Combined TNF-α and OX40L targeting as a new treatment option for hidradenitis suppurativa.

Background: Chronic inflammatory conditions are among the leading causes of disability and mortality. Although therapies have been significantly improved with the introduction of target-specific biologics, many chronic inflammatory conditions can be only moderately controlled by inhibition of individual cytokines.

Objective: We sought to compare individual versus simultaneous blockade of TNF-α and OX40L in controlling inflammation.

Patterns of calcitonin gene-related peptide monoclonal antibody use in people with migraine: Results of the OVERCOME (US) study.

BackgroundUnderstanding characteristics and reasons associated with using calcitonin gene-related peptide monoclonal antibodies (CGRP mAb) for migraine prevention may help clinicians individualize treatment plans and achieve better patient outcomes.MethodsWe analyzed 2019-2020 cohort data of OVERCOME (US), a population-based survey among adults with migraine. Eligible participants were categorized based on current CGRP mAb usage ("NEVER" and "EVER" users ["Continued", "Switched" and "Discontinued"]).

Results from an EFPIA, JPMA, PhRMA industry survey on reopening and revamping the ICH S7A guidance on safety and secondary pharmacology.

The ICH S7A guideline on safety pharmacology has remained unchanged since its inception in 2000, fulfilling its crucial role in safeguarding clinical trial participants and patients (ICH S7A). However, in the meanwhile there has been significant scientific and technological advancements in drug safety science, a paradigm shifts of the drug discovery and development process, and an continuously evolving regulatory landscape, that led to the recommendation to revisit, adapt and evolve the ICH S7A guideline (Valentin & Leishman, 2023, 2025). A revision of the guidance would imply opening an ICH process, the first step consists in the development of a 'concept paper'.

Audio review as a measure of quality assurance and control of cognitive assessments in Alzheimer's disease studies: An experience from Japanese Trial-Ready Cohort Study.

Background: Clinical trials targeting preclinical Alzheimer's disease (AD) require accurate cognitive assessments to detect subtle changes over time. Audio review of assessment sessions has been proposed as a quality assurance (QA) and control (QC) measure, yet evidence regarding its effectiveness remains limited.

Objective: We aim to investigate how audio review contributes to the QA/QC process.

CARDIORESPIRATORY FITNESS PREDICTS EEG-BASED SOMATOSENSORY RESPONSES FOLLOWING NOXIOUS MECHANICAL STIMULATION IN A CONDITIONED PAIN MODULATION MODEL.

Purpose: Existing literature indicates that physical fitness affects endogenous pain modulation capacity, potentially impacting populations with impaired pain modulation ability. However, current evidence remains inconsistent, and there is a lack of studies employing objective measures to examine this relationship. The objective of this study was to assess whether individual physical performance levels can predict endogenous pain modulation variables in the electroencephalogram (EEG).

Analytical and clinical validation of PATHWAY HER2 (4B5) assay for assessment of HER2-low/HER2-ultralow status and eligibility for trastuzumab deruxtecan in DESTINY-Breast06.

Background: The DESTINY-Breast06 study demonstrated a statistically significant and clinically meaningful improvement in progression-free survival benefit with trastuzumab deruxtecan (T-DXd) versus chemotherapy treatment of physician's choice in patients with hormone receptor-positive metastatic breast cancer (mBC) whose tumors were scored as human epidermal growth factor receptor 2 (HER2)-low [immunohistochemistry (IHC) 1+, or IHC 2+/in situ hybridization (ISH)-negative] and who had received one or more lines of endocrine therapy and no previous chemotherapy in the metastatic setting. An exploratory analysis consistently showed a benefit for patients with HER2-low and HER2-ultralow (IHC 0 with membrane staining) expression.

Materials And Methods: Analytical validation of the PATHWAY HER2 (4B5) assay (Roche HER2 4B5 assay; Roche Diagnostic Solutions) at the HER2-ultralow cut-off was carried out, including intermediate precision, inter-reader precision, and inter-laboratory reproducibility.

Multiple Switches Between Adalimumab-fkjp and Reference Adalimumab in Moderate-to-Severe Chronic Plaque Psoriasis: A Multicenter, Double-Blind, Parallel Group, Randomized Clinical Trial for Interchangeability.

Introduction: This study was conducted to fulfill the FDA requirement for the designation of adalimumab-fkjp, an FDA-approved biosimilar, as an 'interchangeable' biosimilar to the reference adalimumab. The primary objective was to evaluate the interchangeability of adalimumab-fkjp (low concentration, 40 mg/0.8 mL) with reference adalimumab (high concentration, 40 mg/0.

User Engagement with A Multimodal Conversational Agent for Self-Care and Chronic Disease Management: A Retrospective Analysis.

Introduction: Understanding user engagement with conversational agents is key to their sustainable use in mobile health and improving patient outcomes. This retrospective study analyzed interactions with a multimodal conversational agent in the Albert Health app to identify usage patterns and barriers to long-term engagement in self-care and chronic disease management.

Methods: We retrospectively analyzed interactions from 24,537 users of a Turkish-language mobile health app (between January 1, 2022, and December 31, 2023).

Stable Iodine Intake During Pregnancy and Children's Thyroid Screening Outcomes After the 2011 Fukushima Nuclear Disaster in Japan: A Municipality-based Descriptive Study.

Objectives: Stable iodine intake is an essential preventive strategy against thyroid cancer following a nuclear disaster. However, the rate of stable iodine intake during pregnancy and thyroid outcomes among their children have remaifned unclear.

Methods: This observational study used data from a thyroid screening program at Research Institute of Radiation Safety for Disaster Recovery Support in Fukushima, Japan.

J-REGISTER: real-world study of Japanese patients with mutation-positive NSCLC treated with first-line afatinib.

Aim: The J-REGISTER study assessed outcomes and subsequent treatment in patients with mutation-positive NSCLC treated with first-line afatinib, including patients with uncommon mutations.

Patients & Methods: This retrospective study assessed 805 patients treated with afatinib in Japan. The primary objective was time on treatment with afatinib.

Immunogenicity risk assessment for tailored mitigation and monitoring of biotherapeutics during development: recommendations from the European Immunogenicity Platform.

Bringing safe and effective drugs to patients is of utmost importance for the pharmaceutical industry, with immunogenicity (IG) being a critical factor that influences both aspects. Biotherapeutics can elicit unwanted immune responses, potentially leading to (severe) safety implications, reduced patient benefits, and may result in termination of development. Therefore, understanding IG risks throughout drug development is essential for both drug developers and health agencies (HAs).

Finerenone with Empagliflozin in Chronic Kidney Disease and Type 2 Diabetes.

Background: Limited evidence exists to support the simultaneous initiation of sodium-glucose cotransporter-2 inhibitors and finerenone, a nonsteroidal mineralocorticoid receptor antagonist, in persons with chronic kidney disease and type 2 diabetes.

Methods: We randomly assigned participants with chronic kidney disease (estimated glomerular filtration rate [eGFR], 30 to 90 ml per minute per 1.73 m of body-surface area), albuminuria (a urinary albumin-to-creatinine ratio of 100 to ≤5000 [with albumin measured in milligrams and creatinine measured in grams]), and type 2 diabetes, who were already taking a renin-angiotensin system inhibitor, in a 1:1:1 ratio to receive finerenone (with empagliflozin-matching placebo) at a dose of 10 or 20 mg per day, empagliflozin at a dose of 10 mg per day (with finerenone-matching placebo), or a combination of finerenone and empagliflozin.

Patient Preference on Age-Related Macular Degeneration Treatment: A Systematic Review.

Purpose: Patient preference is important in decision-making processes, such as drug approval and price determination. We conducted a systematic review regarding the preference of age-related macular degeneration (AMD) treatment.

Patients And Methods: We searched for articles on patient preferences for AMD treatment published between January 1, 2000 and December 31, 2023 using EMBASE, Google scholar, MEDLINE, and PLOS.

Population Cellular Kinetics of Idecabtagene Vicleucel in Patients with Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma.

Background: Idecabtagene vicleucel (ide-cel, ABECMA) is an autologous, B-cell maturation antigen (BCMA)-directed, chimeric antigen receptor (CAR) T-cell therapy. The current modeling analyses aim to characterize the cellular kinetics (CK) of ide-cel and to assess the covariate effects impacting ide-cel cellular kinetics in patients with relapsed/refractory multiple myeloma.

Methods: A modified piecewise model was developed to characterize ide-cel CK through the nonlinear mixed effects method.

Savolitinib plus osimertinib in epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer with MET overexpression and/or amplification following disease progression on osimertinib: primary results from the phase II SAVANNAH study.

Background: MET-based resistance following osimertinib treatment for epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC) is common. We report the primary analysis of the phase II SAVANNAH study (NCT03778229) evaluating savolitinib plus osimertinib in this setting.

Patients And Methods: Patients had EGFR-mutated, advanced NSCLC with MET overexpression and/or amplification.

Pharmacokinetics of Atogepant in Healthy Lactating Female Participants: Results from a Phase 1 Lactation Study.

Introduction: Atogepant is approved for the preventive treatment of migraine and is taken orally once daily. This work aimed to characterize the plasma and milk pharmacokinetics of atogepant in lactating females.

Methods: An open-label, phase 1 study (NCT05892757) was conducted in 12 healthy, lactating adult women 1-6 months postpartum from July 11, 2023, to February 22, 2024.

Addition of navitoclax to ruxolitinib for patients with myelofibrosis with progression or suboptimal response.

Navitoclax (oral B-cell lymphoma-2 family protein inhibitor induces apoptosis of malignant cells in myelofibrosis (MF). We present pooled cohort 1 results from the phase 2 REFINE trial, which evaluated navitoclax plus ruxolitinib (NAV+RUX) for patients with relapsed/refractory MF with suboptimal response to RUX (≥10 mg twice daily stable dose for ≥12 weeks [cohort 1a] or ≥24 weeks [cohort 1b]). Cohort 1a received add-on NAV 50 mg/d, with escalation to ≤300 mg if platelet count was ≥75 × 10/L.

RECLAIM-A retrospective, multicenter observational study aimed at enabling the development of artificial intelligence-driven prognostic models for disease progression in multiple sclerosis.

Multiple sclerosis (MS) is characterized by a progressive worsening of disability over time. As many regulatory-cleared disease-modifying treatments aiming to slow down this progression are now available, a clear need has arisen for a personalized and data-driven approach to treatment optimization in order to more efficiently slow down disease progression and eventually, progressive disability worsening. This strongly depends on the availability of biomarkers that can detect and differentiate between the different forms of disease worsening, and on predictive models to estimate the disease trajectory for each patient under certain treatment conditions.

Enfortumab vedotin plus pembrolizumab versus chemotherapy in patients with previously untreated locally advanced or metastatic urothelial cancer (EV-302): patient-reported outcomes from an open-label, randomised, controlled, phase 3 study.

Background: In the ongoing EV-302 trial, first-line enfortumab vedotin plus pembrolizumab improved progression-free survival and overall survival versus platinum-based chemotherapy in patients with locally advanced or metastatic urothelial cancer. Patient-reported outcomes (PROs) from EV-302 are reported here.

Methods: EV-302 was a phase 3, open-label, two-group, randomised global study to evaluate the combination of enfortumab vedotin plus pembrolizumab versus standard-of-care platinum-based chemotherapy (gemcitabine with cisplatin or carboplatin) in patients with previously untreated locally advanced or metastatic urothelial cancer.

Patient-reported outcomes with trastuzumab deruxtecan in hormone receptor-positive, HER2-low or HER2-ultralow metastatic breast cancer: results from the randomized DESTINY-Breast06 trial.

Background: The randomized phase III DESTINY-Breast06 trial (NCT04494425) demonstrated superior efficacy with trastuzumab deruxtecan (T-DXd) versus chemotherapy treatment of physician's choice (TPC) and no new safety signals in patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-low [immunohistochemistry (IHC) 1+, IHC 2+/in situ hybridization-negative], and HER2-ultralow (IHC 0 with membrane staining) metastatic breast cancer (mBC). Here, we report the patient-reported outcome (PRO) endpoints in the intent-to-treat (ITT; HER2-low/-ultralow) and HER2-low populations.

Patients And Methods: Patients with progressive disease (PD) after one or more prior lines of endocrine-based therapy and no prior chemotherapy for mBC were assigned 1 : 1 to T-DXd 5.

Stable iodine intake and thyroid screening outcomes after the Fukushima Nuclear Disaster: an observational study.

Context: Stable iodine intake is crucial in preventing thyroid cancer after radiological emergencies; however, the association between stable iodine intake and thyroid outcomes in children after the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident remains unclear.

Objective: To describe thyroid screening outcomes and investigate the association between stable iodine intake and those outcomes in children after the FDNPP accident.

Design: Observational study.

An exploratory trial of a single dose of CAM2043 (treprostinil subcutaneous depot) in systemic sclerosis-related Raynaud's phenomenon.

Objectives: Our aim was to explore the effect of a single subcutaneous dose of CAM2043, a novel extended-release subcutaneous formulation of treprostinil, on finger temperature in patients with systemic sclerosis (SSc)-related Raynaud's phenomenon (RP).

Methods: This was an exploratory, open-label, single-dose Phase 2 trial. Ten female patients (median age 54.

Effects of Pemafibrate on Cholesterol Synthesis and Absorption: a Post-Hoc Subgroup Analysis of a Phase 2 Clinical Trial.

Aim: Recently, we reported that a pemafibrate extended-release (XR) formulation lowered low-density lipoprotein cholesterol (LDL-C) and cholesterol synthesis and absorption markers in a phase 2 clinical pharmacology study. Here we describe our post-hoc analysis of that study, discuss the mechanism by which pemafibrate lowers LDL-C, and suggest which patients may respond favorably to pemafibrate treatment.

Methods: In the phase 2 study, patients with hypertriglyceridemia received treatment with pemafibrate immediate-release (IR) 0.