Stereotactic body radiation therapy and thermal ablation for treatment of NSCLC: A systematic literature review and meta-analysis.

Rationale: Stereotactic body radiation therapy (SBRT) is the standard of care for inoperable early stage non-small cell lung cancer (NSCLC). Use of image guided thermal ablation (IGTA; including microwave ablation [MWA] and radiofrequency ablation [RFA]) has increased in NSCLC, however there are no studies comparing all three.

Objective: To compare the efficacy of IGTA (including MWA and RFA) and SBRT for the treatment of NSCLC.

The Effect of Definitions and Cancer Prevalence on Diagnostic Yield Estimates of Bronchoscopy: A Simulation-based Analysis.

Studies of bronchoscopy have reported diagnostic yield (DY) using different calculation methods, which has hindered comparisons across studies. To quantify the effect of the variability of four methods on DY estimates of bronchoscopy. We performed a simulation-based analysis of patients undergoing bronchoscopy using variations around base case assumptions for cancer prevalence (60%), distribution of nonmalignant findings, and degree of follow-up information at a fixed sensitivity of bronchoscopy for malignancy (80%).

Novel Image-Guided Flexible-Probe Transbronchial Microwave Ablation for Stage 1 Lung Cancer.

Background: Image-guided percutaneous thermal ablation is an established treatment option for early-stage lung cancer in medically inoperable patients but carries a high risk of pleura-related complications, particularly pneumothorax.

Objective: This study aimed to determine if image-guided transbronchial microwave ablation (tMWA) is a feasible approach to treat peripheral stage 1 lung cancer.

Method: A prospective, single-arm, multicenter study sought to enroll 40 adults who were medically inoperable or declined surgery for peripheral stage 1 lung tumors (≤20 mm).

Complications After Transthoracic Needle Biopsy of Pulmonary Nodules: A Population-Level Retrospective Cohort Analysis.

Objective: To provide recent population-based estimates of transthoracic needle biopsy (TTNB) complications and risk factors associated with these complications.

Methods: This retrospective cohort analysis included adults from a nationally representative longitudinal insurance claims data set who underwent TTNB in 2017 or 2018. Complications that were evaluated included pneumothorax, hemorrhage, and air embolism.

Ustekinumab Pharmacokinetics and Exposure Response in a Phase 3 Randomized Trial of Patients With Ulcerative Colitis.

Background & Aims: The efficacy of antibody-based therapeutics depends on their pharmacokinetics. The pharmacokinetic and exposure response profiles of ustekinumab, a monoclonal antibody against interleukin 12/interleukin 23, are known in patients with Crohn's disease, yet there are few data from patients with ulcerative colitis. We characterized ustekinumab's pharmacokinetics, exposure response, and optimal serum concentrations in patients with ulcerative colitis.

Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis.

Background: The efficacy of ustekinumab, an antagonist of the p40 subunit of interleukin-12 and interleukin-23, as induction and maintenance therapy in patients with ulcerative colitis is unknown.

Methods: We evaluated ustekinumab as 8-week induction therapy and 44-week maintenance therapy in patients with moderate-to-severe ulcerative colitis. A total of 961 patients were randomly assigned to receive an intravenous induction dose of ustekinumab (either 130 mg [320 patients] or a weight-range-based dose that approximated 6 mg per kilogram of body weight [322]) or placebo (319).

Peficitinib, an Oral Janus Kinase Inhibitor, in Moderate-to-severe Ulcerative Colitis: Results From a Randomised, Phase 2 Study.

Background And Aims: Janus kinase [JAK] inhibitors have shown efficacy in ulcerative colitis [UC]. We studied the dose-response, efficacy, and safety of peficitinib, an oral JAK inhibitor, in patients with moderate-to-severe UC.

Methods: In this Phase 2b, dose-ranging trial, we evaluated peficitinib at 25 mg once daily [o.

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.

The Effects of Ustekinumab on Health-related Quality of Life in Patients With Moderate to Severe Crohn's Disease.

Background And Aims: We assessed the effect of ustekinumab on health-related quality of life [HRQOL] in adults with Crohn's disease [CD].

Methods: Patients with moderately to severely active CD and inadequate response or intolerance to tumour necrosis factor antagonists [UNITI-1, n = 741], or conventional therapy [UNITI-2, n = 627] were randomised to placebo, ustekinumab 130 mg, or 6 mg/kg intravenous induction therapy. At Week 8, ustekinumab-treated responders (Crohn's Disease Activity Index [CDAI] reduction ≥100 or CDAI <150 points) were re-randomised to subcutaneous maintenance therapy [IM-UNITI, n = 388] with placebo, ustekinumab 90 mg every 12 weeks [q12w], or ustekinumab 90 mg every 8 weeks [q8w], for 44 additional weeks.

Pharmacokinetics and Exposure Response Relationships of Ustekinumab in Patients With Crohn's Disease.

Background & Aims: Ustekinumab is a monoclonal antibody that binds with high affinity to the p40 subunit of human interleukin 12 (IL12 and IL23) that has been approved for treatment of patients with moderate to severe Crohn's disease (CD). However, there are few data on its pharmacokinetic properties or the relationship between drug exposure levels and patient response. We collected data from 2 Phase 3 induction studies and 1 maintenance study to determine ustekinumab's pharmacokinetic features, relationship between exposure and response, and optimal serum concentrations for efficacy.

Evaluation of Risk of Major Adverse Cardiovascular Events With Biologic Therapy in Patients With Psoriasis.

Background: Psoriasis is associated with increased risk of major adverse cardiovascular events (MACE).

Objectives: Compare MACE risk with biologics vs topical/phototherapy use.

Methods: Psoriasis Longitudinal Assessment Registry (PSOLAR) is an international psoriasis registry of patients eligible to receive biologic/systemic treatments prospectively.

Challenges in longitudinal exposure-response modeling of data from complex study designs: a case study of modeling CDAI score for ustekinumab in patients with Crohn's disease.

Informative exposure-response modeling of clinical endpoints is important in drug development to identify optimum dose and dosing regimens. Despite much recent progress in mechanism-based longitudinal modeling of clinical data, challenges remain in clinical trials of diseases such as Crohn's disease, where a commonly used composite endpoint Crohn's Disease Activity Index (CDAI) has considerable variation in its administration and scoring between different assessors and complex study designs typically include maintenance phases with randomized withdrawal re-randomizations and other response driven dose adjustments. This manuscript illustrates the complexities of exposure-response modeling of such composite endpoint data through a latent-variable based Indirect Response model framework for CDAI scores using data from three phase III trials of ustekinumab in patients with moderate-to-severe Crohn's Disease.

First-in-human study to assess guselkumab (anti-IL-23 mAb) pharmacokinetics/safety in healthy subjects and patients with moderate-to-severe psoriasis.

Purpose: The purpose of this study is to evaluate the pharmacokinetics, immunogenicity, safety, and tolerability of guselkumab, a human monoclonal antibody with high affinity and specificity for binding to interleukin-23.

Methods: In this first-in-human, phase 1, randomized study, a single intravenous (IV; 0.03-10 mg/kg) or subcutaneous (SC; 10-300 mg) dose of guselkumab was administered to 47 healthy subjects, and a single SC dose (placebo, 10, 30, 100, 300 mg) was administered to 24 patients with moderate-to-severe psoriasis.

HLA-C*06:02 Allele and Response to IL-12/23 Inhibition: Results from the Ustekinumab Phase 3 Psoriasis Program.

Several small studies suggest that the presence of the human leukocyte antigen (HLA)-Cw6 (C*06:02) allele may be a predictor of improved response to ustekinumab. This study was designed to assess the association of the HLA-C*06:02 allele with response to ustekinumab in large cohorts of patients from the phase 3 studies of ustekinumab in moderate-to-severe psoriasis. In this retrospective study, both HLA-C*06:02-positive and -negative patients demonstrated good responses to ustekinumab (86% vs.

Ustekinumab in adolescent patients age 12 to 17 years with moderate-to-severe plaque psoriasis: results of the randomized phase 3 CADMUS study.

Background: Safe and effective therapies are needed for pediatric patients with psoriasis.

Objective: The purpose of this study was to evaluate ustekinumab in patients age 12 to 17 years who had moderate-to-severe psoriasis.

Methods: Patients (n = 110) were randomly assigned to ustekinumab standard dosing (SD; 0.

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.

Latent variable indirect response joint modeling of a continuous and a categorical clinical endpoint.

Informative exposure-response modeling of clinical endpoints is important in drug development. There has been much recent progress in latent variable modeling of ordered categorical endpoints, including the application of indirect response (IDR) models and accounting for residual correlations between multiple categorical endpoints. This manuscript describes a framework of latent-variable-based IDR models that facilitate easy simultaneous modeling of a continuous and a categorical clinical endpoint.

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.

Immune response to pneumococcus and tetanus toxoid in patients with moderate-to-severe psoriasis following long-term ustekinumab use.

Background: Little is known about the impact of long-term use of immunosuppressive agents on immune response.

Objectives: Assess the impact of continuous maintenance ustekinumab treatment on patients' ability to mount immune responses to pneumococcal (T-cell-independent) and tetanus toxoid (T-cell-dependent) vaccines.

Patients And Methods: Ustekinumab-treated patients with moderate-to-severe psoriasis treated in the long-term extension of the Phase 3 PHOENIX 2 trial (n=60) were compared with control psoriasis patients not receiving systemic therapy (n=56).

Modulation of cardiometabolic pathways in skin and serum from patients with psoriasis.

Background: Moderate-to-severe psoriasis is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD); however, the link is poorly understood.

Methods: Skin and serum from patients with psoriasis were evaluated to understand if there was evidence of dysregulation in a targeted group of inflammatory and lipid genes related to ASCVD. Microarray analyses of expression of targeted ASCVD genes from skin in 89 patients with moderate-to-severe psoriasis from the ACCEPT trial were compared with non-diseased skin from healthy controls (n = 25).

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.

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.