Advances in Therapy最新文献

Introduction

Patients with atopic dermatitis (AD) often have other comorbid type 2 inflammatory conditions. The aim of this study was to evaluate the impact of type 2 comorbidities on the response to and safety of dupilumab in young children with AD.

Methods

LIBERTY AD PRESCHOOL part B was a randomized, placebo-controlled trial in children aged 6 months to 5 years with moderate-to-severe AD. In this post hoc analysis, patients were stratified by the presence or absence of caregiver-reported selected type 2 comorbidities at baseline: asthma, allergic rhinitis (AR), and food allergies (FAs).

Results

At week 16, significantly more patients receiving dupilumab versus placebo, with or without asthma and AR, achieved an Investigator’s Global Assessment (IGA) score of 0/1 and a ≥ 75% improvement in Eczema Area and Severity Index (all p < 0.05). Significantly more patients receiving dupilumab versus placebo with FAs and numerically more patients without FAs achieved an IGA score of 0/1 (p = 0.0007 and p = 0.06). Numerically more patients receiving dupilumab versus placebo with asthma and significantly more patients without asthma achieved a ≥ 4-point reduction in the weekly average of daily score on the Worst Scratch/Itch Numeric Rating Scale (WSI-NRS) (p = 0.6 and p < 0.0001). Additionally, significantly more patients receiving dupilumab versus placebo with or without AR (p = 0.008 and p < 0.0001) and with or without FAs (p = 0.0002 and p = 0.004) achieved a ≥ 4-point reduction in the weekly average of daily score on the WSI-NRS. Overall safety was consistent with the known dupilumab safety profile.

Conclusions

Dupilumab treatment improves AD signs and symptoms in children aged 6 months to 5 years with and without type 2 comorbidities such as asthma, AR, and FAs.

Trial Registration

ClinicalTrials.gov registration number NCT03346434.

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Introduction

Nintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF), other forms of progressive pulmonary fibrosis (PPF), and systemic sclerosis-associated interstitial lung disease (ILD). We present global post-marketing safety data for nintedanib in these fibrosing ILDs.

Methods

Data on adverse events in patients with fibrosing ILDs who were treated with nintedanib were collected via spontaneous reporting and solicited reporting in various studies (excluding clinical trials). Data were collected from 15 October 2014 (first regulatory approval) to 15 October 2023. Adverse events were coded using the Medical Dictionary for Regulatory Activities. Cumulative exposure to nintedanib was estimated using sales data.

Results

Cumulative exposure to nintedanib was 380,557 patient–years. Diarrhoea was reported at a rate of 227.5 per 1000 patient–years. Only 2.6% of diarrhoea events were reported as serious. Of 39,788 (33.6%) diarrhoea events with a known time to onset, almost 60% occurred within the first 3 months of treatment. The rate of serious liver enzyme and bilirubin elevations (including drug-induced liver injury) was 4.0 per 1000 patient–years. Bleeding was reported at a rate of 24.2 per 1000 patient–years. Most (81.3%) bleeding events were non-serious. The rates of myocardial infarction, ischaemic stroke, and venous thromboembolism were 3.3, 3.3, and 2.0 per 1000 patient–years, respectively. Gastrointestinal perforation was reported at a rate of 0.9 per 1000 patient–years.

Conclusion

Post-marketing safety data on established and potential adverse events associated with nintedanib in patients with fibrosing ILDs, collected over 9 years, demonstrated a safety profile that was similar to that established in clinical trials and provided in the product labels. Education of patients about the adverse events that may be associated with nintedanib, and the effective management of adverse events when they occur, is important to minimise the impact of adverse events and help patients remain on treatment.

Introduction

Immune checkpoint inhibitors (ICIs) greatly improved outcomes of stage IV non-small cell lung cancer (NSCLC) in randomized clinical trials. Limited data exists regarding the survival improvement of ICI use at the population level.

Methods

Clinical data of patients with pathologically confirmed stage IV NSCLC diagnosed in 2013 and 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Survival outcomes were compared before and after ICI use to assess the survival improvement in the immunotherapy era in the real world.

Results

A total of 19,433 patients with stage IV NSCLC were included. Being female, age < 60 years, of American Indian and Asian or Pacific Islander race, married, non-squamous histology, without bone, brain, or liver metastases, and receiving chemotherapy were significantly associated with better prognosis in multivariable analyses. Propensity score matching (PSM) based on associated factors resulted in 8743 patients each in the non-immunotherapy and immunotherapy groups (1:1 ratio). After PSM, both overall survival (OS) (p < 0.001) and cancer-specific survival (CSS) (p < 0.001) were significantly improved in the immunotherapy group. The median OS (mOS) was 6.0 months in the non-immunotherapy group and 8.0 months in the immunotherapy group. The 1-, 2-, and 3-year OS rate was 29.0%, 14.2%, and 8.5% in the non-immunotherapy group, and 37.8%, 23.5%, and 16.7% in the immunotherapy group, respectively. Patients who were male, under 60 years old, married, white, had adenocarcinoma, had no bone or liver metastases, and received chemotherapy or radiation therapy were more likely to benefit from immunotherapy.

Conclusions

Survival outcomes of patients with stage IV NSCLC were significantly improved in the immunotherapy era. Population-level benefits of survival varied among subgroups, and not all the increase in OS meant a clinically meaningful benefit.

Introduction

Previous real-world evidence suggests that prompt versus delayed initiation of single-inhaler triple therapy (SITT) with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) following an exacerbation results in improved clinical outcomes for patients with chronic obstructive pulmonary disease (COPD). This prior study was conducted in the first 2 years following FF/UMEC/VI approval, representing early trends. The current updated analysis aims to further elucidate the real-world evidence for FF/UMEC/VI.

Methods

This was a retrospective cohort study using the IQVIA PharMetrics^® Plus database. Patients with COPD initiating SITT with FF/UMEC/VI within 6 months of an exacerbation (index date) were classified as prompt (≤ 30 days following exacerbation) or delayed (31–180 days) initiators. The baseline period comprised the 12 months prior to index. Inverse probability of treatment weighting was used to balance differences in baseline characteristics between cohorts. COPD exacerbations, hospital readmission rates, and healthcare costs were compared between cohorts post-index.

Results

Overall, 5421 patients (prompt, 2057; delayed, 3364) were included. After weighting, baseline characteristics were well balanced between cohorts. For up to 12 months post-index, prompt initiators of FF/UMEC/VI had significantly lower rates of exacerbations per person-year versus delayed initiators (0.74 vs. 1.06; rate ratio 0.70, 95% confidence interval [CI] 0.64–0.77; P < 0.001). A 1-day delay in FF/UMEC/VI initiation was associated with a 0.31% increase in the rate of exacerbations. At 90 days post-index, Kaplan–Meier rates of all-cause (hazard ratio [HR] 0.62, 95% CI 0.45–0.86; P = 0.004) and COPD-related (HR 0.58, 95% CI 0.35–0.98; P = 0.042) hospital readmissions were significantly lower in the prompt versus delayed cohort. Total COPD-related healthcare costs per person per year were significantly lower for patients in the prompt versus delayed cohort.

Conclusion

Healthcare providers should consider the positive impact of prompt FF/UMEC/VI initiation on exacerbation rate, hospital readmission rate, and costs when treating patients with COPD at risk of exacerbations.

Introduction

Sex and gender are crucial variables in understanding brain development and disease. Biological sex is determined by genetic and hormonal factors, whereas gender is a multidimensional construct shaped by social and cultural influences. The interplay of these factors contributes to sex-specific susceptibilities and disease progression in psychiatric and neurological disorders. However, sex and gender are often considered as a single variable, which can lead to biased data analysis and interpretation.

This commentary aims to analyze how sex and gender influence brain structure and function, with implications for personalized medicine, research, and the development of gender-sensitive clinical guidelines.

Methods

Findings from various studies employing neuroimaging techniques and animal models are discussed, as well as the impact of biological sex, gender, environmental, cultural, and social factors on brain development, organization, and behavior.

Results

Evidence suggests that sex differences in brain structure and function are not only genetically determined but are also influenced by gender-related experiences and societal contexts. Importantly, discrepancies between male and female brains are reduced in gender-equal societies. Preclinical studies play a pivotal role in determining the influence of biological sex, independent of gender, in different disease models.

Conclusion

The findings underscore the need to consider both sex and gender in research and clinical practice to avoid biases and promote equitable health outcomes. Moving forward, we advocate for gender-sensitive approaches to be integrated into brain research and in clinical guidelines to achieve personalized and precision medicine.

Bullous pemphigoid (BP) is an autoimmune blistering disease that most often affects elderly individuals and has a significant negative impact on quality of life. The disease is characterized primarily by autoantibodies to hemidesmosomal proteins BP180 and/or BP230, and an inflammatory reaction with notable features of type 2 inflammation, including elevated serum IgE, increased numbers of eosinophils in lesions and peripheral blood, and elevated expression of type 2 cytokines and chemokines in skin lesions. In this review, we present what is known about BP pathophysiology, including the role of type 2 inflammation, and discuss how findings from studies of biologics targeting type 2 immune mediators have helped to clarify the biological mechanisms driving BP pathophysiology. Future studies of these targeted therapies and others in development will help to further elucidate the mechanisms underlying BP pathophysiology and potentially provide better treatment options for patients.

Endometriosis is a common disease, affecting approximately 5–10% of reproductively aged women. Symptoms, such as painful periods, negatively impact an individual’s quality of life; however, these symptoms are often normalized, leading to delays in diagnosis and treatment, and worsening of the disease. In this podcast, a reproductive endocrinologist (Dr Sanjay K Agarwal) and patient advocate (Tara Mangum) provide their perspectives on the diagnosis and management of endometriosis. They also discuss Relugolix combination therapy as a treatment option for patients with endometriosis.

Podcast available for this article.

Background

While patients with cancer have traditionally received oncology treatments through intravenous (IV) administration, some therapies are becoming available via alternative modes of administration, such as subcutaneous (SC). This study aimed to evaluate IV versus SC therapy administration from the perspectives of the patient, healthcare provider (HCP), and healthcare system.

Methods

A systematic review was conducted, searching MEDLINE and Embase databases from 2000 to 2022. This was supplemented with grey literature searches of additional sources such as conference proceedings. Observational studies and clinical trials were included if they assessed adult patients with any cancer type who were treated with pharmacologic therapies administered via IV or SC and included patient- or HCP-reported outcomes or healthcare system perspectives on the mode of administration. Records identified by the literature search were screened by two independent reviewers. Included studies were data extracted by a single reviewer and validated by a second reviewer and synthesized using a narrative approach.

Results

After screening, 33 unique studies were included in the systematic review. Patients and HCPs reported substantially more favorable preference rates for SC over IV treatment. Additionally, from the patient perspective there were reductions in treatment time and economic burden for SC compared with IV therapy. From the HCP’s perspective, treatment time was consistently reduced by SC compared with IV treatment administration. Although information on the impact of SC and IV treatments for oncology on healthcare systems was limited, the use of SC formulations showed consistent cost savings (direct costs) and time savings from this perspective considering various uptake scenarios compared with IV administration.

Conclusion

Compared with IV administration, SC oncology treatment is a preferred option by patients and HCPs, increasing optionality and reducing treatment time while simultaneously increasing capacity and reducing the financial burden on healthcare systems.

Introduction

In Japan, patients with chronic obstructive pulmonary disease (COPD) can be escalated to treatment with inhaled triple therapy. Two single-inhaler triple therapies combining an inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β₂-agonist (ICS/LAMA/LABA) are approved maintenance therapies for patients with COPD, and multiple-inhaler triple therapies (MITTs) are also available. There is limited evidence regarding real-life treatment patterns and characteristics of patients with COPD initiating triple therapies.

Methods

This observational, retrospective cohort study identified patients with COPD in Japan from an administrative claims database (May 2018–December 2021). Demographics, clinical characteristics, and healthcare resource utilization (HCRU) were assessed in four cohorts initiating a triple therapy: budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) early adopters (initiated ≤ 12 months after market approval [September 1, 2019]), contemporary BGF users (initiated > 12 months after market approval), fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) users, and any MITT users.

Results

A total of 636 patients were BGF early adopters, 2558 were contemporary BGF users, 11,187 used FF/UMEC/VI, and 5931 used MITT. The percentage of patients with concomitant asthma in each cohort was 73.0%, BGF early adopter; 74.2%, contemporary BGF; 75.7%, FF/UMEC/VI; and 84.5%, MITT. During the 12-month baseline period, the frequency of patients with ≥ 1 moderate/severe exacerbation was 18.2%, BGF early adopter; 14.3%, contemporary BGF; 13.1%, FF/UMEC/VI; and 14.0%, MITT. ICS/LABA treatment during baseline was the most frequent pathway to triple therapy, ranging from 38.2% to 51.7% across cohorts. HCRU was relatively high across cohorts (range of hospital outpatient visits/patient during the 12-month baseline period, 11.0–14.1). Multimorbidity was observed in > 80% of patients in all cohorts; cardiovascular diseases were among the most common.

Conclusion

Many patients initiating triple therapy for COPD had concomitant asthma and had previously received ICS/LABA maintenance therapy. Patients prescribed BGF in the initial post-launch period were more likely to have a previous exacerbation history versus other cohorts, indicating more severe disease.