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Craig L Leonardi - One of the best experts on this subject based on the ideXlab platform.

  • Efalizumab : results of a 3-year continuous dosing study for the long-term control of psoriasis
    The British journal of dermatology, 2008
    Co-Authors: Craig L Leonardi, Ivor Caro, Alan Menter, Tiffani K. Hamilton, B. Xing, Alice B. Gottlieb
    Abstract:

    Summary Background  Efalizumab, a T-cell-targeted, recombinant, humanized, monoclonal IgG1 antibody, inhibits key T-cell-mediated steps in the pathogenesis of psoriasis. Efalizumab is approved for the treatment of moderate-to-severe chronic plaque psoriasis in adults in more than 50 countries. Objectives  To evaluate the efficacy and safety of long-term, continuous Efalizumab therapy in patients with psoriasis. Methods  This open-label, multicentre phase III study enrolled 339 patients with moderate-to-severe chronic plaque psoriasis. During the initial 3-month phase, patients received subcutaneous Efalizumab 2 mg kg−1 weekly with randomization to receive concomitant fluocinolone acetonide or placebo ointment during month 3. The second phase was a long-term observational period; patients achieving a ≥ 50% improvement in the Psoriasis Area and Severity Index (PASI) score were eligible to receive Efalizumab 1 mg kg−1 weekly for up to 33 months. The final 3-month treatment period was an optional transition period for patients who completed the 33-month segment before Efalizumab became commercially available. Results  After 3 months, 41·3% of patients achieved a ≥ 75% improvement in PASI (PASI-75) and 13·0% achieved a ≥ 90% improvement (PASI-90). Continued improvement was observed: 45·4% and 24·5% achieved PASI-75 and PASI-90, respectively, at the end of the observational phase. The safety profile was stable, with no new or no increase in common events over 36 months of treatment. Conclusions  This was the longest continuous study using a biologic therapy for psoriasis. Clinical benefit of Efalizumab improved over the first 18 months and was maintained during 36 months of continuous therapy. Long-term Efalizumab therapy is appropriate for many patients with plaque psoriasis.

  • Efalizumab retreatment in patients with moderate to severe chronic plaque psoriasis.
    Journal of the American Academy of Dermatology, 2006
    Co-Authors: Kim A Papp, Bruce Miller, Kenneth B Gordon, Ivor Caro, Paul Kwon, Peter G Compton, Craig L Leonardi
    Abstract:

    Efalizumab targets T cell-mediated steps important in psoriasis immunopathogenesis. We sought to evaluate the efficacy and safety of Efalizumab retreatment in patients with moderate to severe plaque psoriasis. 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. 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. 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. These results suggest that retreatment with Efalizumab therapy is an efficacious option for patients who have previously discontinued treatment.

  • Efalizumab retreatment in patients with moderate to severe chronic plaque psoriasis
    Journal of the American Academy of Dermatology, 2006
    Co-Authors: Kim Papp, Kenneth B Gordon, Ivor Caro, Paul Kwon, Bruce E. Miller, Peter Compton, Craig L Leonardi
    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.

  • Practical guidelines for the long-term treatment of psoriasis with Efalizumab
    Journal of the American Academy of Dermatology, 2006
    Co-Authors: Craig L Leonardi, Kim Papp, Jan D. Bos
    Abstract:

    Greater understanding of the immunopathogenesis of psoriasis, combined with advances in molecular technology, has led to the development of biologic agents that target specific steps underlying this disease. 1 Biologics, which include T-cell inhibitors, such as Efalizumab andalefacept,andtumor necrosisfactor-ainhibitors, such as etanercept, infliximab, and adalimumab, differ from traditional therapies in terms of their mechanisms of action, modes of administration, and relative benefit:risk profiles favorable for safe, longterm control of disease. As the understanding and adoption of biologics are still at an early stage, it is important to provide guidance on how to incorporate these effective new therapies into clinical practice. In particular, the concept of long-term disease control, as is possible with Efalizumab, is relatively new, and dermatologists will benefit from learning how to initiate Efalizumab and maintain its continuous use. Efalizumab targets multiple T cellemediated processes important in the pathogenesis of psoriasis. The efficacy and safety of Efalizumab in psoriasis have been demonstrated in 15 clinical trials. The 4 reports included within this supplement provide important information and guidelines for dermatologists to consider when planning treatments and observing their patients during Efalizumab therapy. Efalizumab is designed to be administered continuously. The report by Gottlieb et al presents preliminary results from an ongoing, open-label, phase III trial evaluating the long-term continuous use of Efalizumab for up to 3 years. Data from this study support the maintenance of efficacy and a demonstrated safety profile in patients receiving up to 27 months of continuous Efalizumab therapy. During the course of therapy, patients may temporarily discontinue treatment for a variety of reasons. The report by Papp et al describes the results of an open-label, phase III trial evaluating the efficacy and safety of retreatment with Efalizumab in patients who completed participation in earlier Efalizumab clinical trials. The results demonstrate that retreatment with Efalizumab for an additional 12 weeks produced comparable response rates and a similar safety profile with those observed in patients receiving Efalizumab for the first time. An event that may occur on Efalizumab therapy

  • clinical efficacy of Efalizumab in patients with chronic plaque psoriasis results from three randomized placebo controlled phase iii trials part i
    Journal of Cutaneous Medicine and Surgery, 2005
    Co-Authors: David M. Pariser, Kim Papp, Kenneth B Gordon, Paul Kwon, Craig L Leonardi, Peter Compton, Patricia A. Walicke, Amy Chen Rundle, Mark Lebwohl
    Abstract:

    Effective psoriasis therapies are needed for long-term symptom control. Assess Efalizumab (Raptiva®) efficacy in a large cohort of psoriasis patients. 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. All efficacy measures reached statistical significance within each of the individual studies (p < 0.001) and overall. More Efalizumab-treated patients achieved ≥ 75% and ≥ 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. Efalizumab resulted in early and significant improvement for all efficacy endpoints and was well tolerated in patients with moderate to severe chronic plaque psoriasis.

Alan Menter - One of the best experts on this subject based on the ideXlab platform.

  • A retrospective analysis of 72 patients on prior Efalizumab subsequent to the time of voluntary market withdrawal in 2009.
    Journal of drugs in dermatology : JDD, 2014
    Co-Authors: Elizabeth Farley Prater, Antoinette Day, Mahir Patel, Alan Menter
    Abstract:

    Background Efalizumab was voluntarily withdrawn from the market in April 2009 after four cases of progressive multifocal leukoencephalopathy. Objective To review the baseline characteristics and psoriasis phenotypes of patients with prior excelled response to Efalizumab, and to determine the response of these patients to prior as well as subsequent therapies. By defining this subgroup of patients, particularly relating to palmoplantar psoriasis, future therapeutic considerations could be improved. Design A retrospective review of 72 patients who were on Efalizumab at the time of market withdrawal was conducted. Data was obtained through chart review of patients at a specialty psoriasis clinic in Dallas, TX. Main outcomes and measures Patient characteristics, details of Efalizumab use, and efficacy of Efalizumab compared with other psoriasis treatment modalities. Results Of the 72 patients, 24 (33%) were found to have palmoplantar disease. As a group, these patients were older, more likely to be female, and less likely to have a family history of psoriasis. 48 patients (67%) were on one or more systemic and/or biologic medication prior to starting Efalizumab. Their BSA improved from 5.45 to 0.8 as a group. Six patients were identified as having failed TNF alpha antagonist treatment prior to starting Efalizumab. All responded well to the medication with an average BSA of 0.54. Five of these six patients had evidence of palmoplantar disease prior to starting Efalizumab and five of these six patients were female. Eleven patients (15%) experienced neurologic side effects and 13 (18%) had infections while on Efalizumab treatment. Limitations This was a retrospective review. Quality of life issues could not always be fully assessed from the data available. Conclusions and relevance Efalizumab was effectively utilized in our clinical practice to treat patients with palmoplantar psoriasis, including six patients who had failed prior treatment with one or more TNF alpha antagonist agents.

  • Safety of Efalizumab Therapy in Patients with Moderate to Severe Psoriasis
    Drug Safety, 2008
    Co-Authors: Tiffani Hamilton, Ivor Caro, Peter Compton, Alan Menter, Jeffrey Sobell, Kim A Papp
    Abstract:

    Background: Psoriasis is a chronic autoimmune disease characterized by infiltration of the dermis and epidermis by activated T cells and the hyperproliferation and abnormal differentiation of keratinocytes. It is a life-long disease with alternating periods of remission and recurrence. Efalizumab is a humanized, recombinant, T-cell targeting monoclonal antibody, approved for use in adults with chronic moderate to severe plaque psoriasis. Objective: To assess the safety of continued or newly initiated treatment with Efalizumab for up to 48 weeks in patients with psoriasis who were treated previously with Efalizumab or placebo. Methods: This study was an open-label, 48-week extension of a previously published 12-week, randomized, double-blind, parallel-group, placebo-controlled, multicentre, phase IIIb study, carried out in the US and Canada between 24 October 2002 and 2 July 2004. Patients were followed and treated at the study clinic in an outpatient setting and also were trained to self-administer the drug at home. Patients comprising individuals with chronic moderate to severe plaque psoriasis who had completed the 12-week, placebo-controlled segment of the study were eligible for enrolment in the extension phase. Of the 686 patients enrolled in the study, 636 (92.7%) enrolled in the open-label extension of the study, 418 of whom had received 12 weeks of Efalizumab therapy and 218 of whom had received 12 weeks of placebo. All patients entering the open-label phase of the study received Efalizumab 1 mg/kg/wk for an additional 48 weeks, for a maximum exposure of up to 60 weeks. Safety was evaluated by an assessment of adverse events, including infections and serious adverse events. Results: The rate of withdrawal due to adverse events remained low throughout the trial, ranging from 1.2% to 6.6% during the 12-week segments of the open-label extension phase of the trial. The incidence of adverse events decreased with increased exposure to Efalizumab; the incidence during the initial 12 weeks of exposure to Efalizumab was 79.0% compared with 72.9% for patients exposed to placebo. Patients treated with Efalizumab for 13–24 weeks, 25–36 weeks, 37–8 weeks and 49–60 weeks experienced adverse events at an incidence of 66.8%, 54.3%, 49.6% and 48.5%, respectively. The incidence of serious adverse events ranged from 1.6% to 3.5% during the 12-week segments of Efalizumab therapy, compared with an incidence of 3.4% for placebo-treated patients. The incidence of infection ranged from 9.9% to 14.7% during the 12-week segments of Efalizumab therapy, compared with an incidence of 19.1% for placebo-treated patients. Malignancies were reported with an incidence of ≤1.0% for Efalizumab-treated patients during any 12-week segment compared with 0.4% for the 12-week placebo-treated patients. Of the 15 malignancies reported for Efalizumab-treated patients, 13 were basal cell (n = 4) or squamous cell (n = 9) carcinomas. Conclusions: These results support the short-term safety profile demonstrated for Efalizumab over a longer-term therapy period of up to 60 weeks.

  • Efalizumab : results of a 3-year continuous dosing study for the long-term control of psoriasis
    The British journal of dermatology, 2008
    Co-Authors: Craig L Leonardi, Ivor Caro, Alan Menter, Tiffani K. Hamilton, B. Xing, Alice B. Gottlieb
    Abstract:

    Summary Background  Efalizumab, a T-cell-targeted, recombinant, humanized, monoclonal IgG1 antibody, inhibits key T-cell-mediated steps in the pathogenesis of psoriasis. Efalizumab is approved for the treatment of moderate-to-severe chronic plaque psoriasis in adults in more than 50 countries. Objectives  To evaluate the efficacy and safety of long-term, continuous Efalizumab therapy in patients with psoriasis. Methods  This open-label, multicentre phase III study enrolled 339 patients with moderate-to-severe chronic plaque psoriasis. During the initial 3-month phase, patients received subcutaneous Efalizumab 2 mg kg−1 weekly with randomization to receive concomitant fluocinolone acetonide or placebo ointment during month 3. The second phase was a long-term observational period; patients achieving a ≥ 50% improvement in the Psoriasis Area and Severity Index (PASI) score were eligible to receive Efalizumab 1 mg kg−1 weekly for up to 33 months. The final 3-month treatment period was an optional transition period for patients who completed the 33-month segment before Efalizumab became commercially available. Results  After 3 months, 41·3% of patients achieved a ≥ 75% improvement in PASI (PASI-75) and 13·0% achieved a ≥ 90% improvement (PASI-90). Continued improvement was observed: 45·4% and 24·5% achieved PASI-75 and PASI-90, respectively, at the end of the observational phase. The safety profile was stable, with no new or no increase in common events over 36 months of treatment. Conclusions  This was the longest continuous study using a biologic therapy for psoriasis. Clinical benefit of Efalizumab improved over the first 18 months and was maintained during 36 months of continuous therapy. Long-term Efalizumab therapy is appropriate for many patients with plaque psoriasis.

  • Transitioning patients from Efalizumab to alternative psoriasis therapies: findings from an open-label, multicenter, Phase IIIb study.
    International journal of dermatology, 2007
    Co-Authors: Alan Menter, Paul Kwon, Tiffani K. Hamilton, Darryl Toth, Hoi M. Leung, Graham Wetherill, Brian Hennessey, Marvin Garovoy, David M. Pariser
    Abstract:

    Background  Rebound in psoriasis is, by definition, a rapid worsening of disease following the discontinuation of therapy for psoriasis; it occurs following the abrupt discontinuation of many therapies. To prevent rebound on discontinuation of Efalizumab, this study evaluated the effectiveness of transitioning patients to an alternative psoriasis therapy. Methods  Patients (n = 130) received subcutaneous Efalizumab 1 mg/kg/week for 12 weeks. Efalizumab was discontinued at 12 weeks; patients were evaluated for improvement from baseline in the Psoriasis Area and Severity Index (PASI) and a 12-week transition period was begun. Patients who achieved PASI improvement of 75% or more (PASI-75) at week 12 of Efalizumab treatment were observed during the transition period and treated only if psoriasis recurred. Patients who did not attain PASI-75 at week 12 of Efalizumab treatment were immediately transitioned to an alternative psoriasis therapy at the physician's discretion. All patients were evaluated for signs of rebound following Efalizumab discontinuation. Results  Rebound was not observed in any PASI-75 responder (n = 46). Rebound was observed in two of 32 patients who achieved between PASI-50 and PASI-75, and was more common in nonresponders (14/49). Rebound was observed in none of the eight patients treated with cyclosporine and in two of the 12 patients treated with methotrexate during the transition period. Conclusions  These results suggest that Efalizumab-responsive patients are less likely to experience rebound than nonresponders and may not require treatment until disease recurrence following Efalizumab discontinuation. Efalizumab nonresponders are at higher risk of developing rebound and thus should be considered for transition to an appropriate psoriasis therapy immediately following Efalizumab discontinuation.

  • safety of Efalizumab in adults with chronic moderate to severe plaque psoriasis a phase iiib randomized controlled trial
    International Journal of Dermatology, 2006
    Co-Authors: Kim Papp, Kenneth B Gordon, Ivor Caro, Patricia A. Walicke, Xiaolin Wang, Bernard S Goffe, Reni Bressinck, Scott Fretzin, Steven Kempers, Alan Menter
    Abstract:

    Background  To provide safety data for Efalizumab, a recombinant humanized monoclonal IgG1 antibody, in adults with chronic plaque psoriasis. Methods  A 12-week, Phase IIIb, randomized, double-blind, parallel-group, placebo-controlled trial. At 58 study sites in the USA and Canada, 686 patients with moderate to severe chronic plaque psoriasis received an initial conditioning dose of Efalizumab 0.7 mg/kg subcutaneously (SC) followed by either 11 weekly doses of Efalizumab 1 mg/kg SC or matching placebo. Main outcome measures were safety and tolerability outcomes (primary) and efficacy outcomes (secondary). Results  During 12 weeks of therapy with Efalizumab or placebo, the incidence of clinical adverse events was 82.2% and 72.9%, respectively; the incidence of serious adverse events was 1.8% and 3.4%, respectively; and the incidence of nonserious adverse events leading to withdrawal was 1.8% and 1.7%, respectively. In the Efalizumab group, there were no clinically significant changes in vital signs or laboratory parameters and no evidence of end-organ toxicities. A significantly higher proportion of patients receiving Efalizumab than those receiving placebo achieved ≥ 75% improvement in the Psoriasis Area and Severity Index (PASI) (P < 0.001), ≥ 50% improvement in PASI (P < 0.001), and a static Physician's Global Assessment rating of Minimal or Clear (P < 0.001). The mean improvement in the Psoriasis Symptom Assessment was significantly greater in the Efalizumab group (P < 0.001). Conclusions  Efalizumab treatment SC for 12 weeks was safe, well tolerated, and effective in patients with moderate to severe chronic plaque psoriasis.

Kenneth B Gordon - One of the best experts on this subject based on the ideXlab platform.

  • safety of Efalizumab in adults with chronic moderate to severe plaque psoriasis a phase iiib randomized controlled trial
    International Journal of Dermatology, 2006
    Co-Authors: Kim Papp, Kenneth B Gordon, Ivor Caro, Patricia A. Walicke, Xiaolin Wang, Bernard S Goffe, Reni Bressinck, Scott Fretzin, Steven Kempers, Alan Menter
    Abstract:

    Background  To provide safety data for Efalizumab, a recombinant humanized monoclonal IgG1 antibody, in adults with chronic plaque psoriasis. Methods  A 12-week, Phase IIIb, randomized, double-blind, parallel-group, placebo-controlled trial. At 58 study sites in the USA and Canada, 686 patients with moderate to severe chronic plaque psoriasis received an initial conditioning dose of Efalizumab 0.7 mg/kg subcutaneously (SC) followed by either 11 weekly doses of Efalizumab 1 mg/kg SC or matching placebo. Main outcome measures were safety and tolerability outcomes (primary) and efficacy outcomes (secondary). Results  During 12 weeks of therapy with Efalizumab or placebo, the incidence of clinical adverse events was 82.2% and 72.9%, respectively; the incidence of serious adverse events was 1.8% and 3.4%, respectively; and the incidence of nonserious adverse events leading to withdrawal was 1.8% and 1.7%, respectively. In the Efalizumab group, there were no clinically significant changes in vital signs or laboratory parameters and no evidence of end-organ toxicities. A significantly higher proportion of patients receiving Efalizumab than those receiving placebo achieved ≥ 75% improvement in the Psoriasis Area and Severity Index (PASI) (P < 0.001), ≥ 50% improvement in PASI (P < 0.001), and a static Physician's Global Assessment rating of Minimal or Clear (P < 0.001). The mean improvement in the Psoriasis Symptom Assessment was significantly greater in the Efalizumab group (P < 0.001). Conclusions  Efalizumab treatment SC for 12 weeks was safe, well tolerated, and effective in patients with moderate to severe chronic plaque psoriasis.

  • Efalizumab retreatment in patients with moderate to severe chronic plaque psoriasis.
    Journal of the American Academy of Dermatology, 2006
    Co-Authors: Kim A Papp, Bruce Miller, Kenneth B Gordon, Ivor Caro, Paul Kwon, Peter G Compton, Craig L Leonardi
    Abstract:

    Efalizumab targets T cell-mediated steps important in psoriasis immunopathogenesis. We sought to evaluate the efficacy and safety of Efalizumab retreatment in patients with moderate to severe plaque psoriasis. 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. 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. 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. These results suggest that retreatment with Efalizumab therapy is an efficacious option for patients who have previously discontinued treatment.

  • Efalizumab retreatment in patients with moderate to severe chronic plaque psoriasis
    Journal of the American Academy of Dermatology, 2006
    Co-Authors: Kim Papp, Kenneth B Gordon, Ivor Caro, Paul Kwon, Bruce E. Miller, Peter Compton, Craig L Leonardi
    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.

  • Safety of Efalizumab in adults with chronic moderate to severe plaque psoriasis: A phase IIIb, randomized, controlled trial
    International journal of dermatology, 2006
    Co-Authors: Kim Papp, Kenneth B Gordon, Ivor Caro, Patricia A. Walicke, Xiaolin Wang, Bernard S Goffe, Reni Bressinck, Scott Fretzin, Steven Kempers, Alan Menter
    Abstract:

    Background  To provide safety data for Efalizumab, a recombinant humanized monoclonal IgG1 antibody, in adults with chronic plaque psoriasis. Methods  A 12-week, Phase IIIb, randomized, double-blind, parallel-group, placebo-controlled trial. At 58 study sites in the USA and Canada, 686 patients with moderate to severe chronic plaque psoriasis received an initial conditioning dose of Efalizumab 0.7 mg/kg subcutaneously (SC) followed by either 11 weekly doses of Efalizumab 1 mg/kg SC or matching placebo. Main outcome measures were safety and tolerability outcomes (primary) and efficacy outcomes (secondary). Results  During 12 weeks of therapy with Efalizumab or placebo, the incidence of clinical adverse events was 82.2% and 72.9%, respectively; the incidence of serious adverse events was 1.8% and 3.4%, respectively; and the incidence of nonserious adverse events leading to withdrawal was 1.8% and 1.7%, respectively. In the Efalizumab group, there were no clinically significant changes in vital signs or laboratory parameters and no evidence of end-organ toxicities. A significantly higher proportion of patients receiving Efalizumab than those receiving placebo achieved ≥ 75% improvement in the Psoriasis Area and Severity Index (PASI) (P 

  • clinical efficacy of Efalizumab in patients with chronic plaque psoriasis results from three randomized placebo controlled phase iii trials part i
    Journal of Cutaneous Medicine and Surgery, 2005
    Co-Authors: David M. Pariser, Kim Papp, Kenneth B Gordon, Paul Kwon, Craig L Leonardi, Peter Compton, Patricia A. Walicke, Amy Chen Rundle, Mark Lebwohl
    Abstract:

    Effective psoriasis therapies are needed for long-term symptom control. Assess Efalizumab (Raptiva®) efficacy in a large cohort of psoriasis patients. 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. All efficacy measures reached statistical significance within each of the individual studies (p < 0.001) and overall. More Efalizumab-treated patients achieved ≥ 75% and ≥ 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. Efalizumab resulted in early and significant improvement for all efficacy endpoints and was well tolerated in patients with moderate to severe chronic plaque psoriasis.

Ivor Caro - One of the best experts on this subject based on the ideXlab platform.

  • Safety of Efalizumab Therapy in Patients with Moderate to Severe Psoriasis
    Drug Safety, 2008
    Co-Authors: Tiffani Hamilton, Ivor Caro, Peter Compton, Alan Menter, Jeffrey Sobell, Kim A Papp
    Abstract:

    Background: Psoriasis is a chronic autoimmune disease characterized by infiltration of the dermis and epidermis by activated T cells and the hyperproliferation and abnormal differentiation of keratinocytes. It is a life-long disease with alternating periods of remission and recurrence. Efalizumab is a humanized, recombinant, T-cell targeting monoclonal antibody, approved for use in adults with chronic moderate to severe plaque psoriasis. Objective: To assess the safety of continued or newly initiated treatment with Efalizumab for up to 48 weeks in patients with psoriasis who were treated previously with Efalizumab or placebo. Methods: This study was an open-label, 48-week extension of a previously published 12-week, randomized, double-blind, parallel-group, placebo-controlled, multicentre, phase IIIb study, carried out in the US and Canada between 24 October 2002 and 2 July 2004. Patients were followed and treated at the study clinic in an outpatient setting and also were trained to self-administer the drug at home. Patients comprising individuals with chronic moderate to severe plaque psoriasis who had completed the 12-week, placebo-controlled segment of the study were eligible for enrolment in the extension phase. Of the 686 patients enrolled in the study, 636 (92.7%) enrolled in the open-label extension of the study, 418 of whom had received 12 weeks of Efalizumab therapy and 218 of whom had received 12 weeks of placebo. All patients entering the open-label phase of the study received Efalizumab 1 mg/kg/wk for an additional 48 weeks, for a maximum exposure of up to 60 weeks. Safety was evaluated by an assessment of adverse events, including infections and serious adverse events. Results: The rate of withdrawal due to adverse events remained low throughout the trial, ranging from 1.2% to 6.6% during the 12-week segments of the open-label extension phase of the trial. The incidence of adverse events decreased with increased exposure to Efalizumab; the incidence during the initial 12 weeks of exposure to Efalizumab was 79.0% compared with 72.9% for patients exposed to placebo. Patients treated with Efalizumab for 13–24 weeks, 25–36 weeks, 37–8 weeks and 49–60 weeks experienced adverse events at an incidence of 66.8%, 54.3%, 49.6% and 48.5%, respectively. The incidence of serious adverse events ranged from 1.6% to 3.5% during the 12-week segments of Efalizumab therapy, compared with an incidence of 3.4% for placebo-treated patients. The incidence of infection ranged from 9.9% to 14.7% during the 12-week segments of Efalizumab therapy, compared with an incidence of 19.1% for placebo-treated patients. Malignancies were reported with an incidence of ≤1.0% for Efalizumab-treated patients during any 12-week segment compared with 0.4% for the 12-week placebo-treated patients. Of the 15 malignancies reported for Efalizumab-treated patients, 13 were basal cell (n = 4) or squamous cell (n = 9) carcinomas. Conclusions: These results support the short-term safety profile demonstrated for Efalizumab over a longer-term therapy period of up to 60 weeks.

  • Efalizumab : results of a 3-year continuous dosing study for the long-term control of psoriasis
    The British journal of dermatology, 2008
    Co-Authors: Craig L Leonardi, Ivor Caro, Alan Menter, Tiffani K. Hamilton, B. Xing, Alice B. Gottlieb
    Abstract:

    Summary Background  Efalizumab, a T-cell-targeted, recombinant, humanized, monoclonal IgG1 antibody, inhibits key T-cell-mediated steps in the pathogenesis of psoriasis. Efalizumab is approved for the treatment of moderate-to-severe chronic plaque psoriasis in adults in more than 50 countries. Objectives  To evaluate the efficacy and safety of long-term, continuous Efalizumab therapy in patients with psoriasis. Methods  This open-label, multicentre phase III study enrolled 339 patients with moderate-to-severe chronic plaque psoriasis. During the initial 3-month phase, patients received subcutaneous Efalizumab 2 mg kg−1 weekly with randomization to receive concomitant fluocinolone acetonide or placebo ointment during month 3. The second phase was a long-term observational period; patients achieving a ≥ 50% improvement in the Psoriasis Area and Severity Index (PASI) score were eligible to receive Efalizumab 1 mg kg−1 weekly for up to 33 months. The final 3-month treatment period was an optional transition period for patients who completed the 33-month segment before Efalizumab became commercially available. Results  After 3 months, 41·3% of patients achieved a ≥ 75% improvement in PASI (PASI-75) and 13·0% achieved a ≥ 90% improvement (PASI-90). Continued improvement was observed: 45·4% and 24·5% achieved PASI-75 and PASI-90, respectively, at the end of the observational phase. The safety profile was stable, with no new or no increase in common events over 36 months of treatment. Conclusions  This was the longest continuous study using a biologic therapy for psoriasis. Clinical benefit of Efalizumab improved over the first 18 months and was maintained during 36 months of continuous therapy. Long-term Efalizumab therapy is appropriate for many patients with plaque psoriasis.

  • Efalizumab for the Treatment of Psoriatic Arthritis
    Journal of cutaneous medicine and surgery, 2007
    Co-Authors: Kim Papp, Ivor Caro, Hoi M. Leung, Marvin Garovoy, Philip J. Mease
    Abstract:

    Background:Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. Efalizumab, a T cell-targeted, recombinant human monoclonal antibody, is approved for the treatment of adult patients with chronic moderate to severe plaque psoriasis. The effect of Efalizumab therapy on PsA has not previously been investigated.Objective:This phase II randomized, double-blind, placebo-controlled multicenter study evaluated the efficacy and safety of Efalizumab for the treatment of PsA.Methods:Patients were required to be on at least one of the following concomitant systemic therapies for PsA: nonsteroidal anti-inflammatory drugs, corticosteroids, and/or sulfasalazine or methotrexate. One hundred fifteen patients with active PsA were enrolled and randomized in the study. Of these, 107 were treated weekly with Efalizumab 1 mg/kg or placebo for 12 weeks, followed by 12 additional weeks of open-label Efalizumab.Results:At week 12, 28% of Efalizumab-treated patients achieved ACR-20 response (a 20% redu...

  • safety of Efalizumab in adults with chronic moderate to severe plaque psoriasis a phase iiib randomized controlled trial
    International Journal of Dermatology, 2006
    Co-Authors: Kim Papp, Kenneth B Gordon, Ivor Caro, Patricia A. Walicke, Xiaolin Wang, Bernard S Goffe, Reni Bressinck, Scott Fretzin, Steven Kempers, Alan Menter
    Abstract:

    Background  To provide safety data for Efalizumab, a recombinant humanized monoclonal IgG1 antibody, in adults with chronic plaque psoriasis. Methods  A 12-week, Phase IIIb, randomized, double-blind, parallel-group, placebo-controlled trial. At 58 study sites in the USA and Canada, 686 patients with moderate to severe chronic plaque psoriasis received an initial conditioning dose of Efalizumab 0.7 mg/kg subcutaneously (SC) followed by either 11 weekly doses of Efalizumab 1 mg/kg SC or matching placebo. Main outcome measures were safety and tolerability outcomes (primary) and efficacy outcomes (secondary). Results  During 12 weeks of therapy with Efalizumab or placebo, the incidence of clinical adverse events was 82.2% and 72.9%, respectively; the incidence of serious adverse events was 1.8% and 3.4%, respectively; and the incidence of nonserious adverse events leading to withdrawal was 1.8% and 1.7%, respectively. In the Efalizumab group, there were no clinically significant changes in vital signs or laboratory parameters and no evidence of end-organ toxicities. A significantly higher proportion of patients receiving Efalizumab than those receiving placebo achieved ≥ 75% improvement in the Psoriasis Area and Severity Index (PASI) (P < 0.001), ≥ 50% improvement in PASI (P < 0.001), and a static Physician's Global Assessment rating of Minimal or Clear (P < 0.001). The mean improvement in the Psoriasis Symptom Assessment was significantly greater in the Efalizumab group (P < 0.001). Conclusions  Efalizumab treatment SC for 12 weeks was safe, well tolerated, and effective in patients with moderate to severe chronic plaque psoriasis.

  • Efalizumab retreatment in patients with moderate to severe chronic plaque psoriasis.
    Journal of the American Academy of Dermatology, 2006
    Co-Authors: Kim A Papp, Bruce Miller, Kenneth B Gordon, Ivor Caro, Paul Kwon, Peter G Compton, Craig L Leonardi
    Abstract:

    Efalizumab targets T cell-mediated steps important in psoriasis immunopathogenesis. We sought to evaluate the efficacy and safety of Efalizumab retreatment in patients with moderate to severe plaque psoriasis. 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. 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. 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. These results suggest that retreatment with Efalizumab therapy is an efficacious option for patients who have previously discontinued treatment.

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  • Monitoring patients treated with Efalizumab or alefacept.
    Current problems in dermatology, 2009
    Co-Authors: Kim Papp
    Abstract:

    Though alefacept and Efalizumab do not have robust development for treating inflammatory disorders other than psoriasis, they provided important therapeutic options for patients with chronic plaque psoriasis. Alefacept is administered in 12-week cycles and requires routine monitoring of CD4 lymphocyte counts as apoptosis of memory T cells is a hallmark of its mechanisms of action. In contrast, it is recommended to conduct monthly complete blood counts for patients on Efalizumab during the first few months of therapy; Efalizumab is intended for continuous long-term therapy. Alefacept works extremely well for a smaller cohort of patients. We cannot yet predetermine those who will respond through many cycles of alefacept. Efalizumab works extremely well for approxi-mately 40% of subjects, and possibly more when retreatment options are considered. Most important for patients on either therapy is appropriate intermittent clinical evaluations to ensure stable, safe, and effective therapy.

  • Long-term efficacy of up to 15 months' Efalizumab therapy in patients with moderate-to-severe chronic plaque psoriasis.
    Dermatologic Therapy, 2008
    Co-Authors: Darryl Toth, Kim Papp, David Gratton
    Abstract:

    The efficacy and safety of Efalizumab in the treatment of moderate-to-severe chronic psoriasis has been established in studies of up to 3 years' duration. This study aims to describe the efficacy of up to 15 months' treatment with Efalizumab and the convenience of therapy in patients with moderate-to-severe chronic plaque psoriasis. Patients who had completed a 3-month, double-blind, randomized, placebo-controlled, Phase IIIb trial entered a 12-month extension study and received Efalizumab, 1 mg/kg/week administered subcutaneously, for up to 12 months. Of 450 patients originally randomly assigned to receive Efalizumab, 40.9% achieved a reduction of > or = 75% in the Psoriasis Area and Severity Index score after 15 months of treatment. Improvements were also observed on the frequency and severity subscales of the Psoriasis Symptom Assessment. The majority of patients reported that Efalizumab treatment was more or much more convenient than other psoriasis treatments. Efalizumab, 1 mg/kg/week, provides long-term efficacy and good convenience with up to 15 months of continuous treatment.

  • Efalizumab for the Treatment of Psoriatic Arthritis
    Journal of cutaneous medicine and surgery, 2007
    Co-Authors: Kim Papp, Ivor Caro, Hoi M. Leung, Marvin Garovoy, Philip J. Mease
    Abstract:

    Background:Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. Efalizumab, a T cell-targeted, recombinant human monoclonal antibody, is approved for the treatment of adult patients with chronic moderate to severe plaque psoriasis. The effect of Efalizumab therapy on PsA has not previously been investigated.Objective:This phase II randomized, double-blind, placebo-controlled multicenter study evaluated the efficacy and safety of Efalizumab for the treatment of PsA.Methods:Patients were required to be on at least one of the following concomitant systemic therapies for PsA: nonsteroidal anti-inflammatory drugs, corticosteroids, and/or sulfasalazine or methotrexate. One hundred fifteen patients with active PsA were enrolled and randomized in the study. Of these, 107 were treated weekly with Efalizumab 1 mg/kg or placebo for 12 weeks, followed by 12 additional weeks of open-label Efalizumab.Results:At week 12, 28% of Efalizumab-treated patients achieved ACR-20 response (a 20% redu...

  • Approaches to discontinuing Efalizumab: an open-label study of therapies for managing inflammatory recurrence
    BMC dermatology, 2006
    Co-Authors: Kim Papp, Darryl Toth, Les Rosoph
    Abstract:

    Background Efalizumab is a humanised recombinant monoclonal IgG1 antibody for the treatment of moderate-to-severe plaque psoriasis. When treatment discontinuation is necessary, however, some patients may experience inflammatory recurrence of the disease, which can progress to rebound if untreated. This analysis evaluated approaches for managing inflammatory recurrence after discontinuation of Efalizumab.

  • safety of Efalizumab in adults with chronic moderate to severe plaque psoriasis a phase iiib randomized controlled trial
    International Journal of Dermatology, 2006
    Co-Authors: Kim Papp, Kenneth B Gordon, Ivor Caro, Patricia A. Walicke, Xiaolin Wang, Bernard S Goffe, Reni Bressinck, Scott Fretzin, Steven Kempers, Alan Menter
    Abstract:

    Background  To provide safety data for Efalizumab, a recombinant humanized monoclonal IgG1 antibody, in adults with chronic plaque psoriasis. Methods  A 12-week, Phase IIIb, randomized, double-blind, parallel-group, placebo-controlled trial. At 58 study sites in the USA and Canada, 686 patients with moderate to severe chronic plaque psoriasis received an initial conditioning dose of Efalizumab 0.7 mg/kg subcutaneously (SC) followed by either 11 weekly doses of Efalizumab 1 mg/kg SC or matching placebo. Main outcome measures were safety and tolerability outcomes (primary) and efficacy outcomes (secondary). Results  During 12 weeks of therapy with Efalizumab or placebo, the incidence of clinical adverse events was 82.2% and 72.9%, respectively; the incidence of serious adverse events was 1.8% and 3.4%, respectively; and the incidence of nonserious adverse events leading to withdrawal was 1.8% and 1.7%, respectively. In the Efalizumab group, there were no clinically significant changes in vital signs or laboratory parameters and no evidence of end-organ toxicities. A significantly higher proportion of patients receiving Efalizumab than those receiving placebo achieved ≥ 75% improvement in the Psoriasis Area and Severity Index (PASI) (P < 0.001), ≥ 50% improvement in PASI (P < 0.001), and a static Physician's Global Assessment rating of Minimal or Clear (P < 0.001). The mean improvement in the Psoriasis Symptom Assessment was significantly greater in the Efalizumab group (P < 0.001). Conclusions  Efalizumab treatment SC for 12 weeks was safe, well tolerated, and effective in patients with moderate to severe chronic plaque psoriasis.