Improving Diversity in a Novel Psoriasis Study: VISIBLE as a Framework for Clinical Trial Quality Improvement.

Importance: Diverse racial and ethnic representation in clinical trials has been limited, not representative of the US population, and the subject of pending US Food and Drug Administration guidance. Psoriasis presentation and disease burden can vary by skin pigmentation, race and ethnicity, and socioeconomic differences. Overall, there are limited primary data on clinical response, genetics, and quality of life in populations with psoriasis and skin of color (SoC).

Efficacy and safety of guselkumab in patients with active psoriatic arthritis who had inadequate efficacy and/or intolerance to one prior tumor necrosis factor inhibitor: study protocol for SOLSTICE, a phase 3B, multicenter, randomized, double-blind, placebo-controlled study.

Background: Tumor necrosis factor inhibitors (TNFi) are frequently chosen as the first biologic for patients with psoriatic arthritis (PsA). Given that many patients with PsA are TNFi inadequate responders (TNF-IR; either inadequate efficacy or intolerance), treatments utilizing alternative mechanisms of action are needed. In phase 3 studies, the fully human interleukin (IL)-23p19 subunit-inhibitor, guselkumab, was efficacious in patients with active PsA, including TNFi-IR.

Efficacy and safety of 48 weeks of guselkumab for patients with Crohn's disease: maintenance results from the phase 2, randomised, double-blind GALAXI-1 trial.

Background: Many patients with moderately to severely active Crohn's disease do not respond to available therapies or lose response over time. The GALAXI-1 study previously found that three intravenous guselkumab dosages showed superior clinical and endoscopic outcomes over placebo at week 12 in patients with moderately to severely active Crohn's disease. We report the safety and efficacy of subcutaneous guselkumab maintenance regimens to week 48 in the GALAXI-1 study.

Long-Term Safety of Guselkumab in Patients with Psoriatic Disease: An Integrated Analysis of Eleven Phase II/III Clinical Studies in Psoriasis and Psoriatic Arthritis.

Introduction: The benefit/risk profiles of biologics can be affected by comorbidities, certain demographic characteristics, and concomitant medications; therefore, it is important to evaluate the long-term safety profiles of biologics across broad patient populations. Guselkumab was well tolerated and efficacious across individual pivotal clinical studies in adults with moderate-to-severe psoriasis and/or active psoriatic arthritis (PsA).

Objectives: The objective of the current analysis was to evaluate guselkumab safety in a large population of patients with psoriatic disease by pooling adverse event (AE) data from 11 phase II/III studies (seven in psoriasis; four in PsA).

A clinical review of structural damage in psoriatic arthritis for dermatologists: From pathogenesis to ongoing controversies.

Psoriatic arthritis (PsA) is a chronic inflammatory disease that often goes unrecognized in patients with psoriasis. As a result, patients may develop significant structural damage before diagnosis and initiation of adequate treatment. Dermatologists are in an unique position to identify early signs and symptoms of PsA.

Guselkumab for the Treatment of Crohn's Disease: Induction Results From the Phase 2 GALAXI-1 Study.

Background & Aims: Guselkumab, a selective p19 interleukin-23 antagonist, is approved for the treatment of plaque psoriasis and psoriatic arthritis. This study evaluated the efficacy and safety of guselkumab in patients with moderately to severely active Crohn's disease with inadequate response or intolerance to conventional or biologic therapy.

Methods: GALAXI-1, a phase 2, double-blind, placebo-controlled study, randomized patients 1:1:1:1:1 to intravenous guselkumab 200 mg, 600 mg, or 1200 mg at weeks 0, 4, and 8; intravenous ustekinumab approximately 6 mg/kg at week 0 and 90 mg subcutaneously at week 8; or placebo.

Maintenance Golimumab Treatment in Pediatric UC Patients With Moderately to Severely Active UC: PURSUIT PEDS PK Long-Term Study Results.

Background: Long-term safety, pharmacokinetics, and efficacy of open-label golimumab therapy in children with moderate-severe ulcerative colitis were evaluated.

Methods: Week-6 golimumab responders (Mayo score decrease of ≥30% and ≥3 points from baseline, rectal bleeding subscore of 0/1 or ≥1 decrease from baseline) entered the long-term extension at week 14 and received maintenance therapy (subcutaneous, q4w). Patients ≥45 kg could receive at-home treatments at week 18.

Effects of Ustekinumab on Histologic Disease Activity in Patients With Crohn's Disease.

Background & Aims: Although ustekinumab is an effective therapy for moderate to severe Crohn's disease (CD), its effects on the microscopic manifestations of CD are unknown.

Methods: We evaluated the effects of ustekinumab on histologic CD activity in an analysis of data from 251 participants in phase 3 induction and maintenance studies. Two endoscopic biopsy samples were collected at weeks 0, 8, and 44 from the ileum, splenic flexure, and rectum (18 biopsy samples from each patient).

Population Pharmacokinetics and Exposure-Response Modeling Analyses of Golimumab in Children With Moderately to Severely Active Ulcerative Colitis.

Population pharmacokinetics (PK) and exposure-response (E-R) analyses were conducted to compare the PK and E-R relationships of golimumab between children and adults with ulcerative colitis. PK data following subcutaneous golimumab administration to children with ulcerative colitis (6-17 years) in the PURSUIT-PEDS-PK study, adults with ulcerative colitis in the PURSUIT study, and children with pediatric polyarticular juvenile idiopathic arthritis (2-17 years) in the GO-KIDS study, were included in the population PK analysis. E-R analysis was conducted using logistic regression to link serum golimumab concentration and Mayo score-based efficacy outcomes in pediatric and adult ulcerative colitis.

Efficacy of Ustekinumab for Inducing Endoscopic Healing in Patients With Crohn's Disease.

Background & Aims: We evaluated the ability of ustekinumab, a monoclonal antibody against the p40 subunit of interleukins 12 and 23, to induce endoscopic healing in patients with moderate to severe Crohn's disease (CD).

Methods: We performed an endoscopy substudy of 334 patients with moderate to severe CD participating in 3 randomized controlled phase 3 studies to determine the safety and efficacy of ustekinumab induction and maintenance therapy. All patients underwent colonoscopy at baseline and week 8 of the induction studies and at week 44 of the maintenance study; all colonoscopies were assessed by a blinded central reader.

Molecular Comparison of Adult and Pediatric Ulcerative Colitis Indicates Broad Similarity of Molecular Pathways in Disease Tissue.

Background: Efficacy data from adult ulcerative colitis (UC) clinical trials are often extrapolated for pediatric prescribing. Consequently, it is important to understand similarities/differences in pediatric and adult UC. Pediatric UC tends to have more extensive disease at presentation, yet genetic studies have not detected pathways that distinguish the populations, and differences in mucosal gene expression between adult and pediatric UC are not well characterized.

Subcutaneous Golimumab in Pediatric Ulcerative Colitis: Pharmacokinetics and Clinical Benefit.

Background: Current treatments for pediatric ulcerative colitis (UC) are limited. We evaluated the pharmacokinetics and clinical benefits of subcutaneous golimumab, an anti-tumor necrosis factor agent, in moderately-to-severely active pediatric patients with UC refractory to conventional therapy.

Methods: We report a multicenter, open-label study of golimumab with a pharmacokinetics phase (week 0-14).

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.

Efficacy and safety of ustekinumab in Chinese patients with moderate to severe plaque-type psoriasis: results from a phase 3 clinical trial (LOTUS).

Background: Available biologic agents for the treatment of psoriasis in China are limited.

Objectives: The LOTUS study is a phase 3, double-blind, placebo-controlled study that evaluated the efficacy and safety of ustekinumab in Chinese patients with moderate to severe plaque-type psoriasis.

Patients And Methods: Patients (n=322) were randomized to receive ustekinumab 45 mg or placebo at weeks 0 and 4, with placebo crossover to ustekinumab at week 12; all patients were followed up to week 36.

Evaluating practice patterns for managing moderate to severe plaque psoriasis: role of the family physician.

Objective: To describe practice patterns for care of Canadian patients with moderate to severe plaque psoriasis.

Design: Online survey of a consumer panel.

Setting: Participants were drawn from a population-wide Canadian consumer database.

A Canadian online survey to evaluate awareness and treatment satisfaction in individuals with moderate to severe plaque psoriasis.

Background: Psoriasis is a chronic inflammatory disease associated with comorbidities and decreased quality of life. This survey is aimed to better understand the impact of disease on Canadian patients, and to examine awareness and use of available treatment options.

Methods: An online survey was conducted using a consumer panel.

Invulnerability and the intention to drink and drive: an application of the theory of planned behavior.

The present study aims at an examination, based on the theory of planned behavior (TPB), of the psychological antecedents of young Chinese people's intentions to drive after drinking. One hundred and twenty-four licensed drivers (aged from 19 to 35 years) successfully completed an online questionnaire. Using path analysis, we found the most proximal predictors of intention to be attitudes and perceived behavioral control, whereas invulnerability as well as subjective norms indirectly influenced intention by promoting favorable attitudes toward and greater perceived behavioral control over driving after alcohol use.

A Canadian self-administered online survey to evaluate the impact of moderate-to-severe psoriasis among patients.

Background: Few population studies of individuals living with psoriasis have been performed in Canada.

Objective: The objective of this survey was to understand the severity and impact of psoriasis on the lives of Canadian patients.

Methods: An online survey was conducted using a consumer panel.

The human severe acute respiratory syndrome coronavirus (SARS-CoV) 8b protein is distinct from its counterpart in animal SARS-CoV and down-regulates the expression of the envelope protein in infected cells.

The severe acute respiratory syndrome coronavirus (SARS-CoV), isolated from humans infected during the peak of epidemic, encodes two accessory proteins termed as 8a and 8b. Interestingly, the SARS-CoV isolated from animals contains an extra 29-nucleotide in this region such that these proteins are fused to become a single protein, 8ab. Here, we compared the cellular properties of the 8a, 8b and 8ab proteins by examining their cellular localizations and their abilities to interact with other SARS-CoV proteins.

Chronic prenatal ethanol exposure and increased concentration of fatty acid ethyl esters in meconium of term fetal Guinea pig.

In humans, the occurrence of prenatal exposure to ethanol is difficult to validate objectively. Increased concentration of fatty acid ethyl esters (FAEE) in the meconium of the newborn may be a biomarker of prenatal ethanol exposure. The validity of this proposed biomarker was tested in pregnant guinea pigs that received chronic oral administration of 4 g ethanol/kg maternal body weight/day (n=8), isocaloric-sucrose/pair-feeding (n=8) or water (n=2) throughout gestation.

Serum equol, bone mineral density and biomechanical bone strength differ among four mouse strains.

The extent of conversion of daidzein to its metabolite, equol, by intestinal microflora may be a critical step that determines if a diet rich in daidzein protects against the deterioration of bone after estrogen withdrawal. The objective was to determine the extent that daidzein is converted to equol. In addition, bone mineral content (BMC), bone mineral density (BMD) and strength of femurs and lumbar vertebrae (LV) in four mouse strains were measured.