Long-term management of plaque psoriasis with continuous efalizumab therapy.
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Antibodies, Monoclonal↗
Biomedical subjects
Craig L Leonardi
Publications and source records attributed to Craig L Leonardi.
Efalizumab retreatment in patients with moderate to severe chronic plaque psoriasis.
BACKGROUND: Efalizumab targets T cell-mediated steps important in psoriasis immunopathogenesis. OBJECTIVE: We sought to evaluate the efficacy and safety of efalizumab retreatment in patients with moderate to severe plaque psoriasis. METHODS: In this open-label, phase III study, 365 patients who received efalizumab therapy during an earlier clinical trial were retreated with 12 weeks of subcutaneous efalizumab (1 mg/kg/wk) 35 days or more after their last dose of efalizumab. RESULTS: After 12 weeks of efalizumab retreatment, 56.9% of patients achieved 50% or more improvement from baseline Psoriasis Area and Severity Index (PASI) and 25.3% achieved at least 75% reduction in PASI score. The mean percentage PASI improvement from baseline was 51.2%. Overall, 76.1% of patients surveyed were "very satisfied" or "satisfied" with the efficacy of efalizumab. The safety profile of efalizumab retreatment was similar to that observed in patients receiving efalizumab for the first time. LIMITATIONS: Not all patients received sufficient exposure to efalizumab during their previous efalizumab clinical trial to allow for determination of their initial response to efalizumab. Of 365 patients enrolled in the study, 282 received at least 12 weeks of prior efalizumab therapy; of these patients, 208 (73.8%) achieved a PASI-50 response from their previous therapy. CONCLUSION: These results suggest that retreatment with efalizumab therapy is an efficacious option for patients who have previously discontinued treatment.
Adult↗
Etanercept monotherapy in patients with psoriasis: a summary of safety, based on an integrated multistudy database.
BACKGROUND: Etanercept, a tumor necrosis factor antagonist, is an approved treatment in the United States and Europe for plaque psoriasis. OBJECTIVE: To further examine the safety profile of etanercept in patients with chronic, moderate to severe plaque psoriasis. METHODS: Safety data from an integrated database of 1347 patients from 3 randomized, double-blind, placebo-controlled clinical trials were analyzed. Safety end points included incidence rates of adverse events, serious adverse events, infections, serious infections, injection site reactions, and routine laboratory assessments. Pooled safety results from the first 12 weeks of each trial are reported here. RESULTS: Rates of adverse events, serious adverse events, infections, and serious infections in the first 12 weeks of the 3 trials were similar among all active groups as well as each active group, compared with the placebo group. No dose-related toxicities were reported. LIMITATIONS: This report includes a relatively short (12-week) time frame; data from patients exposed to etanercept for longer periods are needed. CONCLUSIONS: Etanercept was generally safe in a large cohort of patients with moderate to severe plaque psoriasis.
Adult↗
Long-term continuous efalizumab therapy in patients with moderate to severe chronic plaque psoriasis: updated results from an ongoing trial.
BACKGROUND: Efalizumab is a T cell-targeted therapy for psoriasis. OBJECTIVE: We sought to evaluate the efficacy and safety of long-term, continuous efalizumab therapy. METHODS: Of 339 patients enrolled in this ongoing, open-label, phase III study, after 3 months 290 qualified for and entered the maintenance treatment phase. RESULTS: Results for the first 27 months of this 36-month continuous therapy trial are available. At month 3, 41% of patients achieved at least a 75% reduction in Psoriasis Area and Severity Index (PASI) score; at month 27, 47% achieved at least a 75% reduction in PASI score (intent to treat, n = 339). Among patients eligible for maintenance therapy (n = 290), 56% achieved at least a 75% reduction in PASI score at month 27. Moreover, the at least 90% reduction in PASI score rate increased through 18 months (33%). The safety profile with efalizumab was sustained throughout 27 months of continuous treatment with no new common events over time. LIMITATIONS: Because the extended treatment period was not a randomized clinical trial, no formal comparative analyses versus placebo were conducted. Three-month placebo data from randomized, parallel, placebo-controlled studies are briefly discussed. CONCLUSIONS: These results suggest that efalizumab maintains, and in some patients continues to improve, efficacy during long-term therapy.
Antibodies, Monoclonal↗
On multiple courses of alefacept.
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Alefacept↗
Clinical response in psoriasis patients discontinued from and then reinitiated on etanercept therapy.
BACKGROUND: Although continuous therapy with the tumor necrosis factor (TNF) antagonist, etanercept, has been shown to have a favorable benefit to risk profile in the treatment of moderate to severe plaque psoriasis, it is recognized that patients and practioners may wish for intermittent treatment should life circumstances dictate. OBJECTIVE: To evaluate safety and effect maintenance of etanercept retreatment in psoriasis. METHODS: Results of a 24-week, randomized, placebo-controlled, double-blind study were previously reported. Patients who responded at week 24 (improved ?50% in psoriasis area and severity index [PASI]) discontinued etanercept until disease relapse (loss of ?50% of week 24 PASI improvement). Patients were retreated with blinded etanercept at the originally randomized dose: 25 mg or 50 mg twice weekly (BIW) or 25 mg once weekly; original placebo patients received 25 mg BIW for the final 12 weeks of the double-blind period and were retreated with etanercept 25 mg BIW. RESULTS: Psoriasis returned gradually, without untoward events, within, on average, 3 months after etanercept discontinuation. Results after 12 weeks of retreatment were similar to those achieved after the initial 12 weeks. The major limitation of this study is that it examines only one round of discontinuation/retreatment. CONCLUSIONS: Retreatment with etanercept was effective and well tolerated in psoriasis patients.
Adult↗
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.
Antibodies, Monoclonal↗
Clinical efficacy of efalizumab in patients with chronic plaque psoriasis: results from three randomized placebo-controlled Phase III trials: part I.
BACKGROUND: Effective psoriasis therapies are needed for long-term symptom control. OBJECTIVE: Assess efalizumab (Raptiva) efficacy in a large cohort of psoriasis patients. METHODS: Data from three Phase III, randomized, double-blind, parallel-group, placebo-controlled, multicenter studies were pooled. Patients (n = 1,651) with moderate to severe plaque psoriasis received 12 weeks of subcutaneous efalizumab 1 or 2 mg/kg/wk or placebo. RESULTS: All efficacy measures reached statistical significance within each of the individual studies (p < 0.001) and overall. More efalizumab-treated patients achieved > or = 75% and > or = 50% Psoriasis Area and Severity Index (PASI) improvement at week 12 than did placebo-treated patients (27.8% vs 3.8% [p < 0.001] and 56.1% vs 14.6% [p < 0.001], respectively). Significant PASI improvements occurred as early as week 2 (12.5% vs 7.9%, p =0.0001). Adverse events were generally mild to moderate. CONCLUSION: Efalizumab resulted in early and significant improvement for all efficacy endpoints and was well tolerated in patients with moderate to severe chronic plaque psoriasis.
Adolescent↗
Extended efalizumab therapy improves chronic plaque psoriasis: results from a randomized phase III trial.
BACKGROUND: Efalizumab inhibits multiple T-cell-mediated processes. OBJECTIVE: To evaluate 12- and 24-week efalizumab therapy for psoriasis. METHODS: In this phase III, randomized, double-blind trial, 498 patients received subcutaneous 1 or 2 mg/kg/wk efalizumab or placebo for 12 weeks. Efalizumab-treated patients who achieved <75% Psoriasis Area and Severity Index improvement (PASI-75) were re-randomized to a second 12-week course of treatment. Results At week 12, 39% and 27% of efalizumab-treated patients (1 and 2 mg/kg, respectively) achieved PASI-75 (vs 2% placebo; P < .001, both dose groups). At week 24, an additional 20% of efalizumab-treated patients achieved PASI-75 (vs placebo 7%, P = .018). Efalizumab was well tolerated. CONCLUSION: Twelve-week efalizumab treatment resulted in significant improvement; extension of therapy to 24 weeks resulted in additional improvement in patients who initially had not achieved PASI-75. There were no significant changes in safety profile during weeks 13-24.
Adult↗
Current concepts and review of efalizumab in the treatment of psoriasis.
Efalizumab is a recombinant humanized monoclonal IgG1 antibody that targets CD11a, a cell surface protein that plays a key role in the T-cell-mediated steps leading to the pathogenesis of psoriasis. The efficacy and safety of efalizumab have been studied extensively in patients with moderate to severe chronic plaque psoriasis. Clinical trial data developed in several large phase 3 studies have demonstrated that efalizumab rapidly improves both physician- and patient-assessed measures of clinical efficacy, and that the observed changes are sustainable over extended periods of continuous treatment, with a favorable safety profile. Efalizumab represents a new therapeutic option for the long-term management of moderate to severe chronic plaque psoriasis.
Antibodies, Monoclonal↗
Efalizumab in the treatment of psoriasis.
Efalizumab is a humanized, monoclonal antibody, which targets CD11a, one of the subunits of leukocyte function-associated antigen-1. Administered subcutaneously once weekly, it decreases the activation of T lymphocytes as a primary or secondary process and interferes with the trafficking of T cells into sites of inflammation. Clinically, improvement in psoriasis can be observed as early as two to four weeks. The percent of patients experiencing a 75% reduction in PASI (PASI-75) was 27%, 44%, 47% at 12 weeks, 24 weeks, and 24 months, respectively. During the trials, the safety profile was highly favorable, with minor headaches and myalgias occurring after the initial doses. Rebound on abrupt discontinuation can be problematic for some patients and avoided by transition to an alternative therapy. Efalizumab appears to be a valuable option for patients requiring long-term control of their psoriasis.
Antibodies, Monoclonal↗
Etanercept as monotherapy in patients with psoriasis.
BACKGROUND: Inflammatory cytokines such as tumor necrosis factor (TNF) have been implicated in the pathogenesis of psoriasis. We evaluated the safety and efficacy of etanercept, a TNF antagonist, for the treatment of plaque psoriasis. METHODS: In this 24-week, double-blind study, 672 patients underwent randomization and 652 either received placebo or received etanercept subcutaneously at a low dose (25 mg once weekly), a medium dose (25 mg twice weekly), or a high dose (50 mg twice weekly). After 12 weeks, patients in the placebo group began twice-weekly treatment with 25 mg of etanercept. The primary measure of clinical response was the psoriasis area-and-severity index. RESULTS: At week 12, there was an improvement from base line of 75 percent or more in the psoriasis area-and-severity index in 4 percent of the patients in the placebo group, as compared with 14 percent of those in the low-dose--etanercept group, 34 percent in the medium-dose--etanercept group, and 49 percent in the high-dose-etanercept group (P<0.001 for all three comparisons with the placebo group). The clinical responses continued to improve with longer treatment. At week 24, there was at least a 75 percent improvement in the psoriasis area-and-severity index in 25 percent of the patients in the low-dose group, 44 percent of those in the medium-dose group, and 59 percent in the high-dose group. The responses as measured by improvements in the psoriasis area-and-severity index were paralleled by improvements in global assessments by physicians and the patients and in quality-of-life measures. Etanercept was generally well tolerated. CONCLUSIONS: The treatment of psoriasis with etanercept led to a significant reduction in the severity of disease over a period of 24 weeks.
Adult↗
Efalizumab: an overview.
Efalizumab (anti-CD11a), a targeted T cell modulator, is a humanized monoclonal antibody being studied for plaque psoriasis. Phase I and II studies demonstrated that efalizumab treatment results in histologic improvement and clinical benefit in patients with moderate to severe disease. Phase III clinical trials confirmed the clinical activity and safety of weekly efalizumab. Efalizumab is associated with a rapid onset of clinical benefit, with significant improvements observed as early as 4 weeks. Extending treatment from 12 to 24 weeks both maintains and improves the initial responses achieved at 12 weeks. Both 12 and 24 weeks of efalizumab therapy were generally well tolerated. Ongoing studies are being conducted to further define the optimal dosing and administration schedules for efalizumab in patients with moderate to severe plaque psoriasis.
Antibodies, Monoclonal↗
Extended efalizumab therapy sustains efficacy without increasing toxicity in patients with moderate to severe chronic plaque psoriasis.
Agents that safely provide long-term control of psoriasis are needed. To determine the safety and efficacy of extended efalizumab therapy, 339 patients with moderate to severe chronic plaque psoriasis received 2 mg/kg subcutaneous (SC) efalizumab weekly for 12 weeks. At Week 12, 290 patients who achieved > or =50% Psoriasis Area and Severity Index (PASI-50) improvement or a static Physician's Global Assessment grading of "mild," "minimal," or "clear" entered maintenance treatment with weekly SC efalizumab. At Week 12, 82%, 41%, and 13% of 339 patients achieved a PASI-50, PASI-75, and PASI-90 response, respectively. At 15 months, 65%, 50%, and 25% of patients achieved a PASI-50, PASI-75, and PASI-90 response, respectively (intent-to-treat, n = 339). The incidence of adverse events did not increase over time, and no new common adverse events were reported. The majority of patients experienced sustained efficacy with no increase in toxicity. This study is planned to continue; patients will receive up to 36 months of continuous efalizumab.
Adult↗