Drugs - Real World Outcomes最新文献

Background and objectives: Extended follow-up data from real-world cohorts of patients with multiple sclerosis treated with ocrelizumab (OCR) are becoming widely available. This monocentric retrospective study aimed to evaluate the long-term effectiveness of OCR and its impact on immunoglobulin (Ig) levels, lymphocyte subsets, and infections in a cohort of patients with relapsing remitting, primary progressive, and secondary progressive multiple sclerosis.

Methods: Patients followed at the Multiple Sclerosis Center of Bari with ≥ 2 years of OCR treatment were retrospectively recruited in 2024. Twelve-month confirmed disability worsening, improvement, and the annualized relapse rate before and after treatment start were estimated and follow-up magnetic resonance imaging scans were collected. Changes in IgG/IgM/IgA levels from baseline for up to 6 years of OCR treatment and serum levels of T CD4+, T CD8+, and natural killer lymphocytes were assessed. Infection occurrence, type, and outcomes were investigated. Multivariable Cox models examined the association of clinical and radiological baseline factors with the risk of confirmed disability worsening and the relationship of infections with clinical-laboratoristic risk factors.

Results: The final cohort retrieved 140 patients (80 relapsing remitting, 37 primary progressive, 23 secondary progressive) with a median (interquartile range) follow-up after treatment start of 4.62 (4.10-5.04) years. In the entire cohort, the mean annualized relapse rate decreased from 0.61 in the year before the start of OCR treatment to 0.02 in the second year, thereafter all patients in our cohort remained free of relapses and magnetic resonance imaging activity. The overall percentage of stable patients increased from the second to the fourth year, in parallel with a reduction in patients with confirmed disability worsening. A multifocal onset and the presence of at least two relapses before the start of OCR treatment were significant (p < 0.05) risk factors of confirmed disability worsening. During the follow-up, a reduction in the IgG serum level was observed, which further decreased, becoming stable after the third year. Immunoglobulin M levels slightly decreased over time, whereas IgA levels remained stable. No changes for T CD4+, natural killer cell absolute number, and a slight reduction in T CD8+ lymphocytes during follow-up were observed. Ocrelizumab did not determine a significant infection risk in the long term and no association was observed with Ig levels and severe infections.

Conclusions: Ocrelizumab prevented disease activity over the long term and its effect on the immune system did not determine a significant infection risk in most patients.

Background: The advent of biologics has expanded treatment options for Crohn's disease (CD). This study assessed treatment patterns in pediatric and adult patients with CD in the United States during 1- and 3-year follow-up periods.

Methods: This retrospective, claims-based cohort study utilized the Merative™ MarketScan^® Research Databases from January 1, 2014, to December 31, 2021. The index date was the date of the first CD diagnosis during the identification period. Among pediatric and adult CD cohorts, patients were stratified into two subgroups: (a) previously diagnosed (presence of a CD claim) and (b) newly diagnosed (absence of a CD claim) in the 12-month pre-index period. Results were summarized descriptively.

Results: Data from 2809 pediatric and 25,940 adult patients were analyzed at 1-year follow-up. Mean age in years was 13.5 for pediatric and 46.0 for adult patients. Combination therapies were more common in pediatric versus adult patients, especially among those newly diagnosed with CD (38.2% vs 13.9%). A higher percentage of pediatric patients were prescribed biologics than adults (35.1% vs 24.3%). Numerically shorter time from diagnosis to corticosteroid initiation was observed in pediatric versus adult patients (9.5 vs 35 days). Higher persistence to biologics was observed in pediatric versus adult patients (94.6% vs 87.1%).

Conclusions: Combination therapies with biologics were more frequent among pediatric patients than adults. Although the overall treatment pattern among pediatric and adult patients was similar, early initiation of corticosteroids and adoption of biologics were more frequently observed in pediatric than adult patients, consistent with pediatric CD presenting with more aggressive disease.

Introduction: High levels of low-density lipoprotein-cholesterol (LDL) is a major risk factor for cardiovascular diseases. While treatment with atorvastatin is beneficial, the original atorvastatin may be cost prohibitive to some patients. Currently, a second brand of generic atorvastatin is available on the market. This study aimed to evaluate the effectiveness of the second generic brand of atorvastatin.

Methods: This was a retrospective cohort study conducted at Khon Kaen University Hospital, Thailand. The inclusion criteria were adult patients who received either Xarator^® (original atorvastatin; Pfizer Pharmaceuticals, Puerto Rico) or Atorvastatin Sandoz^® (Lek Pharmaceuticals, Slovenia) for at least 3 months prior to switching therapy to the second brand: Lipostat^® (Siam Pharmaceutical, Thailand). The study period was between 1 April 2022 and 30 June 2023. The primary outcome of this study was a change in LDL 6 months after switching therapy from either the original (Xarator^®) or generic atorvastatin (Atorvastatin Sandoz^®).

Results: There were 683 patients who switched therapy from the original atorvastatin (Xarator^®), and 1044 patients who switched therapy from generic atorvastatin (Atorvastatin Sandoz^®), for a total of 1727 patients. Regarding LDL levels, switching therapy from original atorvastatin (Xarator^®) resulted in a slightly lower but not significant decrease in LDL at 6 months (- 0.96 mg/dL; 95% CI of - 3.20, 1.28), while switching therapy from generic atorvastatin (Atorvastatin Sandoz^®) led to significantly lower LDL at - 3.30 mg/dL (95% CI of - 5.25, - 1.36). The original (Xarator^®) and generic atorvastatin (Atorvastatin Sandoz^®) group also resulted in a significantly lower estimated glomerular filtration rate at - 0.90 and - 1.21 mL/min/1.73 m², respectively, from baseline.

Conclusions: The second generic atorvastatin (Lipostat^®) resulted in comparable outcomes on LDL compared with the original (Xarator^®), but significantly lower LDL levels than another generic atorvastatin (Atorvastatin Sandoz^®) 6 months after switching therapy. However, renal function should be closely monitored.

Background: In pulmonary arterial hypertension (PAH), comparative assessment of treatment effect on survival in randomized controlled settings of contemporary patients has not been feasible.

Objective: The aim of this study was to use EXPOSURE, the ongoing, real-world, post-authorization safety study, and commitment to the European Medicines Agency to perform pre-specified comparative survival analyses between patients that newly initiated selexipag versus other PAH-specific therapies by applying statistical methods to account for population differences.

Methods: EXPOSURE (EUPAS19085) is an observational study comprising patients with PAH who initiated selexipag or other PAH-specific therapy. To balance characteristics of patients in the other PAH therapy cohort with the selexipag cohort at PAH therapy initiation (baseline), propensity score weighting was applied. Mortality rate ratios (MRRs) were calculated.

Results: 2014 patients were available for analysis. Prior to applying propensity score weighting, patients in the selexipag cohort were more likely to have longer time from diagnosis, less functional impairment, and treatment with combination background therapy versus the other PAH therapy cohort. Following weighting, baseline variables for both cohorts were well balanced. Weighted treatment exposure was 827.9 and 840.5 person-years for the selexipag and modelled other PAH therapy cohort, respectively. Weighted proportion of deaths was lower in the selexipag versus modelled other PAH therapy cohort; MRR showed a higher survival rate for selexipag-treated patients (MRR [95% confidence interval]: 0.55 [0.31-0.99]).

Conclusions: Survival analyses in EXPOSURE suggest a reduced risk of mortality among the cohort of patients newly initiated on selexipag compared with the modelled cohort newly initiated with other PAH-specific therapies. Further research is needed to confirm this observation.

Trial registry: Trial registration: EUPAS19085.

Background: The humanized anti-disialoganglioside-2 monoclonal antibody naxitamab was approved in the USA in 2020 for the treatment of patients with relapsed/refractory high-risk neuroblastoma, limited to the bone or bone marrow, in combination with granulocyte-macrophage colony-stimulating factor. Treatment with naxitamab under expanded access was initiated by physicians from the Children's Hospital of Fudan University, Shanghai, China, in August 2021.

Objective: We reviewed all suspected adverse reactions (ARs) reported to the Y-mAbs Argus Global Pharmacovigilance Safety Database for patients treated with naxitamab under expanded access in China from 1 August 2021 to 31 July 2022.

Methods: We assessed patient demographics and the safety profile of naxitamab over multiple treatment cycles.

Results: At the data cutoff, 41 patients with relapsed/refractory high-risk neuroblastoma had received a total of 150 treatment cycles (451 infusions) of naxitamab. The median number of cycles completed was three; 13 patients (32%) were receiving ongoing naxitamab treatment. The median patient age was 3 years (range 1-9 years) and 63% were female. Overall, ARs were reported in 89/150 cycles (59%); serious ARs were reported in 23/150 cycles (15%). The cumulative reporting rate (ARs/cycle) decreased after 3 versus 12 months of expanded access: all ARs (8.7-4.6), serious ARs (0.9-0.3), hypotension (1.4-1.0), flushing (0.7-0.5), cough (0.6-0.3), pain (0.5-0.2), and hypoxia (0.3-0.2).

Conclusions: During the first 12 months of expanded access treatment in China, 41 patients received naxitamab therapy with a cumulative 451 infusions administered. Over the course of this expanded access program, a reduction in the AR rate, including serious ARs, was observed as more patients were initiated and proceeded to later treatment cycles. While additional research is needed, the observed decrease in the AR rate may be attributed to clinicians' increased knowledge of AR management and hands-on experience with naxitamab-treated patients.

Background and objective: Vildagliptin sustained release (XR), a formulation that provides vildagliptin 100 mg with a once-daily dose administration, is a recent introduction to manage type 2 diabetes mellitus in India. This study aimed to evaluate the effectiveness and tolerability of vildagliptin XR in patients with type 2 diabetes in real-world clinical settings.

Methods: This was an observational, prospective, multicenter, cohort study conducted in India, which included patients with type 2 diabetes uncontrolled on metformin XR monotherapy with glycated hemoglobin (HbA1c) > 7.00%. Vildagliptin XR was added to their ongoing treatment. The primary endpoint was a change in HbA1c from baseline to 3 months. Secondary endpoints were changes in fasting plasma glucose, postprandial plasma glucose, percentage of patients achieving HbA1c < 7.00% at 3 months, and assessment of efficacy, tolerability, and safety.

Results: A total of 1691 patients from 118 centers were enrolled in this study, having a mean (standard deviation) age of 53.10 (11) years and a mean (standard deviation) HbA1c of 8.44 (1.35) %. At the end of the study, vildagliptin XR significantly reduced the mean HbA1c by 1.02% points (95% confidence interval 0.93-1.12; p < 0.001) from baseline. The mean fasting plasma glucose and postprandial plasma glucose levels were significantly reduced by 28.44 mg/dL (95% confidence interval 26.64-30.25; p < 0.001) and 48.45 mg/dL (95% confidence interval 45.91-50.99; p < 0.001), respectively, with vildagliptin XR, at the end of study. During the study duration, 34.7% of patients achieved their glycemic target (HbA1c < 7.0%) and there were three reported adverse events (all mild in severity).

Conclusions: Results demonstrated that vildagliptin XR (100 mg once daily) significantly improved HbA1c and other glycemic parameters in Indian patients with type 2 diabetes and was well tolerated.

Clinical trial registration: The study was registered under the Clinical Trials Registry India (CTRI/2022/01/039112).

Anti-seizure medications (ASMs) are specific types of anticonvulsants used to treat epileptic seizures. However, several studies have shown an association between ASMs and an increased risk of hematological disorders, such as thrombocytopenia, aplastic anemia, and platelet function disorders leading to prolonged bleeding times. This review explores the existing literature on this topic, investigating a wide variety of ASMs, ranging from first-generation medications to newer ones. A comprehensive search was conducted on all the currently approved ASMs using PubMed and Google Scholar: review articles, clinical trials, meta-analysis, observational studies, case reports, and relevant animal studies were identified. We extracted 15 ASMs including valproic acid (VPA), carbamazepine, phenytoin, phenobarbital, diazepam, clonazepam, lamotrigine, levetiracetam, oxcarbazepine, felbamate, topiramate, pregabalin, lacosamide, cannabidiol (CBD), and perampanel that contain considerable literature regarding different coagulopathies. An in-depth review of over 140 studies revealed a robust association between ASM-induced changes and the onset of bleeding disorders via several different mechanisms. Polytherapy, the use of multiple ASMs, also emerged as a significant risk factor for the development of coagulopathies. This review highlights the potential link between ASMs and bleeding disorders, emphasizing the importance of considering this risk during treatment planning. By understanding these associations, healthcare providers can optimize patient outcomes and minimize bleeding risks. Additionally, this review identifies the need for further research to bridge current knowledge gaps in clinical pharmacology related to ASMs and bleeding disorders.

Background: Lanadelumab is the only long-term prophylaxis indicated for reduced administration frequency in patients with hereditary angioedema who have been well controlled for > 6 months. Understanding the characteristics of patients who reduce administration frequency will help identify populations where frequency modifications may be appropriate.

Objective: We aimed to describe characteristics of patients who did and did not reduce lanadelumab administration frequency to inform real-world dosing regimens, and characteristics indicative of sustained frequency reduction.

Methods: A retrospective observational study using healthcare insurance data in the USA from the Merative™ MarketScan^® Commercial and Medicare Databases identified patients persistent on lanadelumab for ≥ 18 months. Reduced administration frequency was defined as a ≥ 25% decrease in lanadelumab costs during months 7-12 or 13-18 versus 0-6. Hereditary angioedema attack triggers/symptoms and hereditary angioedema-related healthcare encounters, treatment, and costs were assessed.

Results: Of 54 identified patients, 25 reduced administration frequency. Two patients returned to initial dosing frequency during months 13-18 after reducing during months 7-12. Patients who reduced administration frequency experienced fewer hereditary angioedema attack triggers/symptoms before lanadelumab initiation (baseline) and during months 0-6 than those who did not; they also had a lower mean number of hereditary angioedema-related inpatient admissions, emergency room visits, and outpatient visits during baseline, had fewer claims for acute treatment (60.0% vs 65.5%) and prior long-term prophylaxis (20.0% vs 27.6%), and had lower mean hereditary angioedema treatment costs at baseline ($139,520 vs $233,815) than those who did not.

Conclusions: This real-world analysis suggests that patients with less frequent hereditary angioedema-related healthcare encounters, lower disease activity, and lower costs within 6 months before lanadelumab initiation are more likely to achieve reduced dosing frequency.

Introduction: This study aimed to investigate the association between the 2023 Beers criteria for inappropriate prescribing and different health outcomes among community-dwelling older individuals after a 1-year follow-up period and to assess the use and factors associated with inappropriate prescribing.

Methods: This longitudinal population study spanning from 2017 to 2018 included 490 community-dwelling older adults (≥60 years old) receiving care from family medicine teams in the city of São João del-Rei, Brazil. The 2023 Beers criteria was used to identify potentially inappropriate medications (PIMs). Community health workers carried out interviews assessing different health outcomes, such as cognition, sleep, mental health, quality of life, successful aging, and life satisfaction. Generalized estimating equations were used to evaluate whether the presence of PIMs was longitudinally associated with diverse outcomes following the 1-year follow-up period.

Results: A total of 255 (52%) of the participants used at least one PIM. The most common PIMs were benzodiazepines (36.5-38.3%), followed by proton pump inhibitors (16.2-18.4%) and sulfonylureas (9.8-10.6%). Some sociodemographic factors (e.g., marital status and race) and clinical factors (e.g., difficulties in activities of daily living and the number of diseases) were associated with the presence and/or number of PIMs at baseline. In the longitudinal analysis, the presence of PIMs exhibited associations with a spectrum of outcomes observed after a 1-year follow-up period. These outcomes included diminished physical quality of life (B = -0.21; p = 0.030), disrupted sleep patterns (B = 1.14; p < 0.001), compromised mental health-depression (B = 1.04; p = 0.041), stress (B = 2.00; p = 0.001), and anxiety (B = 1.26; p = 0.004), successful aging (B = -1.92; p = 0.033), and satisfaction with life (B = -0.77; p = 0.013).

Conclusion: The use of at least one PIM, according to the 2023 Beers criteria, was high and associated with worse health outcomes. This underscores the imperative for healthcare professionals to exercise caution when prescribing medications to older patients.

Background: In October 2016, precautions of the package inserts for ethical drugs containing statins were revised for immune-mediated necrotizing myopathy (IMNM).

Objective: Our objective was to assess the trend in statin-associated IMNM reported before and after the release of the revised precautions in Japan.

Methods: We investigated the number of case reports and estimated annual incidence rate of statin-associated IMNM using the Japanese Adverse Drug Event Report and Japan Medical Data Center (JMDC) databases, respectively. To identify IMNM case reports, we used the preferred term "immune-mediated myositis" (MedDRA version 27.1).

Results: We identified 172 statin-associated IMNMs in 145 case reports of patients between 1 April 2004 and 31 March 2023. The most common suspected statin administered to the patients was rosuvastatin (34.3%), followed by pitavastatin (25.0%) and atorvastatin (22.1%). No statin-associated IMNM was reported in patients who were treated with combination agents containing statins. The number of reported statin-associated IMNMs increased from 3 in 2015 to a peak of 51 in 2019, after which it was 22 (2020), 17 (2021), and 21 (2022) in the following years. The estimated annual incidence rate did not differ with statins, it rarely exceeded 5 per 1,000,000 patients.

Conclusions: There was an increasing trend in the number of statin-associated IMNM after the revised precautions of package inserts for statins were released.