, 62% of patients in the T2T arm achieved a 20% improvement from baseline in the American College of Rheumatology response criteria (ACR20) compared with 45% of patients in the standard care group (odds ratio [OR], 1.91; P = .0392). Patients managed with the T2T strategy were also more likely than those in the standard care group to gain control of the skin manifestations of psoriasis (59% vs 33%), defined as a reduction of 75% or more from baseline in the Psoriasis Area and Severity Index score (PASI 75). Although the frequency of adverse events (AEs) increased in the tight control group relative to standard care, most patients tolerated treatment well. The most common AEs were nausea, liver function abnormalities, and respiratory tract infections. These findings support the T2T strategy to improve outcomes across multiple measures in patients with early PsA, including those with skin involvement.5

Comorbidity Management
    Comorbidity screening and management are essential components of psoriasis and of PsA care. Several comorbidities occur with increased frequency in these patients including cardiovascular disease, diabetes, obesity, metabolic syndrome, osteoporosis, liver disease, and depression. Furthermore, patients with psoriasis and PsA are at an increased risk of exhibiting extra-articular manifestations of their underlying autoimmune disease, including inflammatory bowel disease and uveitis. Although the same comorbidity screening and management approaches apply to patients with psoriasis and PsA as to the general population, current guidelines stress the importance of identifying any comorbidities to provide optimal care for these patients.1
Treatment Options for Psoriasis and PsA
     Multiple treatment options, ranging from local therapies (ie, topical medications and phototherapy) to nonbiologic systemic therapies (nonsteroidal anti-inflammatory drugs [NSAIDs] and traditional
DMARDs) and biologics, are available for patients with psoriasis and PsA. Most clinical studies regarding psoriasis evaluate monotherapy and exclude even potent topical steroids as adjunctive therapy, whereas the majority of patients enrolled in PsA clinical studies will receive maintenance MTX, NSAIDs, and systemic steroids from the outset. In many cases, combination therapy is recommended to enhance treatment efficacy and minimize AEs.1,6,7 For instance, combining biologic agents such as etanercept or adalimumab with MTX results in greater control of psoriasis disease activity than either
agent alone. For patients experiencing psoriasis flares, the use of short-term cyclosporine in combination with other systemic or biologic agents is an effective strategy for reducing disease activity Furthermore, the combined use of biologic therapy, especially etanercept and phototherapy, is more effective against psoriatic lesions than either modality used alone.6 Additional combination regimens are reviewed in the following discussion of psoriasis and PsA therapies.

Local Therapies
Topical Therapies
      Topical medications are the first-line treatment option for the majority of patients with psoriasis who have limited disease, which is often defined as up to 5% of the body surface area (BSA). In addition, topical therapies continue to be used in adjunct with systemic therapies in patients with extensive disease (>5% BSA) who require more aggressive intervention. Options for topical treatment include emollients, topical corticosteroids, topical vitamin D analogs (eg, calcipotriene/calcipotriol, calcitriol, and tacalcitol), retinoids (eg, tazarotene), and calcineurin inhibitors (eg, topical tacrolimus 0.1% and
pimecrolimus 1%). In addition, a combination of a potent topical steroid and a vitamin D analogue in one preparation has shown to be effective. The amount of topical medication required to treat various BSA percentages can be gauged by the “fingertip unit” method, with 1 fingertip unit corresponding to approximately 2% BSA (Figure 17,8); this corresponds to approximately 500 mg.
     Multiple factors influence the choice of topical therapy, including body site, thickness and scaling of the psoriasis lesions, patient age, costs, and patient preferences. Poor adherence to topical medications is a major barrier to successful psoriasis treatment, with up to 40% of patients with psoriasis reporting nonadherence due to inconvenience, time constraints, frustration with medication efficacy, unclear instructions, and fear of AEs.7 Therefore, the successful use of topical medications requires a particular emphasis on patient education and counseling.

     Ultraviolet (UV) irradiation controls psoriatic skin lesions by targeting hyperproliferative epidermal cells and T-cells.9 Phototherapy is recommended as first-line therapy for moderate to severe psoriasis when skin involvement is too extensive for topical therapy alone. In addition, phototherapy is an appropriate treatment strategy for patients with limited skin involvement, but debilitating symptoms, such as those with severe psoriasis of the palms, soles, and scalp. For patients with PsA, phototherapy is also used to manage the cutaneous manifestations of psoriatic disease.10 Phototherapy is also appropriate in patients with contraindications to systemic treatment, such as women who are pregnant.9

Multiple phototherapy regimens are currently used in the outpatient setting.9 Pretreatment with topical or oral photosensitizing agents, such as psoralen, enhances the cytotoxic effects of UVA therapy and further inhibits epidermal cell proliferation. Photochemotherapy with oral psoralen and UV-A radiation (PUVA) can lead to dramatic improvements in psoriatic skin lesions.11 However, PUVA is less tolerated than UV-B-based phototherapy, with an increased risk of nonmelanoma skin cancer after 200 treatments. Phototherapy is costeffective for controlling psoriatic skin lesions but is less convenient for patients because of travel time and costs associated with absence from work.9 Thus, several home phototherapy units are available and prescribed under the guidance of dermatologists.

Nonbiologic Systemic Therapies
      NSAIDs play a central role in reducing inflammation and discomfort, particularly in patients with PsA with prominent axial disease, enthesitis, and dactylitis.1

Conventional DMARDs
     Traditional DMARDs, including MTX, sulfasalazine, leflunomide, and cyclosporine, are frequently used as first-line therapies for patients with PsA.12 In addition, these agents also form the backbone of many combination regimens for both skin and joints, such as MTX plus phototherapy for skin psoriasis, MTX plus biologic agents for skin and joints, or targeted small-molecule inhibitors. MTX is also the most commonly used systemic therapy worldwide for patients with moderate to severe psoriasis.13 Although highly effective as short-term monotherapy for skin psoriasis, cyclosporine is not nearly as effective for PsA. Conversely, neither sulfasalazine nor leflunomide, while helpful as adjunctive therapies for PsA, has an appreciable effect on skin psoriasis.14

Prior to initiating MTX, patients should be evaluated for potential drug–drug interactions (eg, MTX and sulfonamide-derived drugs), risk factors, and contraindications. Of note, MTX is absolutely contraindicated during pregnancy and breastfeeding. In the absence of contraindications, MTX is usually started at a dose of 10 to 15 mg/week and titrated to a maximum recommended dose of 25 mg/week. Although most patients begin treatment with oral MTX, parenteral administration is an option for patients who develop gastrointestinal intolerance, for those with an inadequate response to maximally titrated oral therapy, and in cases with high risk of nonadherence and/or dosing errors.13 In addition, MTX as monotherapy is highly effective in less than half of patients with psoriasis. The addition of oral folic acid (1-5 mg daily) is essential with MTX therapy to minimize adverse effects.

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