Clinical considerations of efalizumab therapy in patients with psoriasis

Psoriasis is a chronic, incurable disease that often requires decades of therapy to maintain disease control. Efalizumab is a recombinant monoclonal IgG1 antibody approved for use in patients with chronic moderate-to-severe plaque psoriasis. To date, efalizumab has been evaluated extensively in more than 3500 patients, including in studies that have evaluated its efficacy and safety during extended use. Just as psoriasis fluctuates in severity, the response to treatment with efalizumab can vary among patients. On the basis of my personal experience managing patients in and out of clinical trials, most patients benefit from efalizumab. The possibility exists of intercurrent events during efalizumab therapy, such as the development of a transient localized papular eruption or mild arthralgia or, in a few patients, a generalized inflammatory flare or severe arthralgia. However, there are techniques to potentially manage these events in a manner that maximizes patient comfort and compliance. If dermatologists become comfortable recognizing the subset of patients who are overall excellent responders but develop a papular eruption or mild and manageable arthralgia, they will be able to readily incorporate this effective biologic into their daily practice. In this article, clinical trial data and case reports illustrate recommended patient management techniques and the substantial long-term benefits that psoriasis patients may realize with efalizumab therapy.     

Palmoplantar pustular psoriasis: successful therapy with efalizumab after non-response to infliximab

Palmoplantar pustular psoriasis (PPP) is a chronic inflammatory skin condition mainly characterized by recurrent eruptions of sterile pustules on erythematous skin; hyperkeratosis and fissures on the palms and soles are additional clinical features. Treatment options for PPP are unsatisfactory. We present a patient with a typical course of PPP that had previously received a broad range of topical and systemic antipsoriatic therapies. They all had to be discontinued due to ineffectiveness or side effects. Being aware of the high efficacy of infliximab in generalized pustular psoriasis, we initiated this therapy. An initial improvement was followed by a substantial flare after 7 months, during which a combination treatment of infliximab with methotrexate was administered. Only subsequent monotherapy with efalizumab led to complete clearing up of PPP after 10 to 12 weeks of treatment without any adverse effects. This indicates that efalizumab is potentially effective in PPP.     

A review of malignancies observed during efalizumab (Raptiva) clinical trials for plaque psoriasis

BACKGROUND: Psoriasis is a chronic, incurable immune-mediated disease. Most therapies used for moderate to severe psoriasis are immunosuppressive. Agents that depress immune function, including traditional psoriasis therapies, have been associated with an increased incidence of malignancies. Efalizumab is a recombinant monoclonal immunoglobulin G1 (IgG1) antibody approved for use in psoriasis patients. OBJECTIVES: To evaluate the incidence of malignancy in patients receiving efalizumab during clinical trials compared with placebo-treated patients, psoriasis patients from external cohorts and the general US population. METHODS: Patient data were pooled from multiple phase III placebo-controlled, open-label efalizumab clinical trials, and the incidence rate of reported malignancies was calculated as a function of patient years of observation. The results for the efalizumab-treated patients were compared with the data on psoriasis patients from insurance claims databases and a registry of events in the general population. RESULTS: The efalizumab- and placebo-treated patients had similar incidence rates of malignancy, including lymphoproliferative disease, solid tumor, malignant melanoma and nonmelanoma skin cancer. The incidence of nonmelanoma skin cancers, including basal cell carcinoma and squamous cell carcinoma, in patients receiving efalizumab or placebo was elevated relative to the external databases. CONCLUSIONS: These results suggest that efalizumab treatment does not increase a patient's risk for malignancy. The difference observed with nonmelanoma skin cancer may be due to biases introduced by the clinical trial methodology. Additional patient observation is necessary to ascertain whether a link exists between efalizumab therapy and nonmelanoma skin cancer above that normally observed in psoriasis patients.     

Erythroderma in two patients with psoriasis upon discontinuation of efalizumab treatment

Efalizumab is therapeutically effective in moderate to severe plaque psoriasis. Rebound after discontinuing therapy affects approximately 14% of patients, while erythroderma occurs in less than 1% of the treated population. In this case report, we describe two non-responding patients with severe plaque psoriasis who developed erythroderma after treatment was ceased. Non-responders are more likely to suffer from rebound. This article emphasizes the importance of close monitoring of non-responders to efalizumab after discontinuance of treatment.     

Biologic therapy for psoriasis: the T-cell-targeted therapies efalizumab and alefacept

During the past several years, a new generation of therapies for psoriasis has been in development. These biologic therapies target the activity of T lymphocytes and cytokines responsible for the inflammatory nature of this disease. The first article of this 2-part update reviewed the tumor necrosis factor (TNF) inhibitors, infliximab and etanercept. In this article, we will review 2 therapies that target the T cell, efalizumab and alefacept.     

New-onset, debilitating arthritis in psoriasis patients receiving efalizumab

Efalizumab is a humanized anti-CD11a monoclonal IgG(1) antibody approved for the treatment of moderate-to-severe plaque psoriasis. This case report describes two cases of new-onset debilitating psoriatic arthritis in patients with plaque psoriasis on long-standing efalizumab therapy, despite the fact that their skin disease was in remission. Although during the clinical trials, involving over 2,700 study subjects, arthralgia was seen only at a rate of 1-2% higher than in those subjects receiving placebo, the cases presented here are interesting in that it appears that efalizumab treatment 'uncoupled' the psoriatic arthritic component from the cutaneous disease. It can be speculated that a possible mechanism for efalizumab-induced psoriatic arthritis is related to the blockade of regulatory T cells from joint tissue.     

Efficacy and safety observed during 24 weeks of efalizumab therapy in patients with moderate to severe plaque psoriasis

OBJECTIVE: To assess the efficacy and safety of a 24-week course of efalizumab. DESIGN: Phase 3, randomized, double-blind, parallel-group, placebo-controlled 12-week study followed by a 12-week open-label study. SETTING: Outpatient dermatology clinics.Patients A total of 556 patients with moderate to severe chronic plaque psoriasis who were seeing an outpatient dermatologist were included in the study.Intervention For weeks 1 to 12, the 556 patients were randomized to receive 1 mg/kg of efalizumab weekly or placebo subcutaneously. For weeks 13 to 24, 516 of these patients received 1 mg/kg of efalizumab weekly. MAIN OUTCOME MEASURES: Proportion of patients with a 75% or greater improvement in Psoriasis Area and Severity Index (PASI-75), a 50% or greater improvement in PASI (PASI-50), static Physician's Global Assessment (sPGA) rating of minimal or clear, and improvements in Dermatology Life Quality Index (DLQI), itching scale, and Psoriasis Symptom Assessment (PSA) frequency and severity scores at weeks 12 and 24. Safety was evaluated by reviewing adverse events, laboratory parameters, vital signs, and anti-efalizumab antibodies. RESULTS: At week 12, 26.6% of efalizumab-treated patients achieved PASI-75 and 58.5% achieved PASI-50. After 24 weeks of continuous efalizumab therapy, PASI responses increased: 43.8% of patients achieved PASI-75 and 66.6% achieved PASI-50. The percentage of patients who achieved an sPGA rating of minimal or clear increased from 25.7% to 35.9%. The mean percentage of improvement in all patient-reported outcomes (DLQI, itching scale, and PSA frequency and severity scores) at week 12 was maintained at week 24 (DLQI, 49.2%; itching scale, 42.2%; PSA frequency, 47.6%; PSA severity, 47.3%). There was a decline in overall reported adverse events from weeks 1 to 12 (80.4%) to weeks 13 to 24 (63.2%) without evidence of cumulative toxic effects.Conclusion Extending efalizumab treatment from 12 to 24 weeks leads to improved efficacy and maintenance of quality of life with no evidence of cumulative toxic effects noted in patients with moderate to severe chronic plaque psoriasis.     

Treatment of nail psoriasis with efalizumab: a preliminary study

Nail involvement is common in psoriasis, affecting 50% to 80% of all patients with the disorder. Pain may accompany nail involvement, restricting daily living activities, and therapy is limited by issues of efficacy and safety. The cases of 4 participants who had been enrolled in a 3-year study of efalizumab for the treatment of chronic moderate to severe plaque psoriasis are presented in this preliminary study. In addition to the diagnosis of moderate to severe plaque psoriasis, each participant discussed in this report presented with nail involvement. These participants achieved clearance of their nail psoriasis within 19 to 33 weeks of efalizumab therapy. None of the participants demonstrated adverse effects during efalizumab therapy. Our experience with these participants suggests that efalizumab may help to improve psoriasis affecting the nails when used for the treatment of chronic moderate to severe plaque psoriasis.