Despite a wide range of topical and systemic treatment options, there is still no cure for psoriasis. But the need for safe and effective therapies, along with an improved understanding of the pathogenesis of the condition, has led to the development of a new generation of targeted biologic therapies. The goal of these agents is to induce and maintain remission of psoriasis so that the disease no longer interferes substantially with a patient’s quality of life.1,2 It appears that these drugs will have fewer side effects than methotrexate and cyclosporine, the current oral mainstays for generalized psoriasis, and will be more convenient than phototherapy, which must be administered two or three times a week. 

Three biologics are approved specifically for the treatment of moderate-to-severe stable plaque psoriasis; two arthritis agents are also effective. Their mechanism and administration vary.3,4 The efficacy of a biologic is usually expressed as improvement in a patient’s Psoriasis Area and Severity Index (PASI), a measure of overall psoriasis severity and coverage. The higher the PASI, the more severe the psoriasis.

Biologic agents are expensive; most cost more than $10,000 a year. In terms of efficacy, safety, and cost-effectiveness, UVB phototherapy appears to be the best first-line agent for the control of psoriasis, while biologics are a second-line agent. However, for patients who do not respond to light therapy, find it too inconvenient, or need better disease control, biologic therapy should be considered.

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Alefacept (Amevive; Biogen)

Evidence that T lymphocytes induce and sustain the disease process in psoriasis has led to the development of alefacept (human leukocyte function antigen [LFA]-3-IgG1 fusion protein), a recombinant protein that inhibits the activation of memory effector T lymphocytes and modifies the inflammatory process.5 In a phase III trial, more than two thirds of patients who received two 12-week courses of IV alefacept achieved a ≥50% reduction in PASI. Although most of the improvement came from the first course of therapy, a further increase in efficacy was observed after the second.6 In a subsequent phase III trial, IM administration of alefacept at 15 mg/week was shown to be a convenient, well-tolerated, and effective alternative to IV dosing.

Despite the reduction of memory effector T lymphocytes in patients treated with alefacept, no clinically significant signs of immunosuppression, opportunistic infections, or increase in malignancy has been observed. Adverse events may include serious infections, malignancies, lymphopenia, and hypersensitivity reactions. Since it is an immunosuppressant, alefacept should not be initiated in patients with reduced CD4+ lymphocyte counts. Patients receiving alefacept should undergo weekly monitoring of T-cell counts and discontinue therapy if counts fall below 250 cells/µL. Alefacept is a pregnancy category B drug (pregnant women should take it only if it is clearly needed) and is not approved for use in children. 

Efalizumab (Raptiva; Genentech)

Efalizumab is a humanized monoclonal antibody against CD11a, a subunit of LFA-1. LFA-1 is a T-cell surface molecule important in T-cell activation, T-cell emigration into skin, and cytotoxic T-cell function. In phase III trials, compared with placebo, significantly more patients who received subcutaneous (SC) efalizumab showed an improvement in PASI of 50% or 75% after 12 weeks.8,9 Extension of therapy for 12 weeks more provided continued clinical benefit, while discontinuation of therapy resulted in regression of PASI scores toward baseline values. Among patients who had at least 50% improvement in PASI, the time to relapse was approximately 84 days.8 

Common adverse events include a flulike syndrome consisting of headache, chills, fever, nausea, and myalgias within two days of treatment.8,9 A conditioning dose of 0.7 mg/kg is recommended to reduce the incidence and severity of reactions associated with the start of treatment. Subsequently, efalizumab should be given weekly at a dose of 1.0 mg/kg continuously. 

Administration of efalizumab was associated with a transient increase of circulating lymphocytes that persisted for the duration of treatment.8 There is no evidence of increased risk of end-organ toxicity, malignancy, or infection.3 In rare instances, use can lead to thrombocytopenia, and platelet counts should be checked during use. In addition, discontinuance of the drug can, rarely, lead to a rebound of psoriasis. This seems to occur in fewer than 1% of cases and suggests that patients stopping efalizumab should be transitioned to another medication.

Like other biologics, efalizumab is an immunosuppressive drug and should not be given to patients with infections, malignancy, or history of malignancy. Furthermore, vaccines should not be administered during efalizumab therapy. In a small clinical study, a single 0.3-mg/kg IV dose of efalizumab (equivalent to 1 mg/kg administered SC) given before primary immunization with a neoantigen decreased the secondary immune response, and a dose of 1 mg/kg almost completely ablated it.