Advances in Therapy最新文献

Introduction

Fremanezumab, a monoclonal antibody (mAb) targeting the calcitonin gene-related peptide (CGRP) pathway, and gepants, small molecule CGRP receptor antagonists, are both approved for the treatment of migraine or its symptoms. This study assessed effectiveness, tolerability, and migraine-related healthcare resource utilization (HCRU) after the addition of fremanezumab for preventive migraine treatment in patients using gepants for acute treatment.

Methods

Data were extracted during a retrospective chart review from electronic medical records from the Dent Neurologic Institute. Eligible patients were ≥ 18 years old, using gepants (rimegepant or ubrogepant), who initiated fremanezumab between January 1, 2020, and May 1, 2021 (index date: date of fremanezumab initiation) and continued concomitant use of gepants and fremanezumab for ≥ 1 month (post-index; between 7–9 months of follow-up). Outcomes included monthly migraine days (MMD), adverse events (AEs), reasons for discontinuation, and migraine-related HCRU.

Results

A total of 55 patients [female, 93%; mean (SD) age, 43.5 (13.5) years] met the inclusion criteria. All patients were diagnosed with chronic migraine. Patients had an average (SD) MMD of 15.8 (7.4) at the index date. Average (SE) change in MMD from index date to post-index was − 6.5 (1.0) days (p < 0.0001). Five patients (9.1%) experienced AEs post-index; no serious AEs (SAEs) were reported. The number of migraine-related medications used decreased from the index date to post-index by a mean of 0.6 for preventive medications (p = 0.070), and 0.8 for acute medications (p = 0.050). The number of outpatient office-based visits also decreased [mean (SD): 6 months pre-index, 5.8 (4.4) vs. 6 months post-index, 4.1 (4.0); p < 0.0001].

Conclusion

The addition of fremanezumab preventively to gepants for acute migraine treatment was effective, resulted in fewer outpatient office visits, and yielded no SAEs or AEs that were novel to these migraine medication classes.

Introduction

The burden of severe asthma on patients, especially on those with concomitant chronic rhinosinusitis with nasal polyps (CRSwNP), is substantial. Treatment intensification with oral corticosteroids is a common strategy for managing severe asthma exacerbations; however, prolonged exposure to systemic corticosteroids is associated with multisystem toxicity. This study aimed to quantify the association between oral corticosteroid use and annual asthma-related costs in patients with severe asthma with or without CRSwNP.

Methods

This pharmacoeconomic analysis was based on data from the Severe Asthma Network in Italy (SANI) registry. Asthma-related costs were estimated in the context of the Italian healthcare system and included exacerbations requiring treatment intensification, unplanned visits, admissions to hospital and emergency/intensive care units, and lost workdays. For each item, the mean annual cost per patient was estimated based on national tariffs and the frequency of the event. To quantify the association between oral corticosteroid treatment and costs, the study cohort was stratified according to oral corticosteroid use in the 1-year preceding inclusion in the SANI registry.

Results

A total of 669 patients from the SANI registry were included in the present analysis, 255 of whom had concomitant CRSwNP. Corticosteroid use was associated with significantly higher annual disease-related costs per patient compared with no corticosteroid use. Compared with the overall study cohort and patients without CRSwNP, patients with CRSwNP had higher disease-related costs (higher by €1307 and €1869, respectively).

Conclusion

Use of corticosteroids, in particular systemic corticosteroids, is associated with an increase in asthma-related costs. The concomitant presence of CRSwNP impacts negatively on costs. This study suggests that a thorough analysis of costs, expected benefits, and occurrence of adverse events is required when selecting treatment intensification strategies for managing uncontrolled severe asthma.

Introduction

Chronic kidney disease-associated pruritus (CKD-aP) is a common, yet underdiagnosed condition among patients on hemodialysis. Considering the lack of established treatment pathways, we sought to evaluate the use of antidepressant, systemic antihistamines, or gabapentinoid medications among patients with CKD-aP in the year following pruritus assessment.

Methods

We included 6209 patients on hemodialysis in the analysis. We retrospectively extracted clinical and patient-reported data from electronic health records. The intensity of CKD-aP was assessed by KDQOL-36 and 5-D Itch questionnaires. Prescription of antidepressant, antihistamine, and gabapentinoids was ascertained by the occurrence of a relevant active medical order in patients’ medical records.

Results

We observed a consistent and graded association between the severity of CKD-aP and the use of antidepressant, systemic antihistamines, and gabapentinoid medications. This association remained consistent and intensified over the duration of the year after pruritus screening. This trend was robust even after accounting for potential confounding factors.

Conclusions

Patterns of antipruritic medication use in a cohort of patients with CKD-aP was identified and the frequent use of off-label treatments in the absence of approved therapies was highlighted. These observations reflect clinical practices aimed at managing severe pruritus but do not imply a causal relationship between the medications and pruritus severity. Even though we cannot exclude the possibility that these drugs have been prescribed to treat medical conditions warranting their use, previous evidence suggested that doctors may also use such medications in an attempt to buffer CKD-aP. These findings underline the importance of further elucidating current treatment strategies adopted in clinical practice to address CKD-aP.

Introduction

Metabolic dysfunction-associated steatohepatitis (MASH), the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), is linked to cardiometabolic risk factors such as obesity and type 2 diabetes (T2D). The rising prevalence of MASH and risk of hepatic and extra-hepatic complications emphasize the need for a better understanding of disease progression and associated outcomes. This study aimed to evaluate the incidence of, and demographic and clinical characteristics associated with, progression to MASH-related complications by disease severity in patients with non-cirrhotic MASH or MASH cirrhosis. Alignment between noninvasive tests (NITs) and biopsy-determined fibrosis stage was also assessed.

Methods

This analysis used data from the TARGET-NASH cohort that includes adults with MASH across academic and community sites in the United States. Patients with non-cirrhotic MASH or MASH cirrhosis were stratified by disease severity based on fibrosis stage or cirrhosis. Progression to MASH-related outcomes, including all-cause mortality, cirrhosis, and liver transplantation, was assessed.

Results

Among the 2378 patients included in this analysis, 48% had MASH cirrhosis. Incidence of all-cause mortality increased with disease severity from 0.14/100 person-months (100PM) at fibrosis stage 0–1 (F0–F1) to 2.02/100PM with compensated cirrhosis and 4.62/100PM with decompensated cirrhosis. Compared with patients with F0–F1, risk of progression to cirrhosis was higher in patients with F3 [hazard ratio (HR), 95% confidence interval (CI); 18.66, 10.97–31.73] and F2 (HR, 95% CI; 3.74, 2.00–6.98). Among those who progressed to MASH-related outcomes, 67.9% had T2D and 73.9% had hypertension. Vibration-controlled transient elastography showed better alignment with biopsy-determined fibrosis stage than Fibrosis-4 Index (FIB-4).

Conclusions

Progression to all-cause mortality in patients with MASH was significantly associated with the presence of higher fibrosis stage and cirrhosis. Cardiometabolic comorbidities such as T2D and hypertension were prevalent in patients with MASH progression. Early identification and management of MASH may mitigate disease progression and liver-related complications.

Introduction

This study evaluated the safety and tolerability of fezolinetant in women with vasomotor symptoms (VMS) due to menopause in a pooled analysis of data from three 52-week phase 3 studies (SKYLIGHT 1, 2, and 4).

Methods

SKYLIGHT 1 and 2 were double-blind, placebo-controlled studies where women (≥ 40 to ≤ 65 years), with moderate to severe VMS (minimum average ≥ 7 hot flashes/day) were randomized to once-daily placebo, fezolinetant 30 mg or 45 mg. After 12 weeks, those on placebo were re-randomized to fezolinetant 30 mg or 45 mg, while those on fezolinetant continued on their assigned dose for 40 weeks. SKYLIGHT 4 was a placebo-controlled, double-blind, 52-week safety study. Safety was assessed by frequency of treatment-emergent adverse events (TEAEs) and endometrial events. TEAEs of special interest included liver test elevations and endometrial hyperplasia or cancer or disordered proliferative endometrium.

Results

Totals of 952 participants receiving placebo, 1100 receiving fezolinetant 45 mg, and 1103 receiving fezolinetant 30 mg took ≥ 1 dose of study medication. TEAEs occurred in 55.3%, 62.9%, and 65.4%, respectively; exposure-adjusted results were consistent with these results. Most frequent TEAEs in fezolinetant-treated participants included upper respiratory tract infection (7.7–8.3%), headache (6.8–8.2%), coronavirus disease 2019 (5.8–6.1%), back pain (3.1–3.7%), arthralgia (2.9–3.2%), diarrhea (2.3–3.2%), urinary tract infection (2.9–3.4%), and insomnia (2.0–3.0%). The incidence of drug-related serious TEAEs and associated treatment withdrawals was low. Elevations in liver transaminases occurred in 1.5–2.3% of fezolinetant-treated participants, were typically asymptomatic and transient, resolved on treatment or discontinuation, with no evidence of severe drug-induced liver injury (Hy’s law). Endometrial safety results were well within US Food and Drug Administration criteria. Analysis of benign and non-benign neoplasm controlled for exposure demonstrated no increased risk versus placebo.

Conclusion

Pooled data confirm the safety and tolerability of fezolinetant over 52 weeks.

Trial Registration

ClinicalTrials.gov identifiers, NCT04003155, NCT04003142, and NCT04003389.

Graphical abstract available for this article.

Graphical Abstract

Introduction

Chronic obstructive pulmonary disease (COPD) is associated with exacerbations which can reduce quality of life and increase mortality. Single-inhaler triple therapy (SITT) is recommended for maintenance treatment of COPD among patients experiencing exacerbations despite dual-therapy use. This real-world comparative effectiveness study compared the impact of SITTs, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI), and budesonide/glycopyrrolate/formoterol fumarate (BUD/GLY/FORM), on COPD exacerbations and mortality.

Methods

Medicare Fee-for-Service (FFS) patients with COPD initiated on FF/UMEC/VI or BUD/GLY/FORM were identified from the Komodo Research healthcare claims dataset (01/01/2016–12/31/2023). Overlap weighting based on high-dimensional propensity scores evaluated from patient characteristics was used to adjust for baseline confounding. Primary outcome was annualized rate of moderate–severe COPD exacerbations (per patient-year; PPY) compared using rate ratios (RRs) with 95% confidence intervals (CIs) from weighted Poisson regression models. Secondary and exploratory outcomes were risk of moderate–severe COPD exacerbations and all-cause mortality, respectively, evaluated using Kaplan–Meier analysis and hazard ratios (HR) with 95% CIs from Cox proportional hazard models. A secondary analysis was conducted among a mutually exclusive population with Medicare Advantage, Medicaid, or commercial insurance.

Results

Overall, 32,312 FF/UMEC/VI and 12,230 BUD/GLY/FORM Medicare FFS patients were included. After weighting, median follow-up was 9 months. Compared with BUD/GLY/FORM, FF/UMEC/VI users had a 12% lower rate of annualized moderate–severe COPD exacerbations [0.80 and 0.91 PPY; RR (95% CI): 0.88 (0.85–0.92); P < 0.001] and a 10% lower risk of moderate–severe exacerbations at 12 months post-initiation [HR (95% CI): 0.90 (0.87–0.93); P < 0.001], driven by moderate exacerbations. FF/UMEC/VI compared with BUD/GLY/FORM users had 11% lower risk of all-cause mortality at 12 months post-initiation [5.6% vs. 6.4%; HR (95% CI): 0.89 (0.80–0.98); P = 0.020]. Results were consistent among patients with Medicare Advantage, Medicaid, or commercial insurance.

Conclusions

In this real-world comparative effectiveness study, FF/UMEC/VI was associated with significantly lower rate and risk of COPD exacerbations than BUD/GLY/FORM.

Introduction

The aim of the observational SIMPLE study was to assess real-life effectiveness and safety of a single-pill combination (SPC) of perindopril arginine/amlodipine in a broad range of subjects with newly diagnosed mild-to-moderate hypertension treated in Canadian general practice.

Methods

Treatment-naïve participants aged 18–65 years with mild-to-moderate hypertension, whose physicians decided to initiate the perindopril/amlodipine SPC, were recruited from Canadian clinical practice from October 2017 to February 2019. Participants were followed at 3- (M3) and 6-month (M6) visits after treatment initiation. The recommended starting dose of 3.5 mg/2.5 mg once daily was up-titrated, at the discretion of the treating physician, if blood pressure (BP) remained above target at subsequent visits. The primary endpoint was change in mean office systolic BP (SBP) and diastolic BP (DBP) at M6.

Results

The full analysis set included 1179 participants with a mean age of 51.5 ± 8.7 years; 61% were male. Mean SBP/DBP at baseline was 153.4 ± 11.5/94.8 ± 7.7 mmHg. Treatment was initiated at 3.5 mg/2.5 mg in 76.0% participants. Over the 6-month treatment period, significant (P < 0.001) decreases from baseline were observed for SBP (− 22.9 ± 14.5 mmHg) and DBP (− 13.4 ± 9.1 mmHg), with 70.2% of participants achieving their BP target. Across all perindopril/amlodipine SPC dose groups, 61.4% of participants achieved BP targets at M3; mean SBP was reduced by 20.8 ± 14.7 mmHg and DBP by 11.7 ± 9.2 mmHg (both P < 0.001). Analysis by baseline subgroup revealed significant BP reductions across age groups, sex, hypertension grades, and diabetes status. Participants with Grade 2 hypertension had a significantly greater decrease than those with Grade 1 (P < 0.001). Treatment with the SPC was well tolerated, and in the 6.1% with treatment-related adverse events, the majority were mild to moderate. High (99%) self-reported adherence (< 20 missed doses) in the 49.4% with available data and high physician satisfaction with treatment (82%) were reported.

Conclusion

Data from routine Canadian clinical practice indicate that a perindopril/amlodipine SPC is associated with significant BP reductions from baseline in a broad range of participants with different cardiovascular risk factors and may represent an appropriate first-line treatment for subjects with newly diagnosed hypertension.

Introduction

The present study aimed to investigate the prescribing patterns of anticholinergics (anti-AChR) or β3-adrenergic agonists (β₃A) in the pharmacotherapy of overactive bladder (OAB) and to evaluate the differences in the frequency of adverse events (AEs) between the two types of drugs using a large-scale medical claims database.

Methods

This cohort study was conducted using the JMDC claims database between May 2015 and April 2023. Patient characteristics, prescription and treatment patterns of anti-AChR and β₃A, and the incidence of AEs have been described.

Results

Overall, 70,936 patients were analyzed [mean age, 53.6 (standard deviation: 12.3) years]. Among women (48.5%; 34,439), 21.4% initially received anti-AChR and 27.2% received β₃A; among men (51.5%; 36,497), 17.1% initially received anti-AChR and 34.3% received β₃A. Most patients (79.6%; women, 83.5%; men, 75.8%) visited clinics. About 10% of patients had a treatment change: 5.6% switched the drug type (change from anti-AChR to β₃A or vice versa), and 4.0% had an add-on of another drug type. The incidence rate of treatment change per 100 patient-years was higher with β₃A in both women (12.39) and men (13.65). In the multivariable analysis, initial prescription with anti-AChR compared with β₃A did not show any association with the risk of AEs.

Conclusion

This large-scale database study revealed that treatment for OAB is often initiated with β₃A and prescribed mainly at clinics. Changes or additions to initial prescriptions were as low as about 5%, indicating that raising awareness among physicians treating OAB is particularly important to improve the quality of life of patients with OAB. Our study also showed that the incidence of AEs was not associated with the initially prescribed drug type. Continued exploration is warranted to further clarify the risk of AEs with each prescription.

Introduction

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial pneumonia, which is characterised by progressive worsening of dyspnoea and lung function. Nintedanib treatment is recommended to slow IPF disease progression. The aim of this post-marketing surveillance (PMS) study was to evaluate the safety and effectiveness of nintedanib over 24 months in patients with IPF in a real-world setting in Japan.

Methods

This prospective, non-interventional, all-case PMS study of nintedanib included Japanese patients with IPF who started nintedanib between 7 October 2015 and 2 May 2023. The primary outcome was to determine the proportion of patients with adverse drug reactions (ADRs), and the secondary outcome was the adjusted absolute change from baseline in forced vital capacity (FVC) at 24 months.

Results

In total, 5717 patients from 1013 institutions were included in the safety analysis (mean ± standard deviation age 71.7 ± 8.1 years, 78.1% male, 70.8% current or former smokers). Most patients (83.9%) had initiated nintedanib at a dose of 150 mg capsules twice daily. At 24 months, 2841 patients (64.8%) had discontinued nintedanib, mainly due to adverse events (44.0%), ADRs (24.1%) or insufficient effectiveness (5.7%). The most common ADRs were diarrhoea (35.5%), hepatic function abnormal (14.4%), decreased appetite (9.9%), liver disorders (7.8%) and nausea (5.8%). The adjusted absolute mean change in FVC from baseline to 24 months was − 212.3 mL (95% confidence interval − 235.3, − 189.3).

Conclusion

This is the largest prospective study to investigate patients with IPF who were treated with nintedanib. The safety and effectiveness of nintedanib treatment in this real-world setting of Japanese patients with IPF was similar to that reported in previous studies. Nintedanib effectively slowed the progression of IPF. No new safety concerns were identified, and the need for appropriate management of hepatic disorders and diarrhoea (as per the approved product information) was confirmed.

Study Registration

ClinicalTrials.gov (NCT02607722)/European Union electronic register of Post-Authorisation Studies (EUPAS10891).