ABSTRACT
BACKGROUND: Psoriasis is a chronic inflammatory skin disease principally mediated by activated T cells, which release proinflammatory cytokines with reactive epidermal changes in the skin, producing the characteristic lesions of psoriasis. New research into possible treatment options has been inspired by increased understanding of the pathophysiology of psoriasis and advances in immunology and molecular biology permitting the development of targeted, highly active biologic agents. OBJECTIVE: The aim of this article is to provide practical guidelines for integration of these agents in the management of psoriasis.
Subject(s)
Biological Therapy , Psoriasis/drug therapy , Decision Trees , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Psoriasis is a chronic inflammatory skin disease principally mediated by activated T cells, which release proinflammatory cytokines with reactive epidermal changes in the skin, producing the characteristic lesions of psoriasis. New research into possible treatment options has been inspired by increased understanding of the pathophysiology of psoriasis and advances in immunology and molecular biology permitting the development of targeted, highly active biologic agents. OBJECTIVE: The aim of this article is to review the efficacy and safety of five biologic therapeutics in the treatment of moderate to severe psoriasis and to provide practical guidelines for integration of these agents in the management of psoriasis. METHODS: We searched MEDLINE (1966-2005) for articles containing the key words: alefacept, efalizumab, etanercept, infliximab, and adalimumab and searched recent conference abstracts. RESULTS: Emerging immunotherapeutic agents (fusion proteins, recombinant cytokines, fusion toxins, or antibodies) target T cells or cytokines responsible for plaque formation that is characteristic of psoriasis. Alefacept is the first biologic to be approved in both the United States and Canada. More recently, efalizumab and etanercept and infliximab have been approved in the United States and Canada for plaque-type psoriasis. Adalimumab is currently in phase III clinical trials. CONCLUSION: These novel biologics offer an intriguing and effective treatment option for patients with moderate to severe psoriasis.
Subject(s)
Biological Therapy/methods , Dermatologic Agents/therapeutic use , Psoriasis/therapy , Adalimumab , Alefacept , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , CD11 Antigens/therapeutic use , Etanercept , Humans , Immunoglobulin G/therapeutic use , Immunologic Factors/therapeutic use , Infliximab , Receptors, Tumor Necrosis Factor/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Tumor Necrosis Factor-alpha/antagonists & inhibitorsABSTRACT
BACKGROUND: Efalizumab (anti-CD11a), a targeted, reversible T-cell modulator, is a humanized monoclonal antibody that provides a rapid onset of action of clinical benefit and has been studied up to 36 months, showing continuous control of plaque-type psoriasis. Efalizumab has recently been approved in Canada for this indication. OBJECTIVE: To examine the efficacy and safety of efalizumab by presenting the latest data in the treatment of psoriasis. METHODS: We searched MEDLINE (1966-2005) for randomized, double-blind studies of efalizumab (1 mg/kg for 12 weeks) using the following key words: psoriasis, efalizumab, biologics, and treatment. RESULTS: It was found that the proportion of patients who achieved Psoriasis Area and Severity Index (PASI) 75 and PASI 50 ranged from 22 to 39% and 52 to 61%, respectively. PASI 75 improvement was achieved in 44% of patients, who continued to receive efalizumab by week 24. Following 36 months of continuous treatment, a PASI 75 response was achieved by 45% (intent-to-treat [ITT] analysis), 59% (maintenance group analysis), and 73% (as-treated analysis). Its safety profile was similar during the 12-week and 36-month treatment periods. CONCLUSIONS: Currently, more than 3,500 patients have received efalizumab in clinical trials. Efalizumab may be an important treatment option for dermatologists seeking to provide a well-tolerated and effective treatment modality for patients with moderate to severe chronic plaque psoriasis.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Immunosuppressive Agents/therapeutic use , Psoriasis/drug therapy , Antibodies, Monoclonal, Humanized , Humans , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
Psoriasis is a chronic, inflammatory skin disease. Historically, phototherapy or immunosuppressive agents have been the first line of treatment for patients with severe psoriasis; however, the long-term use of these agents is limited by dose-dependent toxicities. Alefacept was the first biological agent approved in both the US and Canada for the treatment of adults with moderate-to-severe chronic plaque psoriasis. Alefacept is a remittive therapy that selectively reduces memory T cells. The efficacy and safety of up to two courses of alefacept have been demonstrated in clinical trials, and thus, this review focuses on new data to optimise the use of this biological agent. Emerging data indicates that multiple courses of alefacept for the long-term treatment of psoriasis are safe and effective. In addition, data are reviewed on the use of alefacept in combination with other agents and in other diseases, including psoriatic arthritis.
Subject(s)
Psoriasis/drug therapy , Recombinant Fusion Proteins/therapeutic use , Alefacept , Combined Modality Therapy , Drug Administration Schedule , Humans , Multicenter Studies as Topic , Psoriasis/radiotherapy , Randomized Controlled Trials as Topic , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/pharmacokinetics , T-Lymphocytes/drug effects , Ultraviolet TherapyABSTRACT
BACKGROUND: Imiquimod is a topical immunomodulator that is indicated for the treatment of external genital and perianal warts. This drug has been recently approved for the treatment of actinic keratoses and superficial basal cell carcinoma. There is a growing body of evidence for its effectiveness in treating a variety of other skin conditions. OBJECTIVE: This review examines the role of imiquimod 5% cream in the treatment of skin diseases such as actinic keratoses, basal cell carcinoma, Bowen's disease, lentigo maligna, and extramammary Paget's disease. METHODS: Published literature containing the words "Imiquimod" or "Aldara" was reviewed and summarized. RESULTS: This agent has demonstrated indirect antiviral and antitumor effects in animal models. Although the exact mechanism of action is unknown, imiquimod is an agonist for toll-like receptor (TLR) 7 and is thought to act by inducing cytokines, such as interferon alpha (IFN-alpha), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNF-alpha). These cytokines trigger the immune system to recognize the presence of a viral infection or tumor and the associated lesion is ultimately eradicated. Side effects are generally well tolerated with local skin reactions reported most frequently. CONCLUSION: Imiquimod has been shown to be a safe and effective treatment for a variety of skin conditions.
