Drugs - Real World Outcomes最新文献

Background: Vulvovaginal candidiasis (VVC) is a common gynecological complaint. Ibrexafungerp (brand name: Brexafemme®) is a new, first-in-class oral antifungal medication approved as a 1-day treatment for VVC and as a monthly treatment to reduce frequency of recurrent VVC.

Objective: This article describes characteristics of patients who received ibrexafungerp and potential ibrexafungerp-related side effects in order to help inform optimal future use of this medication.

Methods: We used a large, national commercial health insurance claims database (the Merative^TM MarketScan® Commercial/Medicare Database) to identify female patients with one or more outpatient ibrexafungerp prescription during 1 July 2021 to 31 December 2023. We examined patient demographic characteristics, medical conditions and medications, type of healthcare provider seen, diagnostic testing performed, and potential ibrexafungerp side effects.

Results: Among 1368 female patients who received ibrexafungerp, most were also prescribed fluconazole or topical antifungals (84.7%) or had one or more vaginitis/vulvitis-related healthcare visit (76.9%) in the previous year. Few patients (2.9%) experienced a potential ibrexafungerp-related side effect.

Conclusions: Our results suggest that ibrexafungerp was generally used as non-first-line treatment for VVC.

Background and objectives: Oropharyngeal dysphagia (OD), a dysfunction in swallowing food or drink, can result from various diseases and adverse drug reactions. OD is a risk factor for aspiration pneumonia (AP). However, the specific drugs causing OD and their incidence rates are not fully understood. This study aimed to identify drugs associated with OD, their incidence rates, and AP risk factors in patients taking these drugs on the basis of the information provided in package inserts.

Methods: This study identified candidate dysphagia-inducing drugs (CDIDs) from Japanese package inserts that listed OD as an adverse reaction. The age, sex, medications, and comorbidities of patients taking CDIDs were analyzed using the JammNet insurance database, purchased from JammNet Co., Ltd. (Tokyo, Japan).

Results: Overall, 54 ingredients were identified as CDIDs. Out of 24,276 patients taking CDIDs, 146 (0.6%) were diagnosed with OD and 76 (0.3%) with AP. Among those with AP, 23 patients (30%) also had OD. OD or AP occurred in patients taking 28 (52%) of the 54 target ingredients. In addition, 13 ingredients had an adverse reaction incidence of 1% or greater for either condition. The top five CDIDs with the highest incidence rates for each diagnosis were clobazam, baclofen, zonisamide, tiapride hydrochloride, and topiramate. Incidence rates of OD and AP were significantly higher with multiple CDIDs than with a single drug (p < 0.05). Logistic regression analysis showed that AP occurrence was significantly associated with males, late-stage elderly individuals, a diagnosis of OD, and constipation.

Conclusions: The results of this study suggest that careful attention should be given to the risk of AP when prescribing CDIDs, particularly for elderly male patients.

Introduction: Pulmonary arterial hypertension (PAH) is a rare, chronic and progressive disease with a significant clinical, social, and economic impact. Despite available therapies, none address the underlying cause but rather focus on symptom management.

Objectives: This study aims to estimate the economic and social burden of PAH in Italy, including direct healthcare costs, direct nonhealthcare costs, and indirect costs related to productivity loss.

Methods: A bottom-up prevalence-based cost-of-illness model was developed using epidemiological data and healthcare resource consumption from national and international literature, validated by a panel of expert clinicians with extensive experience in the management of the condition across different regions of Italy. The analysis was conducted from a societal perspective over a 1-year horizon. The economic burden included direct healthcare costs (hospitalization, pharmaceuticals, and specialist care), direct nonhealthcare costs, and indirect costs related to productivity loss.

Results: In Italy, the prevalent population of patients with PAH is estimated between 2100 and 3500 individuals, with 2-5% in functional class (FC) I, 28-31% in FC II, 53-57% in FC III, and 7-11% in FC IV. The total annual expenditure for treatment and management is estimated between 263 million and 438 million euros, with 74% attributable to direct healthcare costs, 9% to direct nonhealthcare costs, and 17% to indirect costs. The mean annual cost per patient is approximately 125,000 € and increases with disease severity, ranging from 46,303 € for FC I to 252,176 € for FC IV.

Conclusions: PAH has a substantial economic burden, increasing with disease severity. Early diagnosis and targeted interventions could improve patient outcomes, reduce complications, and optimize resource allocation for the National Health Service and society.

Background: Chronic obstructive pulmonary disease (COPD) is a significant public health concern, and inhalation therapy is a critical component of its management. However, using an inhaler is challenging, especially for patients with COPD, who are often elderly and experience reduced dexterity, visual and cognitive impairment, and difficulty synchronizing inhalation with dose actuation. Synchrobreathe^® is an easy-to-use, breath-actuated inhaler that releases medication during inhalation, addressing these challenges. Although its use in asthma is well documented, evidence in COPD is limited.

Methods: This prospective, multicenter, observational study carried out during August 2021 and August 2022 evaluated the clinical outcomes of the budesonide/formoterol combination (BUD/FORM) delivered through Synchrobreathe^® in patients with COPD in India. The primary endpoint was disease control, that is, change from baseline in COPD Assessment Test (CAT) score at 12 weeks. Secondary endpoints included changes in CAT and modified Borg Dyspnea Scale (mBDS) scores and device usability. Adverse events were monitored over 12 weeks.

Results: In the study population (N = 250), significant reductions from baseline were observed in mean CAT (-6.56 ± 0.33; p < 0.001) and mBDS (-1.60 ± 0.09; p < 0.0001) scores at 12 weeks. Almost all (98%) patients were satisfied with Synchrobreathe^® and preferred it over their previous inhalers. No significant adverse events were reported.

Conclusion: BUD/FORM delivered through Synchrobreathe^® significantly improved CAT and mBDS scores, with no reported serious adverse events in patients with COPD. Its simple usage makes it an effective option for this patient population.

Background: Paroxysmal nocturnal haemoglobinuria (PNH) is a chronic haematological disorder caused by uncontrolled complement activation, leading to intravascular haemolysis, indicated by increased lactate dehydrogenase levels (LDH). Standard-of-care complement factor 5 inhibitors have only recently been approved in China. Using real-world data, this study aimed to understand treatment pattern and burden of disease, including thrombosis risk, for Chinese patients with PNH.

Methods: Data were from the Adelphi Real World PNH Disease Specific Programme (DSP)™, a cross-sectional retrospective survey of haematologists/haematologist-oncologists and patients with PNH, conducted July-November 2022. Physicians reported demographic and clinical data on one to ten consecutively consulted patients with PNH aged ≥ 16 years. Patients were stratified by LDH level [cutoff of 1.5 times upper level of normal (ULN, 250 U/L)] and compared using bivariate analysis.

Results: Out of 113 patients, 49.5% had LDH levels ≥1.5 ULN (high-LDH), these had greater physician-perceived disease severity (p<0.001). Anticoagulation treatments (39.8%), prednisone (31.0%), and cyclosporine (27.4%) were most prescribed. More high-LDH patients received rivaroxaban (p=0.002) or vitamin B12 supplements (p=0.008). Overall, the most common symptoms were fatigue and anaemia (92.9% and 74.3%, respectively). Haemolytic crises were reported for 39.3% of all patients, thrombotic events were more common in high-LDH patients (50.0%, compared with 23.2%, p=0.006). Patients reported moderate fatigue levels in the FACIT-Fatigue scale.

Conclusions: Patients were mainly treated with anticoagulants, prednisone or cyclosporine, and had frequent thrombotic events and haemolytic crises. This demonstrates the current management of PNH in China, focusing on mitigating anaemia and managing haemolytic crises rather than addressing the underlying chronic complement-mediated haemolysis and associated morbidities.

Background: The administration of antineoplastic agents to pregnant women requires comprehensive evaluation of fetal risks and therapeutic benefits for the mother. In Japan, there has traditionally been a tendency to uniformly classify such cases as 'contraindicated' when reproductive toxicity data are insufficient. However, a shift toward a more flexible policy has occurred since the approvals of daratumumab and pembrolizumab in 2017.

Objective: This study quantitatively evaluated the changes in regulatory decisions regarding the administration of antineoplastic agents to pregnant women approved by the Ministry of Health, Labour and Welfare (MHLW) following review by the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan since October 2004 to identify influencing factors and compare decision trends with those of the US Food and Drug Administration (FDA).

Methods: A total of 129 drugs approved by the PMDA and FDA were analyzed. The evaluation included classification of decisions (contraindicated, warning, benefit-based administration), annual trends (Joinpoint regression), and background factors (logistic regression).

Results: Since 2018, the proportion of drugs judged as 'benefit-based administration' increased to 82.5%. Significant positive associations were observed between benefit-based administration and the following predictors:more recent PMDA approval year, monoclonal antibody drug modality (vs small molecules), absence or presence offetal death, and absence or presence of reversible alterations. Fetal growth retardation showed a negative association with benefit-based administration; 'unassessable' classifications tended to act as a barrier to decision making. The concordance rate with the FDA was only 12.4%, suggesting systematic differences in decision-making approaches.

Conclusion: In recent years, the PMDA has adopted a more flexible approach that prioritizes clinical benefit. Importantly, the presence of assessable information-rather than the absence or presence of risk-was identified as a key factor influencing regulatory decisions. However, this descriptive comparison did not restrict the sample to clinically similar drugs. Therefore, while the observed differences likely reflect regulatory tendencies to some extent, they may also be partially influenced by differences in drug background characteristics.

Background: Acetaminophen is a commonly used analgesic and antipyretic. In South Korea, a 2012 regulatory change allowed its over-the-counter sale in convenience stores, increasing public accessibility.

Objectives: We aimed to assess the impact of increased over-the-counter availability of acetaminophen on adolescent self-poisoning trends in South Korea.

Methods: This population-based observational study used the National Health Insurance Service customized database to analyze trends in acetaminophen-related poisoning among adolescents before and after the 2012 policy change. Age-specific trends were evaluated, and poisoning episodes were categorized by recurrence and severity.

Results: Following the policy change, the number of acetaminophen poisoning cases increased from 2.4 to 3.8 (during 2007-11 and 2013-17, respectively, per 100,000 adolescents). This increase was particularly significant among adolescents aged 16-18 years, rising from 10.7 to 23.8 per 100,000 (p < 0.05). While the total number of poisoning events increased, the number of affected individuals remained largely unchanged (86.4 vs 80.0), suggesting a more frequent recurrence. The proportion of acetaminophen poisonings among all drug poisoning cases increased from 5.2% to 9.7%, whereas the increase in the proportion of severe cases requiring hospitalization was relatively modest.

Conclusions: The findings suggest that increased over-the-counter availability of acetaminophen may be associated with a rise in misuse among older adolescents. Public health measures, including stricter over-the-counter regulation and targeted interventions, may be needed to mitigate the risk of self-harm in this population.

Background: Older adults are under-represented in clinical trials investigating spondyloarthritis (SpA), limiting the generalizability of efficacy and safety data for this population. In this context, real-world evidence on drug retention and treatment discontinuation is essential to guide long-term therapeutic decisions, particularly for biologic disease-modifying antirheumatic drugs (bDMARDs) and apremilast.

Objectives: This study aimed to assess the 24-month retention rates of bDMARDs and apremilast in patients aged ≥ 60 years with SpA.

Methods: This was a single-center, observational study conducted over 24 months at Azienda Ospedaliero-Universitaria Policlinico "Gaspare Rodolico - San Marco" Catania. Patients aged ≥ 60 years with SpA, classified according to the Assessment of Spondyloarthritis International Society (ASAS) or the ClASsification criteria for Psoriatic ARthritis (CASPAR) criteria, were included if they initiated bDMARD or apremilast therapy during the study period. The primary outcome was bDMARD and apremilast retention at 6, 12, and 24 months. Kaplan-Meier survival analysis was used to assess drug retention, and reasons for discontinuation were analyzed.

Results: A total of 100 patients (66% female; mean age 64.17 ± 0.48 years) were included. Retention rates declined progressively, with 42% remaining on their initial therapy at 24 months. The most common reasons for discontinuation were adverse events (48%) and lack of efficacy (35%). Interleukin-17 (IL-17) inhibitors, particularly secukinumab, demonstrated superior retention compared with TNF-α inhibitors in patients with prior biologic failures.

Conclusions: Retention of bDMARDs and apremilast in older SpA patients declines over time, with adverse events and inefficacy as key discontinuation drivers. IL-17 inhibitors exhibited better retention, suggesting a potential advantage in this population. Given the impact of comorbidities and treatment safety, personalized treatment strategies and further real-world studies are needed to optimize care in older SpA patients.

Background: The cost burden of new-onset atrial fibrillation (AF) has not previously been studied with unselected nationwide data.

Objective: We analyzed differences in the distribution and time course of costs from all categories of healthcare services in patients receiving direct oral anticoagulants (DOACs), warfarin, or no anticoagulation during the first year following diagnosis of AF.

Methods: This sub-study of the Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) project comprised all new-onset AF patients from 2011 to 2017 in Finland with an indication for oral anticoagulation treatment. The registry data included information on primary and secondary care services as well as social care services, drug purchases, laboratory data, and reimbursed private care and travel services. We report inverse probability of treatment weighted average costs for different pharmaceutical groups with bootstrapped confidence intervals.

Results: In total, 130,745 patients (66,610 on warfarin, 32,996 on DOACs) were included. Weighted first-year costs after onset of AF were €11,364 for rivaroxaban (n = 13,230), €12,642 for apixaban (n = 11,886), €11,403 for dabigatran (n = 7514), and €10,752 for edoxaban (n = 366). Costs were clustered near the diagnosis of AF. Costs for warfarin patients were inversely related to the quality of anticoagulation therapy. Average first-year costs for warfarin patients were €15,860, higher than for patients on DOACs by €3218-€5108. Patients without any oral anticoagulation had the highest first-year costs, €17,682. Patients with high risk of stroke had higher total costs, both in patients using DOACs and warfarin.

Conclusions: DOACs had lower total costs than warfarin despite higher drug expenses. Patients without any oral anticoagulation had the highest costs.

Clinicaltrials identifier: NCT04645537.

Encepp identifier: EUPAS29845.

Introduction: People with hemophilia A (PwHA) may suffer from repeated bleeding in muscles and joints. However, few studies have reported disease burden and healthcare resource utilization (HCRU) in PwHA experiencing bleeding events and/or joint disorders in a real-world setting. The aim of this study was to examine disease burden and HCRU in PwHA via two different categorizations: PwHA with and without medically recorded bleeding (MRB), and PwHA with and without joint disorders.

Methods: This was an observational cross-sectional study of adult male PwHA treated with factor VIII replacement therapy, identified from PharMetrics Plus^® claims data between 2010 and 2019. Comorbidities prevalence and HCRU rates were described. Rate ratios (RRs) of HCRU between PwHA with and without MRB, and PwHA with and without joint disorders were estimated using multivariate adjusted Poisson or negative binomial regressions.

Results: There were 1961 PwHA identified. Of those, 1045 had MRB and 352 had arthropathy. PwHA with MRB showed a higher prevalence of comorbidities and HCRU compared with those without MRB, including inpatient admissions, emergency department visits, outpatient visits, factor VIII replacement therapy, and pain relief medications use. PwHA with MRB also had high bleeding-related HCRU; bleeding-related events accounted for 46% of inpatient hospitalizations. Similarly, PwHA with joint disorders had a higher comorbidity burden and HCRU than those without joint disorders.

Conclusions: PwHA with concurrent bleeding/joint disorders had higher clinical burden compared with those without MRB or joint disorders. Treatment approaches to reduce bleeding episodes, and consequently joint damage, in PwHA may reduce clinical burden.