Identification of treatment effect modifiers and prognostic factors in newly diagnosed and relapsed or refractory multiple myeloma.

We aimed to identify variables that affect the prognosis and treatment effect in multiple myeloma (MM). Published literature of randomized controlled trials (RCTs) and population-adjusted indirect comparisons (PAICs) in newly diagnosed (ND) and relapsed/refractory (RR) MM populations reporting overall survival (OS) and progression-free survival (PFS) were identified. Possible treatment effect modifiers (TEMs) were evaluated based on the ratio between effect estimates of different strata within subgroups for OS and PFS among eligible RCTs.

Real-world frontline treatments in patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor exon 20 insertions and adjusted comparisons versus amivantamab plus chemotherapy from the PAPILLON study.

Introduction: In PAPILLON, frontline amivantamab + carboplatin + pemetrexed (ACP) demonstrated superior efficacy over carboplatin + pemetrexed in patients with advanced or metastatic non-small-cell lung cancer (aNSCLC) harboring mutations in epidermal growth factor receptor (EGFR) exon 20 insertions (exon20ins). Real-world (RW) treatment patterns and comparative effectiveness of ACP versus RW treatments are unknown.

Materials And Methods: The present study (NECTAR) retrospectively analyzed frontline treatments prescribed 2012-2023 for patients with aNSCLC and confirmed EGFR exon20ins from English (ENG-NCRD), French (FR-ESME), and US (US-COTA and US-ConcertAI) datasets.

Population-based study of disease trajectory after radical treatment for high-risk prostate cancer.

Objectives: To investigate long-term disease trajectories among men with high-risk localized or locally advanced prostate cancer (HRLPC) treated with radical radiotherapy (RT) or radical prostatectomy (RP).

Material And Methods: Men diagnosed with HRLPC in 2006-2020, who received primary RT or RP, were identified from the Prostate Cancer data Base Sweden (PCBaSe) 5.0.

A US real-world study of treatment patterns and outcomes in localized or locally advanced prostate cancer patients.

Purpose: Men with localized or locally advanced prostate cancer (LPC/LAPC) are at risk of progression after radiotherapy (RT) or radical prostatectomy (RP). Using real-world data, we evaluated patient characteristics, treatment patterns, and outcomes in LPC/LAPC.

Methods: Optum claims and electronic health records (EHR) data from January 2010 to December 2021 were queried for men with LPC/LAPC who received primary RT, RP, or androgen deprivation therapy alone within 180 days after diagnosis.

Teclistamab versus real-world physician's choice of therapy in triple-class exposed relapsed/refractory multiple myeloma.

We compared the effectiveness of teclistamab versus real-world physician's choice of therapy (RWPC) in triple-class exposed relapsed/refractory multiple myeloma. MajesTEC-1 eligibility criteria were applied to the RWPC cohort. Baseline covariate imbalances were adjusted using inverse probability of treatment weighting.

Comparative Efficacy of Teclistamab Versus Physician's Choice of Therapy in the Long-term Follow-up of APOLLO, POLLUX, CASTOR, and EQUULEUS Clinical Trials in Patients With Triple-class Exposed Relapsed or Refractory Multiple Myeloma.

Background: The efficacy and safety of teclistamab in patients with RRMM who received ≥3 prior lines of therapy and were triple-class exposed (TCE) are being evaluated in the single-arm, multicohort, phase I/II MajesTEC-1 trial (NCT04557098). We evaluated the comparative effectiveness of teclistamab versus physician's choice (PC) of therapy in TCE RRMM patients.

Methods: Individual patient-level data from MajesTEC-1 patients who received teclistamab (1.

Treatment Response With Esketamine Nasal Spray Plus an Oral Antidepressant in Patients With Treatment-Resistant Depression Without Evidence of Early Response: A Pooled Post Hoc Analysis of the TRANSFORM Studies.

To evaluate response to esketamine nasal spray plus an oral antidepressant (ESK + AD) at day 28 in patients with major depressive disorder () and treatment-resistant depression (TRD) who did not meet response criteria within the first week of treatment. The current study is a pooled post hoc analysis of two phase 3, double-blind, active-controlled studies, conducted between August 2015 and February 2018, comparing ESK + AD with an oral antidepressant plus placebo (AD + PBO). Early treatment response was defined as a ≥ 50% decrease in Montgomery-Åsberg Depression Rating Scale total score at day 2 or days 2 and 8.

Guselkumab demonstrated an independent treatment effect in reducing fatigue after adjustment for clinical response-results from two phase 3 clinical trials of 1120 patients with active psoriatic arthritis.

Background: The interleukin-23p19-subunit inhibitor guselkumab effectively treats signs and symptoms of psoriatic arthritis (PsA). We evaluated the effect of guselkumab on fatigue.

Methods: Across two phase 3 trials of guselkumab (DISCOVER-1, DISCOVER-2), patients with active PsA despite standard therapy were randomized to subcutaneous injections of guselkumab 100 mg every 4 weeks (Q4W, N = 373); guselkumab 100 mg at week 0, week 4, and then Q8W (N = 375); or placebo (N = 372) through week 24, after which patients in the placebo group crossed over to guselkumab Q4W.

Opioid Use in Patients With Inflammatory Bowel Disease.

Background: Data on opioid use in patients with inflammatory bowel disease and the relationship between disease, opioid use, and healthcare resource utilization are needed.

Methods: This analysis of real-world data from IBM Watson Health Commercial Claims and Encounters Database included patients with the first claim of inflammatory bowel disease (IBD) between 2007 and 2014.

Results: Opioid use was higher in patients with IBD than in the matched non-IBD cohort.

Reliability, validity and responsiveness of E-RS:COPD in patients with spirometric asthma-COPD overlap.

Background: The Evaluating Respiratory Symptoms in Chronic Obstructive Pulmonary Disease (E-RS:COPD) is a patient-reported diary that assesses respiratory symptoms in stable COPD.

Methods: This post hoc analysis of a randomized, double-blind, parallel-arm trial (GSK ID: 200699; NCT02164539) assessed the structure, reliability, validity and responsiveness of the E-RS, and a separate wheeze item, for use in patients with a primary diagnosis of asthma or COPD, but with spirometric characteristics of both (fixed airflow obstruction and reversibility to salbutamol; a subset of patients referred to as spirometric asthma-COPD overlap [ACO]; N = 338).

Results: Factor analysis demonstrated that E-RS included Cough and Sputum, Chest Symptoms, and Breathlessness domains, with a Total score suitable for quantifying overall respiratory symptoms (comparative fit index: 0.

Humanistic outcomes in treatment resistant depression: a secondary analysis of the STAR*D study.

Background: In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, a third of patients did not achieve remission or adequate response after two treatment trials, fulfilling requirements for treatment resistant depression (TRD). The present study is a secondary analysis of the STAR*D data conducted to compare the humanistic outcomes in patients with TRD and non-TRD MDD.

Methods: Patients with major depressive disorder who entered level 3 of the STAR*D were included in the TRD group, while patients who responded to treatment and entered follow-up from level 1 or 2 were included in the non-TRD group.

Long-Term Impact of Belimumab on Health-Related Quality of Life and Fatigue in Patients With Systemic Lupus Erythematosus: Six Years of Treatment.

Objective: To report long-term health-related quality of life (HRQoL) and fatigue outcomes in patients with systemic lupus erythematosus (SLE) receiving belimumab.

Methods: Patients with SLE who completed the Study of Belimumab in Subjects with SLE 76-week trial (BLISS-76) were enrolled in this continuation study (BEL112233 [ClinicalTrials.gov identifier: NCT00724867]).

The impact of long-term systemic glucocorticoid use in severe asthma: A UK retrospective cohort analysis.

Objective: Systemic glucocorticoids (SGCs) are a treatment option for severe asthma but are associated with the development of adverse events (AEs). Evidence on the extent of SGC use and the relationship between SGC dose and AE risk in severe asthma is limited.

Methods: Patients with severe asthma (Global Initiative for Asthma step 4/5), with no SGC use during the <6-12 months before severe asthma determination (index date) were identified in the UK-based Clinical Practice Research Datalink database (2004-2012).

The Burden of Illness Related to Chronic Obstructive Pulmonary Disease Exacerbations in Québec, Canada.

Background: Chronic obstructive pulmonary disease (COPD) prevalence in Canada has risen over time. COPD-related exacerbations contribute to the increased health care utilization (HCU) in this population. This study investigated the impact of exacerbations on COPD-related HCU.

Burden of systemic glucocorticoid-related complications in severe asthma.

Objectives: Although systemic glucocorticoids (SGCs) are efficacious, their chronic use is associated with a range of complications. Yet limited data are available about the risks following chronic use in patients with severe asthma, who are at risk of long-term SGC-related complications. This study was carried out to investigate the risks of developing SGC-related complications, and to quantify the associated healthcare resource utilization and costs for patients with severe asthma in the United States.

Dose-Response Relationship Between Long-Term Systemic Corticosteroid Use and Related Complications in Patients with Severe Asthma.

Background: Systemic corticosteroids are a leading cause of drug-related complications, yet little has been done to quantify the dose-response relationship between systemic corticosteroid exposure and complications in patients with severe asthma.

Objectives: To (a) evaluate the risk of developing systemic corticosteroid-related complications by corticosteroid exposure in severe asthma and (b) quantify the associated health care resource utilization and costs.

Methods: This is a retrospective study using administrative claims data from a large commercial database between 2003 and 2014.

Use of ICS/LABA on Asthma Exacerbation Risk in Patients Within a Medical Group.

Background: Asthma medication ratio (AMR) ≥ 0.5 has been shown to predict asthma exacerbations. This study explores the impact of increasing or decreasing inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) use over a 7-year period on achieving an AMR of ≥ 0.

Acute and chronic systemic corticosteroid-related complications in patients with severe asthma.

Background: Many patients with severe asthma require maintenance treatment with systemic corticosteroids (SCSs) to control daily symptoms and prevent serious acute exacerbations, but chronic SCS use is associated with complications.

Objective: We sought to evaluate the risk of SCS-related complications by SCS exposure and quantify the associated health care costs and resource use in patients with severe asthma.

Methods: We performed a longitudinal, open-cohort, observational study using health insurance claims data (1997-2013: Medicaid) from Florida, Iowa, Kansas, Missouri, Mississippi, and New Jersey.

A proposed modification to Hy's law and Edish criteria in oncology clinical trials using aggregated historical data.

Purpose: Identifying drug-induced liver injury is a critical task in drug development and postapproval real-world care. Severe liver injury is identified by the liver chemistry threshold of alanine aminotransferase (ALT) >3× upper limit of normal (ULN) and bilirubin >2× ULN, termed Hy's law by the Food and Drug Administration. These thresholds require discontinuation of the causative drug and are seldom exceeded in most patient populations.

Truncated robust distance for clinical laboratory safety data monitoring and assessment.

Laboratory safety data are routinely collected in clinical studies for safety monitoring and assessment. We have developed a truncated robust multivariate outlier detection method for identifying subjects with clinically relevant abnormal laboratory measurements. The proposed method can be applied to historical clinical data to establish a multivariate decision boundary that can then be used for future clinical trial laboratory safety data monitoring and assessment.

Validation of multivariate outlier detection analyses used to identify potential drug-induced liver injury in clinical trial populations.

Background: Potential severe liver injury is identified in clinical trials by ALT >3 × upper limits of normal (ULN) and total bilirubin >2 × ULN, and termed 'Hy's Law' by the US FDA. However, there is limited evidence or validation of these thresholds in clinical trial populations. Using liver chemistry data from clinical trials, decision boundaries were built empirically with truncated robust multivariate outlier detection (TRMOD), in a statistically robust manner, and then compared with these fixed thresholds.

Predicting breast cancer chemotherapeutic response using a novel tool for microarray data analysis.

We developed a novel tool for microarray data analysis that can parsimoniously discover highly predictive genes by finding the optimal trade off between fold change and t-test p value through rigorous cross validation. In addition to find a small set of highly predictive genes, the tool also has a procedure that recursively discovers and removes predictive genes from the dataset until no such genes can be found. We applied our tool to a public breast cancer dataset with the goal to discover genes that can predict patient’s response to a preoperative chemotherapy.

Genome-wide association studies using an adaptive two-stage analysis for a case-control design.

A new type of test is presented for genome-wide association studies using a case-control design. It is referred to as the adaptive two-stage (ATS) analysis, being based on both the Hardy-Weinberg disequilibrium trend test (HWDTT) and the Cochran-Armitage trend test (CATT). The procedure for the ATS is to screen single-nucleotide polymorphisms (SNPs) using the HWDTT in a first stage, and then test a reduced number of SNPs that pass the screening step in a second stage using the CATT.