Drugs - Real World Outcomes最新文献

Background: Parkinson's disease is now one of the fastest-growing neurodegenerative disorders in the developed world, with an increasing prevalence and associated socioeconomic costs. Progression of the disease leads to a gradual deterioration in patients' quality of life, despite optimal treatment, and both medical and societal needs increase, often with the assistance of paid and/or unpaid caregivers.

Objective: We aimed to quantify the incremental economic burden of Parkinson's disease by disease severity in a real-world setting across differing geographic regions.

Methods: Demographics, clinical characteristics, health status, patient quality of life, caregiver burden, and healthcare resource utilization data were drawn from the Adelphi Parkinson's Disease Specific Program™, conducted in the USA, five European countries, and Japan.

Results: A total of 563 neurologists provided data for 5299 individuals with Parkinson's disease; 61% were male, with a mean age of 64 years. Approximately 15% of individuals were deemed to have advanced disease, with significantly more comorbidities, and a poorer quality of life, than those with non-advanced disease. Overall, the mean annual healthcare resource utilization increased significantly with advancing disease, and resulted in a three-fold difference in the USA and Europe. The main drivers behind the high economic burden included hospitalizations, prescription medications, and indirect costs.

Conclusions: People with Parkinson's disease, and their caregivers, incur a higher economic burden as their disease progresses. Future interventions that can control symptoms or slow disease progression could reduce the burden on people with Parkinson's disease and their caregivers, whilst also substantially impacting societal costs.

Background: In Japan, daily, twice weekly, and weekly formulations of teriparatide (TPD) and monthly formulations of romosozumab (ROMO) are available as osteogenesis promoters for the treatment of osteoporosis with a high risk for fracture.

Objective: To compare the effects of three TPD preparations and ROMO on fracture healing and low back pain after a fresh vertebral fracture.

Methods: This was a retrospective observational study. Patients presenting with fresh osteoporotic vertebral fractures were treated subcutaneously with TPD daily (DTPD), twice weekly (2/WTPD), weekly (WTPD), or with ROMO monthly. Bone union, vertebral height changes, and low back pain in the injured vertebra were compared after 6 months of treatment.

Results: Bone union and pain improvement were more frequent among those who received daily and twice weekly administration of TPD compared with those who received WTPD and ROMO administration. A comparison for multiplicity between the groups using the Steel-Dwass test showed significant differences between the DTPD and ROMO groups (p = 0.0029) and WTPD and ROMO groups (p = 0.0490), suggesting superior bone fusion in the DTPD and WTPD groups. Similarly, significant differences were noted between the DTPD and ROMO groups (p = 0.0001), WTPD and ROMO groups (p = 0.0341), and 2/WTPD and ROMO groups (p = 0.0009), indicating a higher degree of pain improvement in the DTPD, WTPD, and 2/WTPD groups compared with that in the ROMO group.

Conclusions: Daily, weekly, and twice-weekly administration of TPD may be superior to ROMO for promoting fresh vertebral fracture healing.

Background: Cabozantinib was found to be effective as a second- or third-line treatment after sorafenib in patients with advanced hepatocellular carcinoma (HCC) in the phase 3 CELESTIAL trial. So far, as immunotherapy has substituted molecular target agents as the primary systemic therapy for advanced HCC, cabozantinib is extensively used in the latest real-world clinical practice in a greatly different position than that shown by the CELESTIAL trial. In the current analysis, we examined the safety and effectiveness of cabozantinib administration in real-life settings for patients with advanced HCC.

Methods: We retrospectively obtained data from patients with advanced HCC who received cabozantinib in three institutions in Japan between 14 September 2018 and 30 November 2021.

Results: During the study period, 23 patients with advanced HCC received cabozantinib. Our cohort included 21.7% of patients with Child-Pugh class B, and 52.2% of patients in fourth line or later. The median progression-free survival of patients given cabozantinib was 3.7 months. Regarding patients with Child-Pugh class B or administration in fourth line or later, the discontinuation rate due to adverse events in patients who initialized at 40 or 20 mg was lower than those who initialized at 60 mg (42.9% versus 75.0%). Patients who were able to continue treatment with cabozantinib for more than 3 months were more likely to undergo dose reduction than those who did not (85.7% versus 25.0%).

Conclusions: Cabozantinib has recently been administered to a diverse range of patients, including those who were not enrolled in the CELESTIAL trial. Deliberate dose reduction could potentially offer clinical benefits to patients with impaired liver function. Furthermore, managing adverse events by reducing the dose could play a crucial role in extending the duration of treatment with cabozantinib. The preprint version of this work is available on https://www.researchsquare.com/article/rs-2655181/v1 .

Background: Irritable bowel syndrome (IBS) is a functional disorder that leads to abdominal pain; its diagnosis is based on Rome IV criteria (recurrent abdominal pain at least 1 day per week in the last 3 months with more than two of the following: related to defecation, associated with a change in stool frequency and/or with a change in stool appearance).

Objective: To characterize an outpatient population diagnosed with IBS in Colombia during 2017-2018.

Methods: A cross-sectional study based on a review of clinical records of patients with a primary diagnosis of IBS. A representative sample of 380 individuals was recruited from a population of 38,182 people with a new diagnosis of IBS from a drug-claim database. Sociodemographic, clinical (symptoms, type of IBS, alarm features, etc.), treatment (pharmacological or not), and follow-up variables (for those with additional medical care at 3-12 months) were analyzed. The diagnosis and treatment used in the consultation were compared with clinical guidelines.

Results: Most of the 380 patients were women (n = 238; 62.6%), and the mean age was 40.1 ± 15.0 years. None of the physicians recorded the Rome IV criteria in the medical records. Unclassified IBS was the most prevalent subtype (n = 311; 81.8%), and the main symptom was abdominal pain (n = 327; 86.1%). Only 73 patients (19.2%) had follow-up data. The most frequently used drugs were aluminum hydroxide (n = 203; 53.4%) and hyoscine N-butyl bromide (n = 200; 52.6%). Regarding drugs included in the clinical practice guidelines, 19 people received loperamide (5.0%), 3 received trimebutine (0.8%), and 1 received sertraline (0.3%).

Conclusions: The patients were diagnosed without clearly established criteria, and they were treated symptomatically with little follow-up.

Background: Several oral drugs are recommended to be taken with large amounts of water for reasons such as peptic ulcer prophylaxis. On the other hand, there are many patients with diseases that restrict water intake, and the actual frequency of patients receiving prescriptions in these conflicting situations is not clear.

Objective: Using a large claims database in Japan, this study aimed to determine the proportion of patients aged ≥ 75 years on fluid restriction who received drugs whose drug package insert mentioned "a large amount of water intake is needed when taking the drug".

Methods: We performed a prescription survey of older patients over 75 years of age using the Japan Medical Data Centre (JMDC) claims database. Out of approximately 8800 oral drugs used in Japan, we defined 29 drugs for which package inserts noted that a large amount of water intake is recommended during drug administration. We defined diagnosis codes for some common diseases for which restricted water intake is likely recommended: heart failure (NYHA class III or IV), liver cirrhosis with ascites, and chronic kidney disease stage 5, including dialysis patients.

Results: Of 5968 patients aged ≥ 75 years (men 47.7%), 320 (5.4%) patients with heart failure (2.8%, n = 170), liver cirrhosis (0.7%, n = 40), or chronic kidney disease (1.9%, n = 113), diagnoses likely associated with the need for fluid restriction, were prescribed drugs for which abundant fluid at intake was recommended. Among 29 identified drugs, 15 drugs were administered to older patients over 75 years with fluid restriction due to said diseases.

Conclusions: Of patients 75 years and older with disease likely requiring water restriction, 5.4% faced the dilemma of following advice to restrict fluid intake due to their diagnoses or to adhere to instructions in drug package inserts to have abundant fluid intake when taking the drug. Our study raises awareness regarding the dilemma of water restriction and intake in clinical settings, highlighting the importance of considering individual patient needs. These real-world findings emphasize the need for information and guidelines to assist healthcare professionals in navigating this dilemma and making informed decisions for the benefit of their patients.

Background and objectives: There is a lack of well-controlled US studies of intramuscular (IM) interferon beta (IFNβ)-1a use in pregnant women with multiple sclerosis; however, in the European Medicines Agency region, IFNβ formulations may be considered during pregnancy if clinically needed based on data from European Union cohort registries. The AVONEX Pregnancy Exposure Registry was established to prospectively study the effects of IM IFNβ-1a on the risk of birth defects and spontaneous pregnancy loss in a US population.

Methods: Pregnant women with multiple sclerosis exposed to IM IFNβ-1a within ~ 1 week of conception or during the first trimester were included. Participants were followed until there was a pregnancy outcome, live-born infants were followed until age 8-12 weeks. Data were collected on IM IFNβ-1a exposure, demographics, patient characteristics, medical history, and pregnancy outcomes, including live births (with or without birth defect), spontaneous abortions/miscarriages and fetal death/stillbirth, elective abortions (with and without birth defect), and ectopic pregnancies. A population-based birth defect surveillance program, the Metropolitan Atlanta Congenital Defects Program (MACDP), served as the primary external control group for evaluating the risk of birth defects.

Results: Three-hundred and two patients with a median (range) age of 31.0 (16-48) years and a median (range) gestational age at the time of enrollment of 10.1 (4-39) weeks were evaluable. Most patients (n = 278/302; 92%) reported IM IFNβ-1a exposure in the week before conception and most (n = 293/302; 97%) discontinued treatment before the end of the first trimester. Of 306 pregnancy outcomes, there were 272 live births, 28 spontaneous abortions of 266 pregnancies enrolled before 22 weeks' gestation (rate 10.5%; 95% confidence interval 7.2-15.0), five elective abortions, and one stillbirth. There were 17 adjudicator-confirmed major birth defects of 272 live births (rate 6.3%; 95% confidence interval 3.8-10.0); the pattern of birth defects observed was not suggestive of a relationship to prenatal IM IFNβ-1a exposure.

Conclusions: This large US registry study suggests IM IFNβ-1a exposure during early pregnancy was not clinically associated with adverse pregnancy outcomes in women with multiple sclerosis. These findings help inform clinicians and patients in weighing the risks and benefits of IM IFNβ-1a use during pregnancy.

Clinical trial registration: ClinicalTrials.gov: NCT00168714, 15 September, 2005.

Background: Non-Hispanic Black and Hispanic persons with MS (pwMS) are more likely to experience rapid disease progression and severe disability than non-Hispanic White pwMS; however, it is unknown how the initiation of high-efficacy disease-modifying therapies (DMTs) differs by race/ethnicity. This real-world study describes DMT treatment patterns in newly diagnosed pwMS in the United States (US) overall and by race/ethnicity.

Methods: This retrospective analysis used the US Optum Market Clarity claims/electronic health records database (January 2015-September 2020). pwMS who were first diagnosed in 2016 or later and initiated any DMT in the two years following diagnosis were included. Continuous enrollment in the claims data for ≥ 12 months before and ≥ 24 months after diagnosis was required. Treatment patterns 2 years after diagnosis were analyzed descriptively overall and by race/ethnicity.

Results: The sample included 682 newly diagnosed and treated pwMS (non-Hispanic Black, n = 99; non-Hispanic White, n = 479; Hispanic, n = 35; other/unknown race/ethnicity, n = 69). The mean time from diagnosis to DMT initiation was 4.9 months in all pwMS. Glatiramer acetate and dimethyl fumarate were the most common first-line DMTs in non-Hispanic Black (28% and 20% respectively) and Hispanic pwMS (31%, 29%); however, glatiramer acetate and ocrelizumab were the most common in non-Hispanic White pwMS (33%, 18%). Use of first-line high-efficacy DMTs was limited across all race/ethnicity subgroups (11-29%), but uptake increased in non-Hispanic Black and White pwMS over the study period.

Conclusion: Use of high-efficacy DMTs was low across all race/ethnicity subgroups of newly diagnosed pwMS in the US, including populations at a greater risk of experiencing rapid disease progression and severe disability.

Background: Patients with inflammatory bowel diseases (IBDs) are at increased risk of pancreatitis. Data from a global safety database (GSD) were queried to identify risk factors for pancreatitis in vedolizumab-treated patients with IBD.

Methods: Takeda's GSD was retrospectively queried for case reports (CRs) of adverse events (AEs) following vedolizumab treatment, from licensure (May 20, 2014) through March 31, 2021. Unsolicited and solicited CRs of pancreatitis were coded using the Medical Dictionary for Regulatory Activities (MedDRA) High-Level Term "Acute and chronic pancreatitis." To examine factors associated with severe pancreatitis, serious CRs (serious AEs [SAEs]) were compared with SAEs from a comparator group of 600 random non-pancreatitis AEs. Comparisons were performed using t, χ², and Fisher's exact tests. Logistic regression was performed to adjust for covariates allowing backward selection.

Results: In total, 196 patients reported pancreatitis in > 700,000 patient-years of vedolizumab exposure. Pancreatitis was serious in 195 patients (99.5%), and non-pancreatitis AEs were serious in 195 of 600 (32.5%) in the random comparator group. In the pancreatitis group, 17 patients (8.7%) had a known history of pancreatitis versus none in the random comparator group. Younger age, vedolizumab indication of ulcerative colitis, concomitant medications (with a risk for pancreatitis), pancreatitis history, and comorbid conditions (especially ongoing pancreatitis) were associated with development of severe pancreatitis.

Conclusions: These analyses identified factors associated with pancreatitis SAEs in patients with IBD treated with vedolizumab, but do not suggest an increased risk of pancreatitis with vedolizumab. These findings will help inform which patients treated for IBD might have an elevated risk, regardless of treatment.