Pharmacokinetics, Efficacy, and Safety of Upadacitinib in Pediatric Patients With Polyarticular-Course Juvenile Idiopathic Arthritis: An Interim Analysis of an Open-Label, Phase 1 Trial.

Objective: This work aimed to evaluate the pharmacokinetics, efficacy, and safety of upadacitinib, an oral selective JAK inhibitor, in pediatric patients with polyarticular-course juvenile idiopathic arthritis (pcJIA).

Methods: In an open-label, phase 1 study (SELECT-YOUTH), enrolled patients, aged 2 to <18 years with pcJIA, received body weight-based upadacitinib doses using a twice-daily oral solution or once-daily extended-release tablet based on their body weight and ability to swallow tablets. The study included a 7-day pharmacokinetic assessment, followed by a long-term efficacy and safety evaluation for up to 156 weeks, including an additional long-term safety cohort.

Pharmacokinetics, Safety, Tolerability, and Exploratory Efficacy of Upadacitinib in Children with Severe Atopic Dermatitis.

Purpose: This study aims to characterize the pharmacokinetics, safety, tolerability, and exploratory efficacy of upadacitinib, an oral Janus kinase inhibitor approved for treating moderate to severe atopic dermatitis (AD) in adults and adolescents, in children with severe AD.

Methods: In an open-label, multiple-dose, Phase 1 study, pediatric patients with severe AD from two age groups (2 to <6 years and 6 to <12 years) received bodyweight-based dosing regimens of upadacitinib using either twice-daily immediate-release (IR) oral solution or once-daily extended-release (ER) tablets. A pharmacokinetic assessment was conducted on Day 7 of the study, which was followed by a long-term safety and exploratory efficacy evaluation for up to 108 weeks.

Less Invasive Surfactant Administration: A Review of Current Evidence of Clinical Outcomes With Beractant.

Evidence supporting clinical recommendations or approval for less invasive surfactant administration (LISA) has primarily examined heterogeneous or small-volume (e.g., 1.

Direct comparison of risankizumab and fumaric acid esters in systemic therapy-naïve patients with moderate-to-severe plaque psoriasis: a randomized controlled trial.

Background: Fumaric acid esters (FAEs; Fumaderm ) are the most frequently prescribed first-line systemic treatment for moderate-to-severe plaque psoriasis in Germany. Risankizumab (Skyrizi ) is a humanized IgG1 monoclonal antibody that specifically binds to the p19 subunit of interleukin 23.

Objectives: To compare risankizumab treatment to FAEs in patients with psoriasis.

Patient-reported outcomes with risankizumab versus fumaric acid esters in systemic therapy-naïve patients with moderate to severe plaque psoriasis: a phase 3 clinical trial.

Background: In a phase 3 clinical study, patients from Germany with moderate to severe psoriasis who were naïve to systemic treatment and received risankizumab had greater and more rapid disease improvements compared with those who received fumaric acid esters (FAEs).

Objective: To evaluate patient-reported outcomes (PROs) in patients treated with risankizumab compared with FAEs.

Methods: Adult patients were randomized 1:1 to receive either risankizumab 150 mg subcutaneous injections at weeks 0, 4 and 16 or FAEs (Fumaderm ) provided according to the prescribing label.

Beractant and poractant alfa in premature neonates with respiratory distress syndrome: a systematic review of real-world evidence studies and randomized controlled trials.

Findings from previous meta-analyses of randomized clinical trials (RCTs) in premature infants with respiratory distress syndrome (RDS) varied as to whether clinical outcomes differed by type of animal-derived pulmonary surfactant; real-world evidence (RWE) was excluded. We extracted study characteristics and outcomes from full-text articles from a systematic search for studies that compared beractant with poractant alfa for RDS in preterm infants. RWE data were tabulated; RCT data were subjected to meta-analyses.

Efficacy and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir with low-dose ribavirin in patients with chronic hepatitis C virus genotype 1a infection without cirrhosis.

Patients infected with hepatitis C virus (HCV) treated with interferon-free direct-acting antivirals may still require ribavirin. However, ribavirin is associated with adverse events that can limit its use. This open-label, multicentre, Phase 3 study evaluated the safety and efficacy of ombitasvir/paritaprevir/ritonavir + dasabuvir (OBV/PTV/r + DSV) with low-dose ribavirin for 12 weeks in genotype 1a-infected patients without cirrhosis.

On estimands and the analysis of adverse events in the presence of varying follow-up times within the benefit assessment of therapies.

The analysis of adverse events (AEs) is a key component in the assessment of a drug's safety profile. Inappropriate analysis methods may result in misleading conclusions about a therapy's safety and consequently its benefit-risk ratio. The statistical analysis of AEs is complicated by the fact that the follow-up times can vary between the patients included in a clinical trial.

Efficacy and safety of adalimumab every other week versus methotrexate once weekly in children and adolescents with severe chronic plaque psoriasis: a randomised, double-blind, phase 3 trial.

Background: Adalimumab is indicated for the treatment of moderate to severe psoriasis in adults. We assessed the efficacy and safety of adalimumab in children and adolescents with severe plaque psoriasis.

Methods: This randomised, double-blind, multiperiod, phase 3 trial was done at 38 clinics in 13 countries.

Randomized Crossover Comparison of Injection Site Pain with 40 mg/0.4 or 0.8 mL Formulations of Adalimumab in Patients with Rheumatoid Arthritis.

Introduction: Adalimumab, an anti-tumor necrosis factor antibody, is currently available in a 40 mg/0.8 mL formulation. The objective of this analysis was to evaluate injection site-related pain, safety, and tolerability of a 40 mg/0.

Predictors of RSV LRTI Hospitalization in Infants Born at 33 to 35 Weeks Gestational Age: A Large Multinational Study (PONI).

Background: Preterm infants are at high risk of developing respiratory syncytial virus (RSV)-associated lower respiratory tract infection (LRTI). This observational epidemiologic study evaluated RSV disease burden and risk factors for RSV-associated LRTI hospitalization in preterm infants 33 weeks+0 days to 35 weeks+6 days gestational age not receiving RSV prophylaxis.

Methods: Preterm infants ≤6 months of age during RSV season (1 October 2013-30 April 2014) were followed at 72 sites across 23 countries from September 2013-July 2014 (study period).

Reduction in C-Reactive-Protein Levels With Adalimumab Therapy in Patients With Moderate-to-Severe Hand and/or Foot Psoriasis.

Introduction: We evaluated post hoc the relationship between Humira (adalimumab) therapy and high-sensitivity C-reactive protein (hs-CRP) levels in patients with moderate-to-severe hand and/or foot psoriasis from the 16-week placebo-controlled period of REACH.


Methods: REACH was a phase 4, multicenter, randomized, double-blind trial, evaluating adalimumab treatment for patients with psoriasis of the hands and/or feet. Adults were randomized 2:1 to adalimumab 40 mg every other week (following 80 mg at week 0) or matching placebo from weeks 1 to 16, followed by a 12-week, open-label extension.

Efficacy of Adalimumab Compared With Methotrexate or Placebo Stratified by Baseline BMI in a Randomized Placebo-Controlled Trial in Patients With Psoriasis.

Introduction: In the Comparative Study of Humira vs Methotrexate vs Placebo In Psoriasis Patients (CHAMPION) study, significantly more patients achieved ≥75% improvement in the Psoriasis Area and Severity Index (PASI75) and ≥90% improvement (PASI90) after 16 weeks of treatment with adalimumab (80 mg at week 0, then 40 mg every other week starting at week 1) compared with methotrexate (up to 25 mg/week orally) or placebo. In this exploratory analysis, the efficacy of adalimumab was evaluated in a subset of the CHAMPION patient population stratified by baseline body mass index (BMI).

Methods: PASI responses and Dermatology Life Quality Index (DLQI) scores through 16 weeks of treatment were examined by baseline BMI category (<25 kg/m2 [normal], 25 to <30 kg/m2 [overweight], and ≥30 kg/m2 [obese]) in patients with psoriasis with a baseline PASI total score ≥12.

A Randomized, Double-Blind, Placebo-Controlled Multicenter Study of Adalimumab in Pediatric Patients With Enthesitis-Related Arthritis.

Objective: Enthesitis-related arthritis (ERA) is a juvenile idiopathic arthritis (JIA) category, primarily affecting entheses and peripheral joints. This study evaluated efficacy, safety, and pharmacokinetics of adalimumab versus placebo in patients with ERA.

Methods: This is a phase III, multicenter, randomized double-blind study in patients ages ≥6 to <18 years with ERA treated with adalimumab (24 mg/m(2) , maximum dose 40 mg every other week) or placebo for 12 weeks, followed by up to 192 weeks of open-label adalimumab.

Adalimumab for the treatment of moderate to severe psoriasis: subanalysis of effects on scalp and nails in the BELIEVE study.

Background/objective: This post hoc analysis examined the effects of adalimumab in patients with scalp and/or nail psoriasis from BELIEVE (a randomized, controlled, multicentre phase 3 safety and efficacy trial).

Methods: Efficacy was assessed in the pooled treatment group (adalimumab with or without calcipotriol plus betamethasone dipropionate) by Psoriasis Area and Severity Index (75% improvement; PASI 75), Psoriasis Scalp Severity Index (PSSI), Nail Psoriasis Severity Index (NAPSI), Dermatology Life Quality Index (DLQI) and a visual analog scale (VAS) for pain.

Results: Of the 730 enrolled patients, 663 (91.

Safety and effectiveness of adalimumab in patients with rheumatoid arthritis over 5 years of therapy in a phase 3b and subsequent postmarketing observational study.

Introduction: Patients with active rheumatoid arthritis who had failed at least one disease-modifying anti-rheumatic drug (DMARD) were treated with adalimumab (ADA) in the ReAct study with the option to continue treatment for 5 years in ReAlise. The purpose of this study was to evaluate the long-term safety and effectiveness of ADA as prescribed from the first injection in ReAct to the last observation in ReAlise.

Methods: Patients received ADA alone or in combination with DMARDs according to usual clinical care practices.

Efficacy of adalimumab across subgroups of patients with moderate-to-severe chronic plaque psoriasis of the hands and/or feet: post hoc analysis of REACH.

Background: The Randomized Controlled Evaluation of Adalimumab in Treatment of Chronic Plaque Psoriasis of the Hands and Feet (REACH) trial demonstrated that adalimumab was efficacious and well-tolerated for the treatment of hand and/or foot psoriasis through 28 weeks.

Objective: To evaluate the effects of patient baseline characteristics on efficacy of adalimumab treatment of hand and/or foot psoriasis.

Methods: Patients with moderate-to-severe chronic plaque psoriasis of the hands and/or feet were randomized 2 : 1 to adalimumab or placebo during the 16 week, double-blind period of REACH.

Influence of psoriatic arthritis on the efficacy of adalimumab and on the treatment response of other markers of psoriasis burden: subanalysis of the BELIEVE study.

Background: Adalimumab is a fully human anti-TNF monoclonal antibody with demonstrated efficacy and safety in patients with moderate to severe psoriasis and psoriatic arthritis (PsA).

Objective: This study examined the effect of PsA on adalimumab treatment response in patients from the Phase IIIb BELIEVE trial (NCT00574249, ClinicalTrials.gov registry), and response of other markers of disease burden to adalimumab treatment.

A 52-week trial comparing briakinumab with methotrexate in patients with psoriasis.

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).

Relationship between methotrexate dosing and clinical response in patients with moderate to severe psoriasis: subanalysis of the CHAMPION study.

Background: CHAMPION was a phase III trial that compared adalimumab with methotrexate and placebo for chronic plaque psoriasis.

Objectives: To determine the relationship between methotrexate dosing and improvement in psoriasis for patients in CHAMPION.

Methods: Methotrexate-treated patients in CHAMPION received step-up dosing to 15 mg per week during the first 8 weeks.

Efficacy and safety of adalimumab in patients with psoriasis previously treated with anti-tumour necrosis factor agents: subanalysis of BELIEVE.

Background: Few large clinical studies have evaluated whether switching tumour necrosis factor antagonists (anti-TNFs) is likely to improve psoriasis in patients with prior anti-TNF treatment.

Objective: The aim of this subanalysis of the BELIEVE study was to assess the efficacy and safety of adalimumab for psoriasis in patients with and without previous anti-TNF treatment.

Methods: The BELIEVE study enrolled patients with moderate to severe psoriasis and prior failure, intolerance or contraindication to ≥2 systemic therapies.

Adalimumab for treatment of moderate to severe chronic plaque psoriasis of the hands and feet: efficacy and safety results from REACH, a randomized, placebo-controlled, double-blind trial.

Objective: To determine the efficacy, safety, and sustainability of response to adalimumab therapy for moderate to severe chronic plaque psoriasis involving hands and/or feet.

Design: Sixteen-week, randomized, double-blind, placebo-controlled evaluation of adalimumab therapy for moderate to severe chronic plaque psoriasis involving the hands and/or feet with a 12-week open-label extension (Randomized Controlled Evaluation of Adalimumab in Treatment of Chronic Plaque Psoriasis of the Hands and Feet [REACH]).

Setting: Multicenter outpatient study in the United States and Canada.

A phase IIIb, multicentre, randomized, double-blind, vehicle-controlled study of the efficacy and safety of adalimumab with and without calcipotriol/betamethasone topical treatment in patients with moderate to severe psoriasis: the BELIEVE study.

Background: Data are lacking on the use of topical therapies in combination with tumour necrosis factor blockers for the treatment of psoriasis.

Objectives: To assess the efficacy and safety of adalimumab (ADA) with topical calcipotriol/betamethasone (C/B) in patients with psoriasis resembling those treated in routine clinical practice.

Methods: A 16-week, randomized, vehicle-controlled trial was conducted in patients with moderate to severe psoriasis and previous failure, intolerance or contraindications to two or more systemic treatments.