A Randomized, Double-Blind, Placebo-Controlled Phase 2a Study of Tildrakizumab Efficacy and Safety in Patients With Active Ankylosing Spondylitis.

Objective: Tildrakizumab is an anti-interleukin-23p19 monoclonal antibody approved to treat moderate to severe plaque psoriasis. This study evaluated the efficacy and safety of tildrakizumab in patients with ankylosing spondylitis (AS).

Methods: In this randomized, double-blind, parallel-group, multinational trial ( clinicaltrials.

Tildrakizumab efficacy and safety in patients with psoriasis and concomitant metabolic syndrome: post hoc analysis of 5-year data from reSURFACE 1 and reSURFACE 2.

Background: Limited data are available on long-term efficacy and safety of biologics in patients with psoriasis and metabolic syndrome (MetS), a common comorbidity.

Objectives: This analysis updates tildrakizumab efficacy and safety for up to 5 years in patients with and without MetS.

Methods: This was a post hoc analysis of the double-blind, randomized, placebo-controlled, phase 3 reSURFACE 1 (NCT01722331) and reSURFACE 2 (NCT01729754) trials in adult patients with moderate to severe chronic plaque psoriasis.

Efficacy and safety of tildrakizumab in patients with active psoriatic arthritis: results of a randomised, double-blind, placebo-controlled, multiple-dose, 52-week phase IIb study.

Objectives: To evaluate efficacy and safety of the anti-interleukin-23p19 monoclonal antibody tildrakizumab in patients with psoriatic arthritis (PsA).

Methods: In this randomised, double-blind, placebo-controlled, phase IIb study, patients with active PsA were randomised 1:1:1:1:1 to tildrakizumab 200 mg every 4 weeks (Q4W); tildrakizumab 200, 100 or 20 mg Q12W; or placebo Q4W. Patients receiving tildrakizumab 20 mg or placebo switched to tildrakizumab 200 mg Q12W at W24; treatment continued to W52.

Five-year efficacy and safety of tildrakizumab in patients with moderate-to-severe psoriasis who respond at week 28: pooled analyses of two randomized phase III clinical trials (reSURFACE 1 and reSURFACE 2).

Background: The phase III reSURFACE 1 and reSURFACE 2 (NCT01722331/NCT01729754) trials of the anti-interleukin-23p19 monoclonal antibody tildrakizumab (TIL) for psoriasis treatment are complete.

Objectives: We present 5-year pooled data from reSURFACE 1 and reSURFACE 2.

Methods: reSURFACE 1 and reSURFACE 2 were double-blind, randomized, controlled studies with optional long-term extensions.

Long-term efficacy and safety of tildrakizumab in Japanese patients with moderate to severe plaque psoriasis: Results from a 5-year extension of a phase 3 study (reSURFACE 1).

The three part, double-blind, randomized, controlled reSURFACE 1 trial and extension study (NCT01722331) evaluated efficacy and safety of tildrakizumab in adults with moderate to severe plaque psoriasis. Patients with ≥50% improvement from baseline in Psoriasis Area and Severity Index (PASI 50) following treatment with tildrakizumab 100 mg (TIL100) or 200 mg (TIL200) could enter the optional long-term extension study and continue treatment at the same dose for an additional 192 weeks. This subgroup analysis assessed the long-term efficacy and safety of tildrakizumab treatment for Japanese patients enrolled in reSURFACE 1 for up to 5 years of treatment.

Tildrakizumab efficacy, drug survival, and safety are comparable in patients with psoriasis with and without metabolic syndrome: Long-term results from 2 phase 3 randomized controlled studies (reSURFACE 1 and reSURFACE 2).

Background: Data for the effect of metabolic syndrome (MetS) on the efficacy and safety of biologic agents for psoriasis treatment are limited.

Objective: To evaluate long-term tildrakizumab efficacy, drug survival, and safety in patients with psoriasis by baseline MetS status.

Methods: Post hoc analyses of up to 3 years of efficacy data and 5 years of safety data from the phase 3, double-blind, randomized controlled reSURFACE 1 and 2 trial (NCT01722331 and NCT01729754) base and extension studies were conducted for patients receiving continuous tildrakizumab 100 or 200 mg.

The Effect of Tildrakizumab on Cardiometabolic Risk Factors in Psoriasis by Metabolic Syndrome Status: Post Hoc Analysis of Two Phase 3 Trials (ReSURFACE 1 and ReSURFACE 2).

Background: Metabolic syndrome (MetS) is the most prevalent comorbidity in psoriasis and increases the risk of cardiovascular disease, diabetes, and mortality. Assessment of impacts of biologic therapies on cardiometabolic risk factors are relatively limited. This study evaluated the effect of tildrakizumab on cardiometabolic risk factors in patients with moderate to severe plaque psoriasis and stratified by MetS status.

Disease activity and treatment efficacy using patient-level Psoriasis Area and Severity Index scores from tildrakizumab phase 3 clinical trials.

Background: It is unclear whether primary efficacy outcomes in plaque psoriasis clinical trials represent residual disease during treatment.

Objectives: To evaluate supplementing dichotomous efficacy with residual disease activity.

Methods: This post hoc analysis used pooled, patient-level data after tildrakizumab 100 mg ( = 616) or placebo ( = 309) treatment from reSURFACE 1/2 (NCT01722331/NCT01729754) phase 3 clinical trials of patients with moderate to severe plaque psoriasis.

Efficacy of tildrakizumab by patient demographic and disease characteristics across a phase 2b and 2 phase 3 trials in patients with moderate-to-severe chronic plaque psoriasis.

Background: Tildrakizumab is a high-affinity, anti-interleukin-23p19 monoclonal antibody approved for treatment of moderate-to-severe plaque psoriasis.

Objectives: To evaluate the effects of patient demographic and disease characteristics on tildrakizumab efficacy using phase 2b/3 trial data.

Methods: Data from patients who received placebo, or tildrakizumab 100 or 200 mg, in P05495 [NCT01225731], reSURFACE 1 [NCT01722331] and reSURFACE 2 [NCT01729754] were analysed.

Sustained and continuously improved efficacy of tildrakizumab in patients with moderate-to-severe plaque psoriasis.

Tildrakizumab is a high-affinity, humanized, IgG1 κ, anti-interleukin-23 monoclonal antibody approved for moderate-to-severe plaque psoriasis. This analysis examined whether tildrakizumab's week-28 efficacy can be sustained or improved to week 52. Psoriasis patients on the same-dose tildrakizumab (100 or 200 mg) in the first 52 weeks achieving week-28 PASI ≥50 were pooled from two phase-3 randomized controlled trials, and grouped into four mutually exclusive week-28 PASI response groups.

Long-term efficacy and safety of tildrakizumab for moderate-to-severe psoriasis: pooled analyses of two randomized phase III clinical trials (reSURFACE 1 and reSURFACE 2) through 148 weeks.

Background: Tildrakizumab is a specific anti-interleukin-23p19 monoclonal antibody approved for the treatment of plaque psoriasis.

Objectives: To evaluate the long-term efficacy and safety of tildrakizumab treatment for patients with moderate-to-severe psoriasis for up to 148 weeks.

Methods: Pooled analysis from two double-blind, randomized controlled trials: reSURFACE 1 and reSURFACE 2.

An assessment of adalimumab efficacy in three Phase III clinical trials using the European Consensus Programme criteria for psoriasis treatment goals.

Background: The European Consensus Programme (ECP) established pan-European consensus definitions of psoriasis disease severity and treatment goals among 19 psoriasis experts from European nations.

Objectives: To use the ECP treatment goals to retrospectively assess adalimumab efficacy in patients who participated in Phase III clinical trials and met ECP criteria for moderate to severe psoriasis.

Methods: Three trials were analysed: CHAMPION (n = 108), REVEAL (n = 814) and BELIEVE (n = 364).

The long-term safety of adalimumab treatment in moderate to severe psoriasis: a comprehensive analysis of all adalimumab exposure in all clinical trials.

Background: A favorable benefit-risk profile has been established for adalimumab, with up to 5 years of treatment in 13 clinical trials in patients with moderate to severe chronic plaque psoriasis.

Objective: The aim of this analysis was to assess the long-term safety of all adalimumab exposure in all psoriasis clinical trials.

Methods: A total of six sets of data were analyzed as follows: (i) all cumulative safety data from all exposure for all adalimumab-treated patients in the 13 clinical trials in moderate to severe psoriasis (All Adalimumab Treatment Population) through April 2007, November 2008, and November 2009, respectively; (ii) longitudinal data for 1403 patients treated with adalimumab 40 mg every other week (eow) dosing (Every Other Week Population) through June 2007 and April 2010; and (iii) data from placebo-controlled periods of clinical trials.

Long-term efficacy and safety of adalimumab in patients with moderate to severe psoriasis treated continuously over 3 years: results from an open-label extension study for patients from REVEAL.

Background: REVEAL was a 52-week phase III trial of adalimumab therapy for moderate to severe chronic plaque psoriasis. Patients from REVEAL could enter an open-label extension trial to receive adalimumab for approximately 3 years of total therapy.

Objective: We sought to determine long-term efficacy and safety of continuous adalimumab therapy for patients from REVEAL.

Benefit-risk assessment of tumour necrosis factor antagonists in the treatment of psoriasis.

Background: Safety of tumour necrosis factor (TNF) antagonists is a primary concern for clinicians prescribing them to patients with psoriasis.

Objectives: To determine the benefit-risk balance of TNF antagonists in psoriasis.

Methods: Through integrated analyses of published literature, we calculated the number needed to treat (NNT) for various efficacy measures and the number needed to harm (NNH) for various adverse events for approved dosing regimens of adalimumab, etanercept and infliximab.

Development of murine lupus involves the combined genetic contribution of the SLAM and FcgammaR intervals within the Nba2 autoimmune susceptibility locus.

Autoantibodies are of central importance in the pathogenesis of Ab-mediated autoimmune disorders. The murine lupus susceptibility locus Nba2 on chromosome 1 and the syntenic human locus are associated with a loss of immune tolerance that leads to antinuclear Ab production. To identify gene intervals within Nba2 that control the development of autoantibody-producing B cells and to determine the cellular components through which Nba2 genes accomplish this, we generated congenic mice expressing various Nba2 intervals where genes for the FcgammaR, SLAM, and IFN-inducible families are encoded.

Homeostatically proliferating CD4 T cells are involved in the pathogenesis of an Omenn syndrome murine model.

Patients with Omenn syndrome (OS) have hypomorphic RAG mutations and develop varying manifestations of severe combined immunodeficiency. It is not known which symptoms are caused directly by the RAG mutations and which depend on other polymorphic genes. Our current understanding of OS is limited by the lack of an animal model.