Psoriasis: Leonardi CL

Gottlieb A, Korman NJ, Gordon KB, Feldman SR, Lebwohl M, Koo JY, Van Voorhees AS, Elmets CA, Leonardi CL, Beutner KR, Bhushan R, Menter A. · Department of Dermatology, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA. · J Am Acad Dermatol. · Pubmed #18423261 No free full text.

Abstract: Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this second of 5 sections of the guidelines of care for psoriasis, we give an overview of psoriatic arthritis including its cardinal clinical features, pathogenesis, prognosis, classification, assessment tools used to evaluate psoriatic arthritis, and the approach to treatment. Although patients with mild to moderate psoriatic arthritis may be treated with nonsteroidal anti-inflammatory drugs and/or intra-articular steroid injections, the use of disease-modifying antirheumatic drugs, particularly methotrexate, along with the biologic agents, are considered the standard of care in patients with more significant psoriatic arthritis. We will discuss the use of disease-modifying antirheumatic drugs and the biologic therapies in the treatment of patients with moderate to severe psoriatic arthritis.

Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB, Lebwohl M, Koo JY, Elmets CA, Korman NJ, Beutner KR, Bhushan R. · Baylor University Medical Center, Dallas, Texas, USA. · J Am Acad Dermatol. · Pubmed #18423260 No free full text.

Abstract: Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this first of 5 sections of the guidelines of care for psoriasis, we discuss the classification of psoriasis; associated comorbidities including autoimmune diseases, cardiovascular risk, psychiatric/psychologic issues, and cancer risk; along with assessment tools for skin disease and quality-of-life issues. Finally, we will discuss the safety and efficacy of the biologic treatments used to treat patients with psoriasis.

Pariser DM, Gordon KB, Papp KA, Leonardi CL, Kwon P, Compton PG, Rundle AC, Walicke PA, Lebwohl M. · Department of Dermatology, Eastern Virginia Medical School, Norfolk, VA, USA. · J Cutan Med Surg. · Pubmed #16699904 No free full text.

Abstract: 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.

Menter A, Leonardi CL, Sterry W, Bos JD, Papp KA. · Baylor University Medical Center, Dallas, Texas, USA. · J Am Acad Dermatol. · Pubmed #16488340 No free full text.

This publication has no abstract.

Leonardi CL. · Department of Dermatology, St. Louis University School of Medicine, 1755 S Grand, St. Louis, MO 63104, USA. · Dermatol Clin. · Pubmed #15450338 No free full text.

Abstract: 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.

Leonardi CL. · Saint Louis University School of Medicine and Central Dermatology, Saint Louis, Missouri , USA. · Dermatol Ther. · Pubmed #15379774 No free full text.

Abstract: 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.

Leonardi CL. · Department of Dermatology, Saint Louis University School of Medicine, 1034 South Brentwood Boulevard, Suite 600, St Louis, MO 63117, USA. · J Am Acad Dermatol. · Pubmed #12894132 No free full text.

Abstract: 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.

Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang Y, Li S, Dooley LT, Gordon KB, Anonymous00034. · Saint Louis University Medical School, St Louis, MO, USA. · Lancet. · Pubmed #18486739 No free full text.

Abstract: BACKGROUND: Interleukins 12 and 23 have important roles in the pathophysiology of psoriasis. We assessed ustekinumab, a human monoclonal antibody directed against these cytokines, for the treatment of psoriasis. METHODS: In this phase III, parallel, double-blind, placebo-controlled study, 766 patients with moderate-to-severe psoriasis were randomly assigned to receive ustekinumab 45 mg (n=255) or 90 mg (n=256) at weeks 0 and 4 and then every 12 weeks; or placebo (n=255) at weeks 0 and 4, with subsequent crossover to ustekinumab at week 12. Patients who were initially randomised to receive ustekinumab at week 0 who achieved long-term response (at least 75% improvement in psoriasis area and severity index [PASI 75] at weeks 28 and 40) were re-randomised at week 40 to maintenance ustekinumab or withdrawal from treatment until loss of response. Both randomisations were done with a minimisation method via a centralised interactive voice response system. The primary endpoint was the proportion of patients achieving PASI 75 at week 12. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00267969. FINDINGS: All randomised patients were included in the efficacy analysis. 171 (67.1%) patients receiving ustekinumab 45 mg, 170 (66.4%) receiving ustekinumab 90 mg, and eight (3.1%) receiving placebo achieved PASI 75 at week 12 (difference in response rate vs placebo 63.9%, 95% CI 57.8-70.1, p<0.0001 for 45 mg and 63.3%, 57.1-69.4, p<0.0001 for 90 mg). At week 40, long-term response had been achieved by 150 patients in the 45 mg group and 172 patients in the 90 mg group. Of these, 162 patients were randomly assigned to maintenance ustekinumab and 160 to withdrawal. PASI 75 response was better maintained to at least 1 year in those receiving maintenance ustekinumab than in those withdrawn from treatment at week 40 (p<0.0001 by log-rank test). During the placebo-controlled phase, adverse events occurred in 278 (54.5%) of the 510 patients receiving ustekinumab and 123 (48.2%) of the 255 receiving placebo. Serious adverse events occurred in six (1.2%) of 510 patients receiving ustekinumab and in two (0.8%) of 255 receiving placebo in this phase. The pattern of adverse events was much the same in the placebo crossover and randomised withdrawal phases as it was in the placebo-controlled phase. INTERPRETATION: Ustekinumab seems to be efficacious for the treatment of moderate-to-severe psoriasis; dosing every 12 weeks maintains efficacy for at least a year in most patients.

Revicki DA, Willian MK, Menter A, Gordon KB, Kimball AB, Leonardi CL, Langley RG, Kimel M, Okun M. · Center for Health Outcomes Research, United BioSource Corporation, 7101 Wisconsin Avenue, Bethesda, MD 20814, USA. · J Dermatolog Treat. · Pubmed #18058494 No free full text.

Abstract: OBJECTIVE: The effect of adalimumab on patient-reported outcomes (PROs) was evaluated in patients with moderate to severe psoriasis during the initial 16-week, double-blind period of a 52-week, Phase III, multicenter trial. METHODS: Patients were randomized to placebo or adalimumab 80 mg at Week 0 and 40 mg every other week from Week 1 to Week 15. PROs were evaluated throughout the study and included the Dermatology Life Quality Index (DLQI), the Short Form 36 Health Survey (SF-36), the Work Productivity and Activity Impairment Questionnaire-Specific Health Problem (WPAI-SHP), and several patient-rated symptom scales. RESULTS: The adalimumab-treated group reported significantly greater improvements in DLQI total score (p<0.001), SF-36 Physical Component Summary score (p<0.001), and Mental Component Summary score (p<0.001) compared with the placebo-treated group over 16 weeks. Significant differences, favoring adalimumab, were also seen for the DLQI subscale scores (p < 0.001); SF-36 scale scores (p<0.001); WPAI-SHP work impairment (p<0.001), activity limitation (p<0.001), and overall work impairment scores (p<0.001); patient's global assessment of disease severity (p<0.001), psoriasis pain (p<0.001), and psoriasis-related pruritus (p = 0.002). CONCLUSION: Adalimumab was efficacious in improving dermatology-specific and general health-related quality of life, work and activity limitations, and psoriasis-related symptoms in patients with moderate to severe psoriasis over a 16-week period.

Menter A, Tyring SK, Gordon K, Kimball AB, Leonardi CL, Langley RG, Strober BE, Kaul M, Gu Y, Okun M, Papp K. · Division of Dermatology, Baylor Research Institute, University of Texas Southwestern Medical School, 3900 Junius St, 125, Dallas, TX 75246-1613, USA. · J Am Acad Dermatol. · Pubmed #17936411 No free full text.

Abstract: BACKGROUND: Adalimumab is a fully human monoclonal antibody that binds tumor necrosis factor, a key proinflammatory cytokine involved in the pathogenesis of psoriasis. OBJECTIVE: We sought to evaluate clinical efficacy and safety of adalimumab for moderate to severe psoriasis and investigate continuous versus interrupted therapy. METHODS: We conducted a 52-week, multicenter study of 1212 patients randomized to receive adalimumab (40 mg) or placebo every other week for the first 15 weeks. At least 75% improvement in the Psoriasis Area and Severity Index (PASI) score was the criterion for advancement through this multiphase study. RESULTS: At week 16, 71% (578 of 814) of adalimumab- and 7% (26 of 398) of placebo-treated patients achieved greater than or equal to 75% improvement in the PASI score. During weeks 33 to 52, the percentage of patients rerandomized to placebo who lost adequate response (defined as <50% improvement in the PASI response relative to baseline and at least a 6-point increase in PASI score from week 33) was 28% compared with 5% of patients treated continuously with adalimumab. LIMITATIONS: Lack of an active comparator and evaluation of maintenance of response beyond week 52 are limitations. CONCLUSION: Adalimumab is efficacious and well-tolerated in the treatment of chronic plaque psoriasis. TRIAL REGISTRATION: Clinical trials.gov. NCT00237887.

Papp KA, Miller B, Gordon KB, Caro I, Kwon P, Compton PG, Leonardi CL, Anonymous00148. · Probity Medical Research, Waterloo, Ontario, Canada. · J Am Acad Dermatol. · Pubmed #16488338 No free full text.

Abstract: 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.

Gottlieb AB, Hamilton T, Caro I, Kwon P, Compton PG, Leonardi CL, Anonymous00147. · University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901-0019, USA. · J Am Acad Dermatol. · Pubmed #16488337 No free full text.

Abstract: 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.

Gordon KB, Bonish BK, Patel T, Leonardi CL, Nickoloff BJ. · Department of Internal Medicine, Division of Dermatology, Loyola University Medical Center, Maywood, IL 60153, USA. · Br J Dermatol. · Pubmed #16225604 No free full text.

Abstract: BACKGROUND: The pathophysiology of psoriasis is poorly understood, and the mechanism of action of biological agents interfering with tumour necrosis factor (TNF)-alpha that improve psoriatic plaques is completely unknown. OBJECTIVES: To begin to unravel the mechanism of action, cellular changes occurring in plaques following administration of adalimumab, a humanized monoclonal antibody against TNF-alpha, were investigated. METHODS: Thirteen different patients underwent sequential biopsies as part of a clinical trial. Each biopsy was immunostained and evaluated to calculate the relative density of epidermal Langerhans cells (LCs) before and after treatment (days 2, 7, 28, 84). To explore the basis for reduced epidermal LC densities in plaques, a SCID-Hu animal model was utilized. Acute psoriatic lesions were created within 2 weeks by injection of superantigen-activated CD4+ T cells into engrafted symptomless skin. RESULTS: Compared with symptomless skin, untreated plaques had a significantly reduced density of epidermal LCs. There was a rapid increase in density of epidermal LCs in plaques following treatment with adalimumab beginning as early as day 7. The paucity of epidermal LCs in plaques was contrasted to the prominent density of LCs in other skin disorders with chronic inflammation and alterations in keratinization, including lichen planus and inflamed seborrhoeic keratosis. Rapid creation of plaques using the SCID-Hu model was accompanied by loss of epidermal LCs, indicating that diminished LC density occurs at an early stage of lesion formation. CONCLUSIONS: These data shed light on a new immunopathological perspective highlighting a rapid loss of epidermal LCs in acute psoriatic lesions, with sustained decreased density of LCs in chronic plaques. Furthermore, an unexpected insight into the mechanism of action was uncovered for adalimumab, in which rapid restoration of epidermal LC density was observed.

Leonardi CL, Papp KA, Gordon KB, Menter A, Feldman SR, Caro I, Walicke PA, Compton PG, Gottlieb AB, Anonymous00028. · Saint Louis University School of Medicine, St. Louis, Missouri, USA. · J Am Acad Dermatol. · Pubmed #15761420 No free full text.

Abstract: 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.

Gottlieb AB, Gordon KB, Lebwohl MG, Caro I, Walicke PA, Li N, Leonardi CL, Anonymous00331. · Clinical Research Center, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08901-0019, USA. · J Drugs Dermatol. · Pubmed #15624744 No free full text.

Abstract: 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.

Leonardi CL, Powers JL, Matheson RT, Goffe BS, Zitnik R, Wang A, Gottlieb AB, Anonymous00396. · Saint Louis University School of Medicine, St. Louis, USA. · N Engl J Med. · Pubmed #14627786 links to  free full text

Abstract: 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.

Strober B, Berger E, Cather J, Cohen D, Crowley JJ, Gordon KB, Gottlieb A, Horn EJ, Kavanaugh AF, Korman NJ, Krueger GG, Leonardi CL, Menter A, Schwartzman S, Sobell JM, Young M. · Department of Dermatology, New York University Medical Center, New York, NY, USA. · J Am Acad Dermatol. · Pubmed #19527820 No free full text.

Abstract: Clinical trials for systemic psoriasis therapy typically enroll healthy patients and exclude patients with cardiovascular disease, latent tuberculosis, liver disease, histories of malignancies, viral infections, children, and pregnant or breast-feeding women. Physicians often require guidance for optimum management of severe psoriasis in patients that have a combination of underlying disease states. To provide treatment recommendations for complex psoriasis scenarios, a consensus panel comprising 15 experts in psoriatic disease convened to review and discuss available evidence-based data and to arrive at a consensus for treatment options of difficult cases. An application of the Delphi Method was used to select case scenarios, provide medical treatment options, present the case study with existing medical evidence, and anonymously vote on treatment options. The top 10 treatment options were ranked and statistically analyzed to compare the differences between treatments. The final rankings and analysis provide guidance for practical, safe, and efficacious treatment options in a number of complex psoriasis scenarios.

Leonardi CL. · St. Louis University, Central Dermatology, St. Louis, USA. · Manag Care. · Pubmed #18567143 No free full text.

Abstract: Psoriasis has not received widespread attention because, traditionally, dermatologists have not had effective treatments for moderate to severe manifestations of the disease.With a change in the understanding of the nature of psoriasis--from what had been thought to be a skin disease to what is now known to be an immune disorder--such therapies are now becoming available.

Hurley MY, George MN, Leonardi CL, Frater JL. · Departments of Dermatology (Hurley, George, Leonardi) and Pathology (Frater), Saint Louis University School of Medicine, St Louis, MO, USA. · Diagn Pathol. · Pubmed #18366773 links to  free full text

Abstract: ABSTRACT: BACKGROUND: Therapeutic biologic agents are uncommonly associated with lymphoma. CASE PRESENTATION: We report a patient with psoriasis treated with the biologic agents efalizumab (Raptiva(R)) and etanercept (Enbrel(R)), who developed painless lymphadenopathy with peripheral lymphocytosis during treatment, simulating a non-Hodgkin lymphoma clinically and pathologically. Lymphocytosis and lymphadenopathy spontaneously remitted following cessation of etanercept therapy and have not recurred. CONCLUSION: Distinction between clinically benign lymphoid proliferations related to antipsoriasis therapy and malignant lymphoma avoids the unnecessary use of anti-lymphoma chemotherapy.

Tom WL, Miller MD, Hurley MY, Suneja T, Kudva G, Leonardi CL, Obadiah JM. · Department of Dermatology, Saint Louis University School of Medicine, 1402 South Grand Blvd, MO 63104, USA. · Br J Dermatol. · Pubmed #17034539 No free full text.

Abstract: Efalizumab is a recombinant, humanized monoclonal anti-CD11a antibody used for the treatment of moderate to severe plaque psoriasis. Immune-mediated thrombocytopenia and anaemia have previously been reported with this therapy. We describe the first case of immune-mediated pancytopenia in a patient treated with efalizumab. Close monitoring of all blood cell counts is warranted in light of this case.

Leonardi CL, Toth D, Cather JC, Langley RG, Werther W, Compton P, Kwon P, Wetherill G, Curtin F, Menter A. · St. Louis University School of Medicine, St. Louis, Mo. 63117, USA. · Dermatology. · Pubmed #17033169 No free full text.

Abstract: 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.

Gottlieb AB, Leonardi CL, Goffe BS, Ortonne JP, van der Kerkhof PC, Zitnik R, Nakanishi A, Jahreis A. · Clinical Research Center, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08901-0019, USA. · J Am Acad Dermatol. · Pubmed #16488335 No free full text.

Abstract: 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.

Gordon KB, Gottlieb AB, Leonardi CL, Elewski BE, Wang A, Jahreis A, Zitnik R. · Loyola University, Maywood, IL, USA. · J Dermatolog Treat. · Pubmed #16467018 No free full text.

Abstract: 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.

Bansal C, Leonardi CL, Van Voorhees AS. · No affiliation provided · Int J Dermatol. · Pubmed #18986465 No free full text.

This publication has no abstract.

Leonardi CL, Strober BE. · No affiliation provided · J Am Acad Dermatol. · Pubmed #17052512 No free full text.

This publication has no abstract.