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David A. Williams - One of the best experts on this subject based on the ideXlab platform.

  • Effects of Briakinumab treatment for moderate to severe psoriasis on health-related quality of life and work productivity and activity impairment: results from a randomized phase III study.
    Journal of the European Academy of Dermatology and Venereology, 2013
    Co-Authors: Kim Papp, Murali Sundaram, Y. Bao, David A. Williams, James Signorovitch, Y. Wang, J.m. Valdes, Parvez Mulani
    Abstract:

    Background Psoriasis is known to have a significant negative impact on a patient's health-related quality of life, including social, recreational and work activities. Objective To evaluate the effects of Briakinumab on quality of life and work productivity measures in patients with moderate to severe psoriasis. Methods Patients received either Briakinumab (n = 981) or placebo (n = 484) during the 12-week induction phase of trial M06-890. At week 12, patients with a Physician's Global Assessment score of ‘Clear’ or ‘Minimal’ entered the 40-week maintenance phase and were to receive Briakinumab every 4 weeks, Briakinumab every 12 weeks, or placebo. At weeks 12 and 52, treatment groups were compared using mean change from baseline in health-related quality of life and Work Productivity and Activity Impairment Questionnaire scores and the percentage of patients with minimum clinically important differences. Results At week 12, more than half of the Briakinumab-treated patients achieved improvements meeting or exceeding minimum clinically important differences for Dermatology Life Quality Index (75.9%), and psoriasis- (64.8%), and psoriatic arthritis-related (54.1%) pain scores; 48.4% achieved improvements for activity impairment. Although improvements in quality of life and work productivity measures were maintained at week 52 for both Briakinumab regimens, responder rates were consistently greater in the every-4-week group than in the every-12-week group. Conclusion Briakinumab treatment resulted in clinically significant improvements in quality of life and work productivity in adults with moderate to severe psoriasis. Maintenance therapy was associated with a more pronounced benefit for the every-4-week Briakinumab regimen.

  • a phase iii randomized controlled trial of the fully human il 12 23 mab Briakinumab in moderate to severe psoriasis
    Journal of Investigative Dermatology, 2012
    Co-Authors: Kenneth B. Gordon, Kim Papp, David A. Williams, Richard G. Langley, Alice B. Gottlieb, Gerald G. Krueger, Bruce E. Strober, Joaquin Mario Valdes
    Abstract:

    A previous phase II trial demonstrated that the fully human anti-IL-12/23 mAb Briakinumab was efficacious in moderate-to-severe psoriasis. A subsequent 52-week, double-blind, placebo-controlled phase III study evaluated induction and maintenance treatment. Patients were randomized 2:1 to Briakinumab (200mg at weeks 0 and 4 and 100mg at week 8) or placebo; those with physician's global assessment "clear" or "minimal" (PGA "clear/minimal") at week 12 were then re-randomized 2:2:1 to Briakinumab 100 mg every 4 weeks (q4-wk), every 12 weeks (q12-wk), or to matching placebo to week 52. Primary analyses conducted by nonresponder imputation compared proportions achieving PGA "clear/minimal" (weeks 12 and 52) and ≥75% improvement in psoriasis area and severity index (PASI 75; week 12). In all, 76.0% of Briakinumab vs. 4.3% of placebo-treated patients achieved PGA "clear/minimal," and 80.7% vs. 4.5%, respectively, achieved PASI 75 at week 12 ( P P

  • A phase III, randomized, controlled trial of the fully human IL-12/23 mAb Briakinumab in moderate-to-severe psoriasis.
    Journal of Investigative Dermatology, 2012
    Co-Authors: Kenneth B. Gordon, Kim Papp, David A. Williams, Richard G. Langley, Alice B. Gottlieb, Gerald G. Krueger, Bruce E. Strober, Joaquin Mario Valdes
    Abstract:

    A previous phase II trial demonstrated that the fully human anti-IL-12/23 mAb Briakinumab was efficacious in moderate-to-severe psoriasis. A subsequent 52-week, double-blind, placebo-controlled phase III study evaluated induction and maintenance treatment. Patients were randomized 2:1 to Briakinumab (200mg at weeks 0 and 4 and 100mg at week 8) or placebo; those with physician's global assessment "clear" or "minimal" (PGA "clear/minimal") at week 12 were then re-randomized 2:2:1 to Briakinumab 100 mg every 4 weeks (q4-wk), every 12 weeks (q12-wk), or to matching placebo to week 52. Primary analyses conducted by nonresponder imputation compared proportions achieving PGA "clear/minimal" (weeks 12 and 52) and ≥75% improvement in psoriasis area and severity index (PASI 75; week 12). In all, 76.0% of Briakinumab vs. 4.3% of placebo-treated patients achieved PGA "clear/minimal," and 80.7% vs. 4.5%, respectively, achieved PASI 75 at week 12 ( P P

  • efficacy and safety results from a phase iii randomized controlled trial comparing the safety and efficacy of Briakinumab with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis
    British Journal of Dermatology, 2011
    Co-Authors: Bruce E. Strober, Jeffrey J Crowley, Paul S Yamauchi, M Olds, David A. Williams
    Abstract:

    Summary Background  The tumour necrosis factor-α antagonist etanercept and the interleukin (IL)-12/23p40 antagonist ustekinumab have been shown to be effective psoriasis therapies. The IL-12/23p40 antagonist Briakinumab was shown to be effective psoriasis treatment in a phase II study. Objectives  To assess the efficacy, safety and tolerability of Briakinumab compared with etanercept and placebo in patients with moderate to severe psoriasis. Methods  Three hundred and fifty patients were enrolled in this phase III, 12-week study (M10-315, NCT00710580) and randomized in the following 2:2:1 ratio: 139 patients received 200 mg Briakinumab at weeks 0 and 4 followed by 100 mg Briakinumab at week 8; 139 patients received 50 mg of etanercept twice weekly 3–4 days apart at weeks 0–11; 72 patients received placebo injections matching active treatment. The co-primary efficacy endpoints were the proportion of patients achieving a Physician’s Global Assessment (PGA) of 0/1 at week 12, and the proportion of patients achieving a Psoriasis Area and Severity Index (PASI) 75 response at week 12. Results  Of the Briakinumab-treated patients, 72·7% achieved a PGA of 0/1 at week 12 as compared with 29·5% of etanercept-treated patients and 4·2% of placebo-treated patients (P < 0·001, for both comparisons). Of the Briakinumab-treated patients, 80·6% achieved a PASI 75 response at week 12 as compared with 39·6% of etanercept-treated and 6·9% of placebo-treated patients (P < 0·001, for both comparisons). Serious adverse events were reported in two (1·4%) Briakinumab-treated patients, one (0·7%) etanercept-treated patient and two (2·8%) placebo-treated patients. Conclusions  In patients with moderate to severe psoriasis, Briakinumab had superior efficacy to both placebo and etanercept at 12 weeks as administered in this study.

  • efficacy and safety of Briakinumab vs etanercept and placebo in patients with moderate to severe chronic plaque psoriasis
    British Journal of Dermatology, 2011
    Co-Authors: Alice B. Gottlieb, M Olds, C Leonardi, Francisco A Kerdel, Stephanie L Mehlis, David A. Williams
    Abstract:

    Summary Background  The anti-interleukin-12/23p40 monoclonal antibody Briakinumab has been shown in a phase II study to be effective psoriasis treatment. Objectives  The aim of the current study was to assess the efficacy, safety and tolerability of Briakinumab compared with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis. Methods  In this phase III, 12-week study (M10-114, NCT00691964), 347 patients were randomized in a 2 : 2 : 1 ratio to receive 200 mg Briakinumab at weeks 0 and 4 followed by 100 mg Briakinumab at week 8 (n = 138); 50 mg of etanercept twice weekly 3–4 days apart at weeks 0–11 (n = 141); or placebo injections matching active treatment (n = 68). The co-primary efficacy endpoints were the proportion of patients achieving a Physician’s Global Assessment (PGA) of 0/1 at week 12, and the proportion of patients achieving a Psoriasis Area and Severity Index (PASI) 75 response at week 12. Results  Of the Briakinumab-treated patients, 71·0% achieved a PGA of 0/1 at week 12 as compared with 39·7% of etanercept-treated patients and 2·9% of placebo-treated patients, (P < 0·001, for both comparisons). Of the Briakinumab-treated patients 81·9% achieved a PASI 75 response at week 12 as compared with 56·0% of etanercept-treated and 7·4% of placebo-treated patients (P < 0·001, for both comparisons). Serious adverse event rates were reported in four (2·9%) patients receiving Briakinumab, one (0·7%) patient receiving etanercept and one (1·5%) placebo-treated patient. Conclusions  In patients with moderate to severe psoriasis, Briakinumab had superior efficacy to both placebo and etanercept at 12 weeks as administered in this study.

Joaquin Mario Valdes - One of the best experts on this subject based on the ideXlab platform.

  • Safety results from a pooled analysis of randomized, controlled phase II and III clinical trials and interim data from an open‐label extension trial of the interleukin‐12/23 monoclonal antibody, Briakinumab, in moderate to severe psoriasis
    Journal of the European Academy of Dermatology and Venereology : JEADV, 2012
    Co-Authors: Richard G. Langley, Kim Papp, Alice B. Gottlieb, Gerald G. Krueger, Kenneth B. Gordon, D. Williams, Joaquin Mario Valdes, C. Setze, Bruce E. Strober
    Abstract:

    Background  Anti-interleukin-12/23 treatment (anti-IL-12/23) has recently demonstrated significant efficacy for moderate to severe psoriasis, yet potential safety signals warrant further investigation. Objectives  Expand safety findings for the anti-IL-12/23, Briakinumab, beyond individual phase II and III clinical trials. Methods  Safety data pooled from five phase II and III clinical trials (parent studies) and an open-label extension study (OLE), through 22 October 2010; patients with ≥1 dose of Briakinumab in a parent study or the OLE are included. All parent study Briakinumab treatment groups were combined with the OLE population, which received 100-mg Briakinumab every 4 weeks. Adverse events (AEs) were collected from the first dose of Briakinumab, whether in a parent study or the OLE, through 45 days post-last dose. Results  Two thousand five hundred and twenty patients (4704 patient-years drug exposure) received ≥1 dose of Briakinumab during the interim period: 5.6% withdrew due to AEs. Serious infections occurred in 1.3% and malignancies in 2.6% (including 1.0% basal cell carcinoma, 0.8% squamous cell carcinoma). Twenty-seven major adverse cardiovascular events (MACE) occurred, seven in one parent study and 20 in the OLE (incidence = 0.57 events/100 PY). Four cardiovascular risk factors were retrospectively found to be significant predictors for MACE during Briakinumab exposure: history of cardiovascular disease, diabetes, body mass index (≥30) and baseline blood pressure (systolic ≥140 or diastolic ≥90). Conclusions  Pooled Briakinumab safety results from five parent studies and an OLE suggest increased rates of infections, malignancies and MACE, and that patients receiving anti-IL-12/23 treatment for moderate to severe psoriasis should be monitored for these potential safety signals.

  • a phase iii randomized controlled trial of the fully human il 12 23 mab Briakinumab in moderate to severe psoriasis
    Journal of Investigative Dermatology, 2012
    Co-Authors: Kenneth B. Gordon, Kim Papp, David A. Williams, Richard G. Langley, Alice B. Gottlieb, Gerald G. Krueger, Bruce E. Strober, Joaquin Mario Valdes
    Abstract:

    A previous phase II trial demonstrated that the fully human anti-IL-12/23 mAb Briakinumab was efficacious in moderate-to-severe psoriasis. A subsequent 52-week, double-blind, placebo-controlled phase III study evaluated induction and maintenance treatment. Patients were randomized 2:1 to Briakinumab (200mg at weeks 0 and 4 and 100mg at week 8) or placebo; those with physician's global assessment "clear" or "minimal" (PGA "clear/minimal") at week 12 were then re-randomized 2:2:1 to Briakinumab 100 mg every 4 weeks (q4-wk), every 12 weeks (q12-wk), or to matching placebo to week 52. Primary analyses conducted by nonresponder imputation compared proportions achieving PGA "clear/minimal" (weeks 12 and 52) and ≥75% improvement in psoriasis area and severity index (PASI 75; week 12). In all, 76.0% of Briakinumab vs. 4.3% of placebo-treated patients achieved PGA "clear/minimal," and 80.7% vs. 4.5%, respectively, achieved PASI 75 at week 12 ( P P

  • A phase III, randomized, controlled trial of the fully human IL-12/23 mAb Briakinumab in moderate-to-severe psoriasis.
    Journal of Investigative Dermatology, 2012
    Co-Authors: Kenneth B. Gordon, Kim Papp, David A. Williams, Richard G. Langley, Alice B. Gottlieb, Gerald G. Krueger, Bruce E. Strober, Joaquin Mario Valdes
    Abstract:

    A previous phase II trial demonstrated that the fully human anti-IL-12/23 mAb Briakinumab was efficacious in moderate-to-severe psoriasis. A subsequent 52-week, double-blind, placebo-controlled phase III study evaluated induction and maintenance treatment. Patients were randomized 2:1 to Briakinumab (200mg at weeks 0 and 4 and 100mg at week 8) or placebo; those with physician's global assessment "clear" or "minimal" (PGA "clear/minimal") at week 12 were then re-randomized 2:2:1 to Briakinumab 100 mg every 4 weeks (q4-wk), every 12 weeks (q12-wk), or to matching placebo to week 52. Primary analyses conducted by nonresponder imputation compared proportions achieving PGA "clear/minimal" (weeks 12 and 52) and ≥75% improvement in psoriasis area and severity index (PASI 75; week 12). In all, 76.0% of Briakinumab vs. 4.3% of placebo-treated patients achieved PGA "clear/minimal," and 80.7% vs. 4.5%, respectively, achieved PASI 75 at week 12 ( P P

  • A 52-Week Trial Comparing Briakinumab with Methotrexate in Patients with Psoriasis
    New England Journal of Medicine, 2011
    Co-Authors: Kristian Reich, Kim Papp, Richard G. Langley, Jeanpaul Ortonne, Kristina Unnebrink, Martin Kaul, Joaquin Mario Valdes
    Abstract:

    A B S T R AC T Background Briakinumab is a monoclonal antibody against the p40 molecule shared by interleukin-12 and interleukin-23, which is overexpressed in psoriatic skin lesions. We assessed the efficacy and safety of Briakinumab as compared with methotrexate in patients with psoriasis. Methods In this 52-week trial, we randomly assigned 317 patients with moderate-to-severe psoriasis to Briakinumab, at a dose of 200 mg at weeks 0 and 4 and 100 mg at week 8 and every 4 weeks thereafter (154 patients), or methotrexate, at a dose of 5 to 25 mg weekly (163 patients). The primary end points were the percentages of patients with at least 75% improvement in the score on the psoriasis area-and-severity index (PASI) at weeks 24 and 52 and a score on the physician’s global assessment of 0 (clear; i.e., no apparent disease) or 1 (minimal disease) at weeks 24 and 52. A total of 248 patients were enrolled in an ongoing 160-week open-label continuation study. Results At week 24, a total of 81.8% of the patients in the Briakinumab group versus 39.9% in the methotrexate group had at least 75% improvement in the PASI score, and 80.5% versus 34.4% had a score of 0 or 1 on the physician’s global assessment. The corre sponding percentages at week 52 were 66.2% versus 23.9% with at least a 75% improvement in the PASI score and 63.0% versus 20.2% with a score of 0 or 1 on the physician’s global assessment (P

  • a 52 week trial comparing Briakinumab with methotrexate in patients with psoriasis
    The New England Journal of Medicine, 2011
    Co-Authors: Kristian Reich, Kim Papp, Richard G. Langley, Jeanpaul Ortonne, Kristina Unnebrink, Martin Kaul, Joaquin Mario Valdes
    Abstract:

    A B S T R AC T Background Briakinumab is a monoclonal antibody against the p40 molecule shared by interleukin-12 and interleukin-23, which is overexpressed in psoriatic skin lesions. We assessed the efficacy and safety of Briakinumab as compared with methotrexate in patients with psoriasis. Methods In this 52-week trial, we randomly assigned 317 patients with moderate-to-severe psoriasis to Briakinumab, at a dose of 200 mg at weeks 0 and 4 and 100 mg at week 8 and every 4 weeks thereafter (154 patients), or methotrexate, at a dose of 5 to 25 mg weekly (163 patients). The primary end points were the percentages of patients with at least 75% improvement in the score on the psoriasis area-and-severity index (PASI) at weeks 24 and 52 and a score on the physician’s global assessment of 0 (clear; i.e., no apparent disease) or 1 (minimal disease) at weeks 24 and 52. A total of 248 patients were enrolled in an ongoing 160-week open-label continuation study. Results At week 24, a total of 81.8% of the patients in the Briakinumab group versus 39.9% in the methotrexate group had at least 75% improvement in the PASI score, and 80.5% versus 34.4% had a score of 0 or 1 on the physician’s global assessment. The corre sponding percentages at week 52 were 66.2% versus 23.9% with at least a 75% improvement in the PASI score and 63.0% versus 20.2% with a score of 0 or 1 on the physician’s global assessment (P<0.001 for all comparisons). During the 52-week study, serious adverse events occurred in 9.1% of the patients in the Briakinumab group (12.9 events per 100 patient-years) and in 6.1% in the methotrexate group (10.6 events per 100 patient-years). Serious infections occurred in 2.6% of the patients in the Briakinumab group (4.1 events per 100 patient-years) and in 1.8% in the methotrexate group (2.7 events per 100 patient-years); cancers occurred in 1.9% (2.0 events per 100 patient-years) versus 0%. Conclusions Briakinumab showed higher efficacy than methotrexate in patients with moderateto-severe psoriasis. Serious infections and cancers occurred more frequently with Briakinumab, but the differences were not significant. (Funded by Abbott Laboratories; ClinicalTrials.gov number, NCT00679731.)

Bruce E. Strober - One of the best experts on this subject based on the ideXlab platform.

  • Safety results from a pooled analysis of randomized, controlled phase II and III clinical trials and interim data from an open‐label extension trial of the interleukin‐12/23 monoclonal antibody, Briakinumab, in moderate to severe psoriasis
    Journal of the European Academy of Dermatology and Venereology : JEADV, 2012
    Co-Authors: Richard G. Langley, Kim Papp, Alice B. Gottlieb, Gerald G. Krueger, Kenneth B. Gordon, D. Williams, Joaquin Mario Valdes, C. Setze, Bruce E. Strober
    Abstract:

    Background  Anti-interleukin-12/23 treatment (anti-IL-12/23) has recently demonstrated significant efficacy for moderate to severe psoriasis, yet potential safety signals warrant further investigation. Objectives  Expand safety findings for the anti-IL-12/23, Briakinumab, beyond individual phase II and III clinical trials. Methods  Safety data pooled from five phase II and III clinical trials (parent studies) and an open-label extension study (OLE), through 22 October 2010; patients with ≥1 dose of Briakinumab in a parent study or the OLE are included. All parent study Briakinumab treatment groups were combined with the OLE population, which received 100-mg Briakinumab every 4 weeks. Adverse events (AEs) were collected from the first dose of Briakinumab, whether in a parent study or the OLE, through 45 days post-last dose. Results  Two thousand five hundred and twenty patients (4704 patient-years drug exposure) received ≥1 dose of Briakinumab during the interim period: 5.6% withdrew due to AEs. Serious infections occurred in 1.3% and malignancies in 2.6% (including 1.0% basal cell carcinoma, 0.8% squamous cell carcinoma). Twenty-seven major adverse cardiovascular events (MACE) occurred, seven in one parent study and 20 in the OLE (incidence = 0.57 events/100 PY). Four cardiovascular risk factors were retrospectively found to be significant predictors for MACE during Briakinumab exposure: history of cardiovascular disease, diabetes, body mass index (≥30) and baseline blood pressure (systolic ≥140 or diastolic ≥90). Conclusions  Pooled Briakinumab safety results from five parent studies and an OLE suggest increased rates of infections, malignancies and MACE, and that patients receiving anti-IL-12/23 treatment for moderate to severe psoriasis should be monitored for these potential safety signals.

  • a phase iii randomized controlled trial of the fully human il 12 23 mab Briakinumab in moderate to severe psoriasis
    Journal of Investigative Dermatology, 2012
    Co-Authors: Kenneth B. Gordon, Kim Papp, David A. Williams, Richard G. Langley, Alice B. Gottlieb, Gerald G. Krueger, Bruce E. Strober, Joaquin Mario Valdes
    Abstract:

    A previous phase II trial demonstrated that the fully human anti-IL-12/23 mAb Briakinumab was efficacious in moderate-to-severe psoriasis. A subsequent 52-week, double-blind, placebo-controlled phase III study evaluated induction and maintenance treatment. Patients were randomized 2:1 to Briakinumab (200mg at weeks 0 and 4 and 100mg at week 8) or placebo; those with physician's global assessment "clear" or "minimal" (PGA "clear/minimal") at week 12 were then re-randomized 2:2:1 to Briakinumab 100 mg every 4 weeks (q4-wk), every 12 weeks (q12-wk), or to matching placebo to week 52. Primary analyses conducted by nonresponder imputation compared proportions achieving PGA "clear/minimal" (weeks 12 and 52) and ≥75% improvement in psoriasis area and severity index (PASI 75; week 12). In all, 76.0% of Briakinumab vs. 4.3% of placebo-treated patients achieved PGA "clear/minimal," and 80.7% vs. 4.5%, respectively, achieved PASI 75 at week 12 ( P P

  • A phase III, randomized, controlled trial of the fully human IL-12/23 mAb Briakinumab in moderate-to-severe psoriasis.
    Journal of Investigative Dermatology, 2012
    Co-Authors: Kenneth B. Gordon, Kim Papp, David A. Williams, Richard G. Langley, Alice B. Gottlieb, Gerald G. Krueger, Bruce E. Strober, Joaquin Mario Valdes
    Abstract:

    A previous phase II trial demonstrated that the fully human anti-IL-12/23 mAb Briakinumab was efficacious in moderate-to-severe psoriasis. A subsequent 52-week, double-blind, placebo-controlled phase III study evaluated induction and maintenance treatment. Patients were randomized 2:1 to Briakinumab (200mg at weeks 0 and 4 and 100mg at week 8) or placebo; those with physician's global assessment "clear" or "minimal" (PGA "clear/minimal") at week 12 were then re-randomized 2:2:1 to Briakinumab 100 mg every 4 weeks (q4-wk), every 12 weeks (q12-wk), or to matching placebo to week 52. Primary analyses conducted by nonresponder imputation compared proportions achieving PGA "clear/minimal" (weeks 12 and 52) and ≥75% improvement in psoriasis area and severity index (PASI 75; week 12). In all, 76.0% of Briakinumab vs. 4.3% of placebo-treated patients achieved PGA "clear/minimal," and 80.7% vs. 4.5%, respectively, achieved PASI 75 at week 12 ( P P

  • efficacy and safety results from a phase iii randomized controlled trial comparing the safety and efficacy of Briakinumab with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis
    British Journal of Dermatology, 2011
    Co-Authors: Bruce E. Strober, Jeffrey J Crowley, Paul S Yamauchi, M Olds, David A. Williams
    Abstract:

    Summary Background  The tumour necrosis factor-α antagonist etanercept and the interleukin (IL)-12/23p40 antagonist ustekinumab have been shown to be effective psoriasis therapies. The IL-12/23p40 antagonist Briakinumab was shown to be effective psoriasis treatment in a phase II study. Objectives  To assess the efficacy, safety and tolerability of Briakinumab compared with etanercept and placebo in patients with moderate to severe psoriasis. Methods  Three hundred and fifty patients were enrolled in this phase III, 12-week study (M10-315, NCT00710580) and randomized in the following 2:2:1 ratio: 139 patients received 200 mg Briakinumab at weeks 0 and 4 followed by 100 mg Briakinumab at week 8; 139 patients received 50 mg of etanercept twice weekly 3–4 days apart at weeks 0–11; 72 patients received placebo injections matching active treatment. The co-primary efficacy endpoints were the proportion of patients achieving a Physician’s Global Assessment (PGA) of 0/1 at week 12, and the proportion of patients achieving a Psoriasis Area and Severity Index (PASI) 75 response at week 12. Results  Of the Briakinumab-treated patients, 72·7% achieved a PGA of 0/1 at week 12 as compared with 29·5% of etanercept-treated patients and 4·2% of placebo-treated patients (P < 0·001, for both comparisons). Of the Briakinumab-treated patients, 80·6% achieved a PASI 75 response at week 12 as compared with 39·6% of etanercept-treated and 6·9% of placebo-treated patients (P < 0·001, for both comparisons). Serious adverse events were reported in two (1·4%) Briakinumab-treated patients, one (0·7%) etanercept-treated patient and two (2·8%) placebo-treated patients. Conclusions  In patients with moderate to severe psoriasis, Briakinumab had superior efficacy to both placebo and etanercept at 12 weeks as administered in this study.

  • association between biologic therapies for chronic plaque psoriasis and cardiovascular events a meta analysis of randomized controlled trials
    JAMA, 2011
    Co-Authors: Caitriona Ryan, Richard G. Langley, Kenneth B. Gordon, Bruce E. Strober, Craig L Leonardi, James G Krueger, Alexa B Kimball, James A De Lemos, Yahya Daoud, Derek Blankenship
    Abstract:

    Context Ustekinumab and Briakinumab, monoclonal antibodies to the shared p40 subunit of interleukin (IL)-12 and IL-23, have shown efficacy in treating chronic plaque psoriasis (CPP). Preliminary reports of major adverse cardiovascular events (MACEs) in psoriasis patients receiving anti–IL-12/23 agents have prompted concern. Objective To evaluate a possible association between biologic therapies for CPP and MACEs via meta-analysis. Data Sources Randomized controlled trials (RCTs) of anti–IL-12/23 (ustekinumab and Briakinumab) agents and anti–tumor necrosis factor α (TNF-α) agents (adalimumab, etanercept, and infliximab) used in treating CPP were reviewed using the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Ovid MEDLINE from database inception to May 2011. The results of registered nonpublished completed studies were procured through abstract publications or poster presentations. Study Selection Randomized, placebo-controlled, double-blind, monotherapy studies (with safety outcome data for MACE) of IL-12/23 antibodies and anti–TNF-α agents in adults. Studies of psoriatic arthritis were excluded. Data Extraction Two investigators independently searched data while 6 investigators reviewed the abstracted data. Results A total of 22 RCTs comprising 10 183 patients met the predefined inclusion criteria. The primary outcome measure was MACE, a composite end point of myocardial infarction, cerebrovascular accident, or cardiovascular death during the placebo-controlled phase of treatment in patients receiving at least 1 dose of study agent or placebo. Absolute risk differences were used as an effect measure. There was no evidence of statistical heterogeneity across the studies using the I 2 statistic (I 2  = 0), allowing for combination of trial results using the Mantel-Haenszel fixed-effects method. During the placebo-controlled phases of the anti–IL-12/23 studies, 10 of 3179 patients receiving anti–IL-12/23 therapies experienced MACEs compared with zero events in 1474 patients receiving placebo (Mantel-Haenszel risk difference, 0.012 events/person-year; 95% confidence interval [CI], −0.001 to 0.026; P =.12). In the anti–TNF-α trials, only 1 of 3858 patients receiving anti–TNF-α agents experienced a MACE compared with 1 of 1812 patients receiving placebo (Mantel-Haenszel risk difference, −0.0005 events/person-year; 95% CI, −0.010 to 0.009; P = .94). Conclusions Compared with placebo, there was no significant difference in the rate of MACEs observed in patients receiving anti–IL-12/IL-23 antibodies or anti–TNF-α treatments. This study may have been underpowered to identify a significant difference.

Lidia Rudnicka - One of the best experts on this subject based on the ideXlab platform.

  • Briakinumab for the treatment of plaque psoriasis
    BioDrugs, 2012
    Co-Authors: Pawel Traczewski, Lidia Rudnicka
    Abstract:

    Psoriasis is a chronic inflammatory skin disorder affecting approximately 2% of individuals worldwide. An improved understanding of the pathogenesis of psoriasis has led to the development of targeted biologic therapies. Briakinumab (ABT-874) is a recombinant human antibody that blocks the biological activity of the cytokines interleukin (IL)-12 and IL-23 through their shared subunit p40. IL-12 and IL-23 are key mediators in T-cell differentiation and have been shown to play a significant role in maintaining inflammation and abnormal keratinocyte function in psoriasis patients through development and stimulation of Th1 and Th17 subsets, respectively. In one phase II and four phase III studies (including two 52-week trials), the Psoriasis Area and Severity Index (PASI)-75 score at weeks 12 and 52 was achieved by at least 80.6% and 66.2% (p<0.001) of patients receiving more than one dose of Briakinumab every 4 weeks, respectively, with high proportions of patients achieving PASI-90 and PASI-100 scores (at least 55.4% and 28.8%, respectively; p < 0.001). These studies indicate safety and tolerance of Briakinumab therapy for patients with moderate-to-severe chronic plaque psoriasis. In one clinical trial, therapy was associated with increased incidence of major cardiac events. Available results from two Briakinumab trials show its positive impact on health-related quality of life. However, the manufacturer has now withdrawn the application in the EU and US.

  • Briakinumab for the Treatment of Plaque Psoriasis
    BioDrugs, 2012
    Co-Authors: Pawel Traczewski, Lidia Rudnicka
    Abstract:

    Psoriasis is a chronic inflammatory skin disorder affecting approximately 2% of individuals worldwide. An improved understanding of the pathogenesis of psoriasis has led to the development of targeted biologic therapies. Briakinumab (ABT-874) is a recombinant human antibody that blocks the biological activity of the cytokines interleukin (IL)-12 and IL-23 through their shared subunit p40. IL-12 and IL-23 are key mediators in T-cell differentiation and have been shown to play a significant role in maintaining inflammation and abnormal keratinocyte function in psoriasis patients through development and stimulation of Th1 and Th17 subsets, respectively. In one phase II and four phase III studies (including two 52-week trials), the Psoriasis Area and Severity Index (PASI)-75 score at weeks 12 and 52 was achieved by at least 80.6% and 66.2% (p

  • New Interleukin-23 Pathway Inhibitors in Dermatology
    American Journal of Clinical Dermatology, 2011
    Co-Authors: Marta Kurzeja, Lidia Rudnicka, Malgorzata Olszewska
    Abstract:

    Interleukin (IL)-23 is an important regulator of T helper-17 lymphocytes, which influence the cutaneous immune system by production of IL-17 and several other proinflammatory cytokines. This pathway has been recently linked to the pathogenesis of psoriasis and numerous other skin diseases. A newly developed biologic drug, ustekinumab (CNTO-1275), which targets the p40 subunit of IL-12 and IL-23, was approved by the US FDA and the European Medicines Agency in 2009 for the treatment of moderate to severe psoriasis. Administered as subcutaneous injections of 45 mg at weeks 0 and 4, and then every 12 weeks, ustekinumab produces a 75% improvement in the Psoriasis Area and Severity Index (PASI) in 66.4–75.7% of patients and a Dermatology Life Quality Index (DLQI) score of 0 or 1 in 55–56% of patients after 12 weeks of therapy. A recent clinical trial also indicates the possible efficacy of ustekinumab in psoriatic arthritis. The proportion of patients who had at least one adverse event through 12 weeks in clinical studies was 51.6–57.6% in the ustekinumab group and 50.4% in the placebo group. Serious adverse events were observed in 1.4–1.6% of patients treated with ustekinumab and in 1.4% of patients receiving placebo. Injection-site reactions occurred in 1–2% of patients and 5% of patients developed anti-ustekinumab antibodies. Further studies are needed to evaluate the long-term efficacy and safety of ustekinumab. Another biologic drug that targets the same molecules, Briakinumab (ABT-874), has recently had its approval application withdrawn in the US and Europe to conduct further analysis and clinical trials. The company plans resubmission at a later date. Other IL-23 pathway inhibitors in the pipeline include anti-p19 monoclonal antibody and apilimod (STA-5326), which interfere with IL-23 activity, as well as secukinumab (AIN-457), LY-2439821, and AMG-827, which exhibit their activity at other targets of the IL-23 pathway.

  • New interleukin-23 pathway inhibitors in dermatology: ustekinumab, Briakinumab, and secukinumab.
    American Journal of Clinical Dermatology, 2011
    Co-Authors: Marta Kurzeja, Lidia Rudnicka, Malgorzata Olszewska
    Abstract:

    Interleukin (IL)-23 is an important regulator of T helper-17 lymphocytes, which influence the cutaneous immune system by production of IL-17 and several other proinflammatory cytokines. This pathway has been recently linked to the pathogenesis of psoriasis and numerous other skin diseases. A newly developed biologic drug, ustekinumab (CNTO-1275), which targets the p40 subunit of IL-12 and IL-23, was approved by the US FDA and the European Medicines Agency in 2009 for the treatment of moderate to severe psoriasis. Administered as subcutaneous injections of 45 mg at weeks 0 and 4, and then every 12 weeks, ustekinumab produces a 75% improvement in the Psoriasis Area and Severity Index (PASI) in 66.4–75.7% of patients and a Dermatology Life Quality Index (DLQI) score of 0 or 1 in 55–56% of patients after 12 weeks of therapy. A recent clinical trial also indicates the possible efficacy of ustekinumab in psoriatic arthritis.

Richard G. Langley - One of the best experts on this subject based on the ideXlab platform.

  • Safety results from a pooled analysis of randomized, controlled phase II and III clinical trials and interim data from an open‐label extension trial of the interleukin‐12/23 monoclonal antibody, Briakinumab, in moderate to severe psoriasis
    Journal of the European Academy of Dermatology and Venereology : JEADV, 2012
    Co-Authors: Richard G. Langley, Kim Papp, Alice B. Gottlieb, Gerald G. Krueger, Kenneth B. Gordon, D. Williams, Joaquin Mario Valdes, C. Setze, Bruce E. Strober
    Abstract:

    Background  Anti-interleukin-12/23 treatment (anti-IL-12/23) has recently demonstrated significant efficacy for moderate to severe psoriasis, yet potential safety signals warrant further investigation. Objectives  Expand safety findings for the anti-IL-12/23, Briakinumab, beyond individual phase II and III clinical trials. Methods  Safety data pooled from five phase II and III clinical trials (parent studies) and an open-label extension study (OLE), through 22 October 2010; patients with ≥1 dose of Briakinumab in a parent study or the OLE are included. All parent study Briakinumab treatment groups were combined with the OLE population, which received 100-mg Briakinumab every 4 weeks. Adverse events (AEs) were collected from the first dose of Briakinumab, whether in a parent study or the OLE, through 45 days post-last dose. Results  Two thousand five hundred and twenty patients (4704 patient-years drug exposure) received ≥1 dose of Briakinumab during the interim period: 5.6% withdrew due to AEs. Serious infections occurred in 1.3% and malignancies in 2.6% (including 1.0% basal cell carcinoma, 0.8% squamous cell carcinoma). Twenty-seven major adverse cardiovascular events (MACE) occurred, seven in one parent study and 20 in the OLE (incidence = 0.57 events/100 PY). Four cardiovascular risk factors were retrospectively found to be significant predictors for MACE during Briakinumab exposure: history of cardiovascular disease, diabetes, body mass index (≥30) and baseline blood pressure (systolic ≥140 or diastolic ≥90). Conclusions  Pooled Briakinumab safety results from five parent studies and an OLE suggest increased rates of infections, malignancies and MACE, and that patients receiving anti-IL-12/23 treatment for moderate to severe psoriasis should be monitored for these potential safety signals.

  • a phase iii randomized controlled trial of the fully human il 12 23 mab Briakinumab in moderate to severe psoriasis
    Journal of Investigative Dermatology, 2012
    Co-Authors: Kenneth B. Gordon, Kim Papp, David A. Williams, Richard G. Langley, Alice B. Gottlieb, Gerald G. Krueger, Bruce E. Strober, Joaquin Mario Valdes
    Abstract:

    A previous phase II trial demonstrated that the fully human anti-IL-12/23 mAb Briakinumab was efficacious in moderate-to-severe psoriasis. A subsequent 52-week, double-blind, placebo-controlled phase III study evaluated induction and maintenance treatment. Patients were randomized 2:1 to Briakinumab (200mg at weeks 0 and 4 and 100mg at week 8) or placebo; those with physician's global assessment "clear" or "minimal" (PGA "clear/minimal") at week 12 were then re-randomized 2:2:1 to Briakinumab 100 mg every 4 weeks (q4-wk), every 12 weeks (q12-wk), or to matching placebo to week 52. Primary analyses conducted by nonresponder imputation compared proportions achieving PGA "clear/minimal" (weeks 12 and 52) and ≥75% improvement in psoriasis area and severity index (PASI 75; week 12). In all, 76.0% of Briakinumab vs. 4.3% of placebo-treated patients achieved PGA "clear/minimal," and 80.7% vs. 4.5%, respectively, achieved PASI 75 at week 12 ( P P

  • A phase III, randomized, controlled trial of the fully human IL-12/23 mAb Briakinumab in moderate-to-severe psoriasis.
    Journal of Investigative Dermatology, 2012
    Co-Authors: Kenneth B. Gordon, Kim Papp, David A. Williams, Richard G. Langley, Alice B. Gottlieb, Gerald G. Krueger, Bruce E. Strober, Joaquin Mario Valdes
    Abstract:

    A previous phase II trial demonstrated that the fully human anti-IL-12/23 mAb Briakinumab was efficacious in moderate-to-severe psoriasis. A subsequent 52-week, double-blind, placebo-controlled phase III study evaluated induction and maintenance treatment. Patients were randomized 2:1 to Briakinumab (200mg at weeks 0 and 4 and 100mg at week 8) or placebo; those with physician's global assessment "clear" or "minimal" (PGA "clear/minimal") at week 12 were then re-randomized 2:2:1 to Briakinumab 100 mg every 4 weeks (q4-wk), every 12 weeks (q12-wk), or to matching placebo to week 52. Primary analyses conducted by nonresponder imputation compared proportions achieving PGA "clear/minimal" (weeks 12 and 52) and ≥75% improvement in psoriasis area and severity index (PASI 75; week 12). In all, 76.0% of Briakinumab vs. 4.3% of placebo-treated patients achieved PGA "clear/minimal," and 80.7% vs. 4.5%, respectively, achieved PASI 75 at week 12 ( P P

  • A 52-Week Trial Comparing Briakinumab with Methotrexate in Patients with Psoriasis
    New England Journal of Medicine, 2011
    Co-Authors: Kristian Reich, Kim Papp, Richard G. Langley, Jeanpaul Ortonne, Kristina Unnebrink, Martin Kaul, Joaquin Mario Valdes
    Abstract:

    A B S T R AC T Background Briakinumab is a monoclonal antibody against the p40 molecule shared by interleukin-12 and interleukin-23, which is overexpressed in psoriatic skin lesions. We assessed the efficacy and safety of Briakinumab as compared with methotrexate in patients with psoriasis. Methods In this 52-week trial, we randomly assigned 317 patients with moderate-to-severe psoriasis to Briakinumab, at a dose of 200 mg at weeks 0 and 4 and 100 mg at week 8 and every 4 weeks thereafter (154 patients), or methotrexate, at a dose of 5 to 25 mg weekly (163 patients). The primary end points were the percentages of patients with at least 75% improvement in the score on the psoriasis area-and-severity index (PASI) at weeks 24 and 52 and a score on the physician’s global assessment of 0 (clear; i.e., no apparent disease) or 1 (minimal disease) at weeks 24 and 52. A total of 248 patients were enrolled in an ongoing 160-week open-label continuation study. Results At week 24, a total of 81.8% of the patients in the Briakinumab group versus 39.9% in the methotrexate group had at least 75% improvement in the PASI score, and 80.5% versus 34.4% had a score of 0 or 1 on the physician’s global assessment. The corre sponding percentages at week 52 were 66.2% versus 23.9% with at least a 75% improvement in the PASI score and 63.0% versus 20.2% with a score of 0 or 1 on the physician’s global assessment (P

  • a 52 week trial comparing Briakinumab with methotrexate in patients with psoriasis
    The New England Journal of Medicine, 2011
    Co-Authors: Kristian Reich, Kim Papp, Richard G. Langley, Jeanpaul Ortonne, Kristina Unnebrink, Martin Kaul, Joaquin Mario Valdes
    Abstract:

    A B S T R AC T Background Briakinumab is a monoclonal antibody against the p40 molecule shared by interleukin-12 and interleukin-23, which is overexpressed in psoriatic skin lesions. We assessed the efficacy and safety of Briakinumab as compared with methotrexate in patients with psoriasis. Methods In this 52-week trial, we randomly assigned 317 patients with moderate-to-severe psoriasis to Briakinumab, at a dose of 200 mg at weeks 0 and 4 and 100 mg at week 8 and every 4 weeks thereafter (154 patients), or methotrexate, at a dose of 5 to 25 mg weekly (163 patients). The primary end points were the percentages of patients with at least 75% improvement in the score on the psoriasis area-and-severity index (PASI) at weeks 24 and 52 and a score on the physician’s global assessment of 0 (clear; i.e., no apparent disease) or 1 (minimal disease) at weeks 24 and 52. A total of 248 patients were enrolled in an ongoing 160-week open-label continuation study. Results At week 24, a total of 81.8% of the patients in the Briakinumab group versus 39.9% in the methotrexate group had at least 75% improvement in the PASI score, and 80.5% versus 34.4% had a score of 0 or 1 on the physician’s global assessment. The corre sponding percentages at week 52 were 66.2% versus 23.9% with at least a 75% improvement in the PASI score and 63.0% versus 20.2% with a score of 0 or 1 on the physician’s global assessment (P<0.001 for all comparisons). During the 52-week study, serious adverse events occurred in 9.1% of the patients in the Briakinumab group (12.9 events per 100 patient-years) and in 6.1% in the methotrexate group (10.6 events per 100 patient-years). Serious infections occurred in 2.6% of the patients in the Briakinumab group (4.1 events per 100 patient-years) and in 1.8% in the methotrexate group (2.7 events per 100 patient-years); cancers occurred in 1.9% (2.0 events per 100 patient-years) versus 0%. Conclusions Briakinumab showed higher efficacy than methotrexate in patients with moderateto-severe psoriasis. Serious infections and cancers occurred more frequently with Briakinumab, but the differences were not significant. (Funded by Abbott Laboratories; ClinicalTrials.gov number, NCT00679731.)