Drugs - Real World Outcomes最新文献

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.

Background: Increasing global frequency of drug-induced interstitial lung disease (ILD) coincides with increasing market introduction of tyrosine kinase inhibitors (TKIs).

Objectives: The aim was to detect disproportional reporting of TKI-induced ILD in the EudraVigilance post-marketing safety database and to scrutinise the prescribing information of these TKIs.

Methods: Data were gathered on the number of total and individual ILD case safety reports for each TKI marketed in the European Union (EU), together with indications and patient demographics. Information was also obtained on numbers of total and ILD reports for all drugs in the entire database, covering the period January 2002 to March 2024. Chi-squared analyses and two measures of disproportionality, the proportional reporting ratio (PRR) and reporting odds ratio (ROR), were used to ascertain the ILD-inducing potential of TKIs, both as a group and with each TKI individually. The latest prescribing information for each TKI was evaluated for ILD-related information.

Results: TKIs were collectively associated with a significantly stronger disproportionality signal for ILD reports compared to all non-TKI drugs (p < 0.001). There was marked variation in the disproportionality of ILD reporting across the 51 TKIs studied. Potential risk factors included male gender (p < 0.001), age 65-85 years (p < 0.001) and an oncological indication (p < 0.001), particularly non-small cell lung cancer (NSCLC). Fatality rates among cases of TKI-induced ILD were 17.4% overall, 22.2% in patients with NSCLC and 11.5% in those with a non-oncological indication. The prescribing information of 11 TKIs lacked any reference to ILD despite a strong signal that indicated their potential association with ILD.

Conclusions: Drug-induced ILD is emerging as an important safety issue, and physicians need to maintain a high index of suspicion of ILD in patients treated with a TKI.

Background: Semaglutide is an effective antidiabetic agent that is injected weekly to induce weight reduction, and the impact on cardiovascular outcomes is favorable.

Objective: The aim was to evaluate the persistence of the use of weekly injectable semaglutide in Colombia for 12 months among new users.

Methods: A retrospective longitudinal follow-up study of a cohort of patients with a new prescription of weekly injectable semaglutide between January and December 2022 and persistence for 365 days was evaluated. Kaplan‒Meier survival analyses were performed to evaluate the survival effect of semaglutide.

Results: In total, 9356 new users of semaglutide were identified. The average age of the users was 61.6 ± 12.9 years, the main diagnoses were type 2 diabetes mellitus (43.8%) and obesity (41.8%), and 90.8% of them received the 0.25/0.5-mg dose. The mean duration of use was 93.7 ± 76.3 days, but only 13.8% and 0.2% of patients continued the treatment at 6 and 12 months of follow-up, respectively. In total, 35.4% had a prescription for a single month. The other concomitant antidiabetic drugs used were metformin (43.5%), sodium glucose-2 cotransporter inhibitors (38.3%) and insulin (18.2%).

Conclusions: Most of the patients started semaglutide at the suggested doses to continue with staging; however, the persistence of use was low, which may be related to difficulties in access, education on application methods, drug tolerability, and lack of follow-up by the clinician.

Background: Psoriatic disease (PsD) is a chronic, multisystem, inflammatory disorder encompassing psoriasis, psoriatic arthritis (PsA), and their associated comorbidities.

Objective: The aim of this subanalysis of the global "Psoriasis and Beyond" study was to evaluate patients' experiences of living with PsD in the USA.

Methods: The study included a cross-sectional, quantitative, 25-min online survey of adults with self-reported, healthcare professional-diagnosed, moderate-to-severe psoriasis, with or without PsA. USA-based patients were recruited through online panels by the Institut de Publique Sondage D'Opinion Secteur and The National Psoriasis Foundation.

Results: This analysis included 793 US patients with psoriasis; 43% also had PsA. Overall, 75% of patients knew that their disease was systemic, and 65% had heard the term "psoriatic disease." Of patients without diagnosed PsA, 50% screened positive for PsA using the Psoriasis Epidemiology Screening Tool. Psoriasis negatively affected emotional well-being and quality of life (QoL) in the majority of patients (87% and 91%, respectively). Overall, 29% of patients reported that they could not work or study in the week prior to the survey; of these, 98% responded that psoriasis had a very or extremely large impact on their QoL. Mean diagnostic delays of 3.7 and 3.3 years for psoriasis and PsA, respectively, were reported.

Conclusions: This analysis of USA-based patients with PsD highlights the profound impact of PsD on emotional well-being and QoL and suggests potential underdiagnosis of PsA. There is a need to ensure early PsD diagnosis and to provide holistic treatment, including mental health support.