Safety of guselkumab in patients with moderate-to-severe psoriasis treated through 100 weeks: a pooled analysis from the randomized VOYAGE 1 and VOYAGE 2 studies.

Background: Long-term evaluation is required to confirm the safety profile of newer biologic agents.

Objectives: To report on pooled safety data from the ongoing VOYAGE 1 (NCT02207231) and VOYAGE 2 (NCT02207244) trials through 100 weeks of follow-up.

Methods: Patients were randomized to either guselkumab 100 mg at weeks 0 and 4 and every 8 weeks thereafter; placebo at weeks 0, 4, 12 followed by guselkumab 100 mg at weeks 16 and 20 and every 8 weeks thereafter; or adalimumab 80 mg at week 0, 40 mg at week 1, and 40 mg every 2 weeks thereafter.

Efficacy of Guselkumab Compared With Adalimumab and Placebo for Psoriasis in Specific Body Regions: A Secondary Analysis of 2 Randomized Clinical Trials.

Importance: Psoriasis of the scalp, palms and/or soles, and nails is challenging to treat.

Objective: To evaluate the effect of guselkumab on psoriasis in specific body regions.

Design, Setting, And Participants: VOYAGE 1 and VOYAGE 2 were, double-blind, placebo- and adalimumab-controlled studies of guselkumab conducted at 101 and 115 global sites, respectively, from November 3, 2014, to May 19, 2016.

Anxiety and depression in patients with moderate-to-severe psoriasis and comparison of change from baseline after treatment with guselkumab vs. adalimumab: results from the Phase 3 VOYAGE 2 study.

Background: Anxiety and depression are clinically significant comorbidities associated with psoriasis. Improvements in psoriasis are known to decrease anxiety and depression. Guselkumab, an anti-interleukin-23 monoclonal antibody, has demonstrated efficacy and safety for the treatment of moderate-to-severe psoriasis.

Patient-reported symptoms and signs of moderate-to-severe psoriasis treated with guselkumab or adalimumab: results from the randomized VOYAGE 1 trial.

Background: How patients experience the symptoms/signs of psoriasis is highly relevant for assessing treatment response.

Objectives: Compare outcomes with guselkumab, placebo and adalimumab utilizing the novel, validated Psoriasis Symptoms and Signs Diary (PSSD).

Methods: VOYAGE 1 is an ongoing, phase III, double-blinded, controlled trial of patients with moderate-to-severe psoriasis.

Population Pharmacokinetic Modeling of Guselkumab, a Human IgG1λ Monoclonal Antibody Targeting IL-23, in Patients with Moderate to Severe Plaque Psoriasis.

Psoriasis is a common inflammatory skin disorder that requires chronic treatment and is associated with multiple comorbidities. Guselkumab, a human immunoglobulin-G1-lambda monoclonal antibody, binds to interleukin-23 with high specificity and affinity and is effective in treating moderate to severe plaque psoriasis. As part of the guselkumab psoriasis clinical trial program, using a confirmatory approach, a population pharmacokinetics (PopPK) model was established using 13 014 PK samples from 1454 guselkumab-treated patients across 3 phase 2/3 trials.

Efficacy of guselkumab in subpopulations of patients with moderate-to-severe plaque psoriasis: a pooled analysis of the phase III VOYAGE 1 and VOYAGE 2 studies.

Background: Significant advances have been made in the treatment of moderate-to-severe plaque psoriasis with biological therapies; however, these agents may not work equally in all populations.

Objectives: To evaluate the efficacy of guselkumab in patient subgroups with moderate-to-severe psoriasis from the pooled guselkumab VOYAGE 1 and VOYAGE 2 phase III studies.

Methods: Using data from the pooled VOYAGE 1 and VOYAGE 2 psoriasis studies, analyses were performed to evaluate the consistency of efficacy [Investigator's Global Assessment (IGA) 0/1 (cleared or minimal psoriasis) and IGA 0 (cleared)] across subpopulations defined by demographics, baseline disease characteristics and previous psoriasis treatment.

Validation of psychometric properties and development of response criteria for the psoriasis symptoms and signs diary (PSSD): results from a phase 3 clinical trial.

Purpose: The Psoriasis Symptoms and Signs Diary (PSSD) is a patient-reported instrument that assesses severity of six symptoms (itch, skin tightness, burning, stinging, and pain) and five signs (dryness, cracking, scaling, shedding/flaking, redness, and bleeding) of psoriasis.

Materials And Methods: PSSD symptoms and signs summary scores (range, 0-100) were derived based on individual item scores (0-10 [absent-worst imaginable]). Using Psoriasis Area and Severity Index [PASI], Investigator's Global Assessment [IGA] and Dermatology Life Quality Index [DLQI]) data from the NAVIGATE trial of patients with moderate-to-severe psoriasis, analyses were conducted to further validate the PSSD (7-day recall version) and establish criteria for clinically meaningful improvements (CMIs).

Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double-blind, phase III NAVIGATE trial.

Background: Guselkumab, an anti-interleukin-23 monoclonal antibody, has demonstrated significant efficacy in phase III psoriasis trials.

Objectives: To evaluate the efficacy and safety of guselkumab in patients with moderate-to-severe plaque psoriasis who had an inadequate response to ustekinumab.

Methods: In this phase III, randomized, double-blind study, 871 patients received open-label ustekinumab (45 mg or 90 mg) at weeks 0 and 4.

Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial.

Background: Phase II data suggested that guselkumab, an anti-interleukin-23 monoclonal antibody, was efficacious in psoriasis.

Objective: We sought to assess efficacy and safety of guselkumab in moderate to severe psoriasis versus placebo and adalimumab, including interrupted treatment and switching adalimumab nonresponders to guselkumab.

Methods: Patients were randomized to guselkumab 100 mg (weeks 0 and 4, then every 8 weeks; n = 496); placebo→guselkumab (weeks 0, 4, and 12 then guselkumab at weeks 16 and 20; n = 248); or adalimumab (80 mg week 0, then 40 mg week 1, and every 2 weeks through week 23; n = 248).

Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: Results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial.

Background: Guselkumab, an interleukin-23 blocker, was superior to adalimumab in treating moderate to severe psoriasis in a phase II trial.

Objectives: We sought to compare efficacy and safety of guselkumab with adalimumab and placebo in patients with psoriasis treated for 1 year.

Methods: Patients were randomized to guselkumab 100 mg (weeks 0 and 4, then every 8 weeks; n = 329); placebo→guselkumab (weeks 0, 4, and 12 then guselkumab at weeks 16 and 20, then every 8 weeks; n = 174); or adalimumab (80 mg week 0, 40 mg week 1, then 40 mg every 2 weeks through week 47; n = 334).

A Phase 2 Trial of Guselkumab versus Adalimumab for Plaque Psoriasis.

Background: Little is known about the effect of specific anti-interleukin-23 therapy, as compared with established anti-tumor necrosis factor therapies, for the treatment of moderate-to-severe plaque psoriasis.

Methods: In a 52-week, phase 2, dose-ranging, randomized, double-blind, placebo-controlled, active-comparator trial, we compared guselkumab (CNTO 1959), an anti-interleukin-23 monoclonal antibody, with adalimumab in patients with moderate-to-severe plaque psoriasis. A total of 293 patients were randomly assigned to receive guselkumab (5 mg at weeks 0 and 4 and every 12 weeks thereafter, 15 mg every 8 weeks, 50 mg at weeks 0 and 4 and every 12 weeks thereafter, 100 mg every 8 weeks, or 200 mg at weeks 0 and 4 and every 12 weeks thereafter) through week 40, placebo, or adalimumab (standard dosage for psoriasis).

Long-term efficacy and safety of ustekinumab, with and without dosing adjustment, in patients with moderate-to-severe psoriasis: results from the PHOENIX 2 study through 5 years of follow-up.

Background: Evaluation of the dosing flexibility and long-term efficacy of biological agents is limited.

Objectives: To evaluate the long-term efficacy and safety of ustekinumab with and without dosing adjustment in the 5-year PHOENIX 2 study.

Methods: Patients were randomized to placebo or ustekinumab (45 or 90 mg) at weeks 0, 4, then every 12 weeks; patients receiving placebo crossed-over at week 12.

Information contributed by meta-analysis in exposure-response modeling: application to phase 2 dose selection of guselkumab in patients with moderate-to-severe psoriasis.

Ustekinumab, a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that binds with high affinity to human interleukin (IL)-12 and IL-23, has been approved to treat patients with psoriasis. Guselkumab is a related human IgG1 monoclonal antibody in clinical development which specifically blocks IL-23. The objective of this study was to study the exposure-response relationship of guselkumab to guide dose selection for a Phase 2 study in patients with moderate-to-severe psoriasis.

Guselkumab (an IL-23-specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis.

Background: IL-23 expression is increased in psoriatic lesions and might regulate TH17 T-cell counts in patients with psoriasis.

Objectives: We sought to test a novel IL-23-specific therapeutic agent for the treatment of psoriasis.

Methods: In this randomized, double-blind, placebo-controlled study the safety, tolerability, and clinical response of guselkumab, an anti-IL-23-specific mAb, were evaluated in patients with moderate-to-severe plaque psoriasis.

Ustekinumab improves nail disease in patients with moderate-to-severe psoriasis: results from PHOENIX 1.

Background: Most patients with psoriasis have nail changes, and treating nail psoriasis is challenging.

Objectives: To assess improvement in fingernail psoriasis with ustekinumab treatment in the PHOENIX 1 trial.

Methods: Patients received ustekinumab 45 mg or 90 mg, or placebo at weeks 0 and 4.

Two cases of hepatitis B in patients with moderate to severe psoriasis with ustekinumab.

Background: Patients with psoriasis who are treated with systemic and biologic therapies may have an increased risk of infections, including hepatitis B virus (HBV). Cytokines that modulate CD4+ T cell subsets, including interleukin (IL)-12 and IL-23, have been suggested to play a role in the pathogenesis of HBV infection.

Objective: To report the first known cases of acute HBV infection in 2 ustekinumab-treated patients with psoriasis from a phase 3 (PHOENIX 1) and a phase 4 (TRANSIT) study.

Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up.

Background: Long-term safety evaluations of biologics are needed to inform patient management decisions.

Objectives: To evaluate the safety of ustekinumab in patients with moderate-to-severe psoriasis treated for up to 5 years.

Methods: Safety data were pooled from four studies of ustekinumab for psoriasis.

Long-term efficacy of ustekinumab in patients with moderate-to-severe psoriasis treated for up to 5 years in the PHOENIX 1 study.

Background: Ongoing evaluation of biological agents in patients with moderate-to-severe psoriasis is needed to support their long-term use.

Objective: To evaluate long-term efficacy and safety of ustekinumab through 5 years in the PHOENIX 1 study.

Methods: Patients were randomized to placebo or ustekinumab (45 mg or 90 mg) at Weeks 0, 4 and every-12-weeks thereafter; placebo patients crossed-over to ustekinumab at Week 12.

The safety of ustekinumab treatment in patients with moderate-to-severe psoriasis and latent tuberculosis infection.

Background: Ustekinumab is a monoclonal antibody that targets interleukin (IL)-12/23 p40 to treat psoriasis. The IL-12 pathway is also important in regulating immunity to Mycobacterium tuberculosis.

Objectives: To evaluate the safety of isoniazid (INH) prophylaxis for newly identified latent tuberculosis infection (LTBI) in ustekinumab-treated patients with psoriasis.

An update on the long-term safety experience of ustekinumab: results from the psoriasis clinical development program with up to four years of follow-up.

Background: The efficacy and safety profile of ustekinumab with up to three years of exposure suggested a favorable benefit-risk profile in patients with moderate to severe psoriasis.

Objective: To evaluate the safety of ustekinumab in patients with moderate to severe psoriasis treated for up to four years.

Methods: Safety data were pooled across four Phase II/III randomized controlled trials.

Onset and duration of attenuation of exercise-induced bronchoconstriction in children by single-dose of montelukast.

Single-dose montelukast attenuates exercise-induced bronchoconstriction (EIB) in adults within 2 hours postdose and lasting through 24 hours. This study evaluated the onset and duration of EIB attenuation in children after a single dose of montelukast. A randomized, double-blind, placebo-controlled, two-period crossover study was performed.

The efficacy and tolerability of MK-0633, a 5-lipoxygenase inhibitor, in chronic asthma.

Leukotriene B4 (LTB(4)) is a potent inflammatory mediator in asthma, and is increased in more severe asthma. Targeting LTB(4), in addition to cysteinyl leukotrienes, could be beneficial in asthma. This was a randomized, double-blind trial of once-daily MK-0633, a potent 5-lypoxygenase inhibitor, 10 mg, 50 mg, and 100 mg, and placebo in patients 18-70 years with a history of chronic asthma, and FEV(1) ≥45 and ≤85% predicted.