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Overview of Some Treatment Options for Plaque Psoriasis

Although there has been considerable progress in the understanding of the immunopathogenesis and genetics of psoriasis, there is no cure as yet. Treatment principles for patients with psoriasis include a durable remission, "substantial" improvement, maintenance therapy after initial improvement and minimization of significant side effects.¹ The therapeutic regimen recommended to the patient should be chosen based on the following considerations¹:

• Type(s) of psoriasis present in the patient
• Location of lesions (face, ears, hands, feet, genitalia and intertriginous areas, scalp, nails, trunk, extremities)
• Severity of lesions (thickness, redness, scaling) and nature of symptoms (pain, pruritus and others)
• Extent of disease/estimate of body surface area (BSA) involvement
• Psoriasis Area and Severity Index (PASI) score
• Age of patient and response to prior therapies
• Accessibility of dermatologist, hospital and phototherapy facilities
• Therapies available to treating physician and physician's preferences
• Economic factors relating to therapy options (cost/benefit ratios, third-party insurer's approval)
• Quality-of-life considerations (ability to perform daily activities, ability to work at a job, interpersonal relationships)
• Comorbid diseases/states, including childbearing potential, pregnancy or desire to impregnate, liver disease, hepatitis C or HIV infection, hypertension and alcohol consumption

Categorizing psoriasis patients as mild, moderate or severe can be challenging because severity is a qualitative determination that depends on disease activity, resistance to previous therapies and psychosocial factors.¹ Assignment of severity should be determined by patient history, examination and consideration of the aforementioned issues. Although a patient may have "mild" disease based on the percentage of BSA affected, phototherapy or systemic therapy may still be indicated if the patient is not responsive to topical agents or if daily activities and/or employment are disrupted. Patients are considered to have "moderate to severe" disease if the affected areas include the palms, soles, head and neck or genitalia and/or if there is involvement of more than 5% of BSA. Patients with moderate or severe psoriasis require more aggressive therapies.¹

The majority of patients with psoriasis have mild to moderate disease.² Mild to moderate psoriasis is generally managed with topical agents, either singularly or in combination, including^1,3,4:

• Vitamin D₃ analogs
• Corticosteroids
• Emollients
• Keratolytics, such as salicylic acid, lactic acid and urea
• Anthralin
• Coal tar
• Topical retinoids
• Lubricating agents

Vitamin D₃ and other topical agents may be appropriate for long-term use (up to 12 months), whereas topical corticosteroids (Table 1^3,4) are not generally indicated for chronic, long-term use because of the potential for adverse events.^2,5,6 Vitamin D analogs are thought to inhibit keratinocyte proliferation and modulate the activity of immune cells via binding and activation of the Vitamin D receptor on these cells to help normalize the keratinization process.^6-8

Topical corticosteroids are the most widely used medications for psoriasis in the United States and are effective at controlling inflammation, itching and scaling of lesions.³ Topically applied corticosteroid formulations have a high patient preference.³ They are available in ointment, cream, lotion, and gel preparations.³ Topical corticosteroid potency is determined according to the decrease in vasoconstriction that it causes (Table 1).^3,4

Table 1: Topical Corticosteroids^3,4

In addition to the aforementioned topical treatments, therapies for moderate to severe psoriasis can include any or all of the following¹:

• Phototherapy⁹
  • Narrowband-UVB light
  • Broadband-UVB light
  • Psoralen and UVA light (PUVA)
• Traditional systemic medications
  • Acitretin
  • Methotrexate
  • Cyclosporine
• Immunomodulatory biologic drugs¹⁰
  • Tumor necrosis factor (TNF) inhibitors: etanercept, adalimumab, infliximab
  • Pathogenic t-cell activation inhibitors: alefacept, efalizumab

Immunomodulatory biologics are a newer class of drugs that represent a significant advance in the treatment of psoriasis and psoriatic arthritis. Immunomodulatory biologics function by controlling the inflammatory response that underlies psoriasis. TNF inhibitors modulate inflammation by binding to and inhibiting TNF-α, a proinflammatory cytokine that is overexpressed in psoriatic skin and joints.¹⁰ Other immunobiologics target T-cell activation, thereby preventing the immunopathogenic cause of psoriasis. Alefacept, an engineered antibody, prevents T-cell activation and proliferation by binding directly to CD2 immunomodulatory molecules on the T-cell surface.¹⁰ Efalizumab, also an engineered antibody, blocks the process by which T cells become activated, traffic across blood vessels and become reactivated at sites of inflammation, such as psoriatic plaques.¹⁰ When considering the use of biologics, baseline laboratory studies must be performed to identify any underlying conditions or risk factors that may preclude the use of immunobiologics in some patients.¹⁰

Indeed, identifying an appropriate treatment strategy for patients with psoriasis is challenging, as it involves diligent consideration of the many therapeutic options.

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