Effects of deferasirox-deferoxamine on myocardial and liver iron in patients with severe transfusional iron overload.

Deferasirox (DFX) monotherapy is effective for reducing myocardial and liver iron concentrations (LIC), although some patients may require intensive chelation for a limited duration. HYPERION, an open-label single-arm prospective phase 2 study, evaluated combination DFX-deferoxamine (DFO) in patients with severe transfusional myocardial siderosis (myocardial [m] T2* 5-<10 ms; left ventricular ejection fraction [LVEF] ≥56%) followed by optional switch to DFX monotherapy when achieving mT2* >10 ms. Mean dose was 30.5 mg/kg per day DFX and 36.3 mg/kg per day DFO on a 5-day regimen. Geometric mean mT2* ratios (Gmeanmonth12/24/Gmeanbaseline) were 1.09 and 1.30, respectively, increasing from 7.2 ms at baseline (n = 60) to 7.7 ms at 12 (n = 52) and 9.5 ms at 24 months (n = 36). Patients (17 of 60; 28.3%) achieved mT2* ≥10 ms and ≥10% increase from baseline at month 24; 15 switched to monotherapy during the study based on favorable mT2*. LIC decreased substantially from a baseline of 33.4 to 12.8 mg Fe/g dry weight at month 24 (-52%). LVEF remained stable with no new arrhythmias/cardiac failure. Five patients discontinued with mT2* <5 ms and 1 died (suspected central nervous system infection). Safety was consistent with established monotherapies. Results show clinically meaningful improvements in mT2* in about one-third of patients remaining on treatment at month 24, alongside rapid decreases in LIC in this heavily iron-overloaded, difficult-to-treat population. Combination therapy may be useful when rapid LIC reduction is required, regardless of myocardial iron overload. This trial was registered at www.clinicaltrials.gov as #NCT01254227.

Research Protocol for an Observational Health Data Analysis on the Adverse Events of Systemic Treatment in Patients with Metastatic Hormone-sensitive Prostate Cancer: Big Data Analytics Using the PIONEER Platform.

Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report drug-related adverse events (AEs), which are correlated with systemic combination therapies for mHSPC. Determining the optimal treatment option requires large cohorts to estimate the tolerability and AEs of these combination therapies in "real-life" patients with mHSPC, as provided in this study. We use a network of databases that includes population-based registries, electronic health records, and insurance claims, containing the overall target population and subgroups of patients defined by unique certain characteristics, demographics, and comorbidities, to compute the incidence of common AEs associated with systemic therapies in the setting of mHSPC. These data sources are standardised using the Observational Medical Outcomes Partnership Common Data Model. We perform the descriptive statistics as well as calculate the AE incidence rate separately for each treatment group, stratified by age groups and index year. The time until the first event is estimated using the Kaplan-Meier method within each age group. In the case of episodic events, the anticipated mean cumulative counts of events are calculated. Our study will allow clinicians to tailor optimal therapies for mHSPC patients, and they will serve as a basis for comparative method studies.

Real-world patient characteristics associated with survival of 2 years or more after radium-223 treatment for metastatic castration-resistant prostate cancer (EPIX study).

BACKGROUND: The real-world EPIX study was conducted to gather information about the characteristics of patients with metastatic castration-resistant prostate cancer (mCRPC) who survived ≥2 years after treatment with the alpha-emitter radium-223. METHODS: This retrospective study of electronic health records in the US Flatiron database (NCT04516161) included patients with mCRPC treated with radium-223 between January 2013 and June 2019. Median overall survival (OS) and prostate-specific antigen (PSA) response (≥50% reduction) from start of radium-223 treatment were the primary and secondary endpoints, respectively. Patient characteristics were compared between those who survived ≥2 years versus <2 years, including a subgroup who survived <6 months. RESULTS: In the 1180 patients identified, median OS was 12.9 months (95% CI: 12.1-13.7), and 13% of patients with data at 6 months had a PSA response. The survival groups included 775 patients (65.7%) who survived <2 years (including 264 (22.4%) who survived <6 months) and 185 patients (15.7%) who survived ≥2 years; 220 patients (18.6%) had incomplete follow-up data and were censored. On multivariate analysis, age >75 years, Eastern Cooperative Oncology Group performance status (ECOG PS) 2-4, visceral metastases, prior symptomatic skeletal events (SSEs), and prior chemotherapy were independently prognostic of reduced OS. For patients with survival ≥2 years versus <2 years, median age was 71 versus 75 years, 4% versus 14% had ECOG PS 2-4, 4% versus 10% had visceral metastases, 38% versus 44% had prior SSEs, and 16% versus 32% had prior chemotherapy. CONCLUSIONS: In this study of men with mCRPC treated in real-world clinical practice, median OS was consistent with that seen in the phase 3 ALSYMPCA trial. Patients who survived ≥2 years after the start of radium-223 were younger and had better ECOG PS, lower disease burden, and less use of prior chemotherapy than those who survived <2 years.

Treatment Patterns in Patients with Incident Parkinson's Disease in the United States.

BACKGROUND: Treatment patterns in Parkinson's disease (PD) have not been extensively studied for nearly two decades. Insurance claims are appropriate for such analysis. OBJECTIVE: To understand the standard of care use of symptomatic treatments in new cases of PD and factors associated with treatment choice. METHODS: Retrospective cohort study using claims data from the United States between 2008 and 2016. We used Kaplan-Meier methodology to estimate time to treatment start and switch or add-on therapy and Cox proportional hazards models to identify predictors. RESULTS: We identified 68,532 patients eligible for treatment pattern analyses. Median time from diagnosis until first treatment was 37 days (95% confidence interval: 36-38). Two distinct patterns of treatment initiation were identified: fast initiators and patients with delayed treatment start (or no recorded treatment). Levodopa therapies were the most commonly prescribed treatment class (52.6%). Increased age was associated with shorter time to start of treatment with levodopa. Younger age was associated with shorter time to initiation of dopamine agonists and other symptomatic treatments. Patients that initiated treatment with levodopa/combinations had the fewest switches/add-ons [30.4%; median time 7.29 (6.71, 8.13) years]. Older patients had fewer switch/add-on therapies, but only in the group that started with levodopa/combination therapy. CONCLUSIONS: Time from diagnosis to treatment start was relatively short, suggesting that PD diagnosis, as reflected in the database, is closely linked to start of symptomatic treatment. Levodopa treatment remains the most common treatment, especially for older patients. Delayed treatment start was associated with increased age and comorbidity.

Once-every-2-weeks and once-weekly epoetin beta regimens: equivalency in hemodialyzed patients.

BACKGROUND: Currently, less frequent than once-weekly subcutaneous epoetin administration regimens were shown to be equally effective and safe as once-weekly schedules in stable predialysis and peritoneal dialysis patients. Bioequivalency of once-every-2-weeks and once-weekly subcutaneous administration of the same total dose of epoetin beta for the maintenance phase of anemia treatment in stable iron-replete long-term hemodialysis patients therefore was investigated prospectively. METHODS: Two hundred seven stable selected hemodialysis patients without diabetes, acute illness, significant inflammation, malnutrition or hyperparathyroidism administered once-weekly subcutaneous epoetin beta and preserving stable hemoglobin levels between 10 and 12 g/dL (100 and 120 g/L; difference between maximum and minimum of 3 subsequent levels

Clinical outcomes and quality of life in elderly patients on peritoneal dialysis versus hemodialysis.

OBJECTIVE: To compare clinical outcomes and quality of life (QOL) in elderly patients on peritoneal dialysis (PD) and hemodialysis (HD) in the North Thames Dialysis Study. DESIGN: A 12-month prospective cohort study. SETTING: Four hospital-based renal units in London, UK. PATIENTS: 174 patients that were 70 years or older at the start of dialysis, separated into two cohorts: 78 new patients (36 PD, 42 HD) that were recruited after 90 days of chronic dialysis; and 96 stock patients (42 PD, 54 HD) that were already on dialysis during the recruitment period. MAIN OUTCOME MEASURES: 12-month survival and hospitalization rate, and QOL assessed at baseline and at 6 and 12 months by the SF-36 and the Symptoms/Problems scale of the Kidney Disease Quality of Life Questionnaire (KDQOL). RESULTS: Peritoneal dialysis and HD patients were similar for sociodemographic and clinical characteristics. Annual mortality and hospitalization rates in PD versus HD patients were 26.1 versus 26.4 deaths/100 person-years and 1.9 versus 2.0 admissions/person-year, respectively. Adjusted relative risks showed no effect of modality on clinical outcomes. Multiple linear regression analyses of QOL at baseline showed similar SF-36 scores between PD and HD patients, but higher KDQOL scores in PD patients (3.5 points higher, 95% confidence interval 0.3-6.6). There was, however, no effect of dialysis modality on QOL at 6 or 12 months. CONCLUSIONS: Clinical outcomes and QOL are similar in elderly people on PD and HD. Peritoneal dialysis is a viable option for more than a carefully selected minority of elderly people requiring dialysis.

Costs of dialysis for elderly people in the UK.

BACKGROUND: Growing acceptance rates of elderly patients for dialysis requires a careful planning of renal services expansion. As little is known about the actual resource use in patients 70 years and over, we evaluated the entire range of costs related to treatment, hospitalization, medication and other health and social service use, and assessed the impact of socio-demographic and clinical factors on costs. METHODS: Service use and costs were assessed in a 12-month prospective cohort study of 171 dialysis patients, 70 years of age and over, from four hospital-based renal units in London, UK. RESULTS: Total costs ranged between 14,940 pounds and 58,250 pounds per annum. The average annual cost was 22,740 pounds [95% confidence interval (CI), 21,470-24,020 pounds]. The majority of costs were allocated to dialysis treatment and transport (70%), hospitalizations (12%) and medication (12%). Other health and social services accounted for only 6% of total costs. Dialysis and hospitalization costs were pound 68.4 per day on average. Univariate subgroup analyses showed no significant difference between patients on peritoneal dialysis (64.5 pounds) and haemodialysis (71.5 pounds, P = 0.13). Age 80 years and over and presence of peripheral vascular disease (PVD) were associated with higher daily costs of 73.3 pounds compared with 63.2 pounds in the 70-74 age group (P = 0.033) and 76.9 pounds vs 63.8 pounds in patients without PVD (P = 0.022), respectively. Proximity to death was associated with a nearly pound 40 increase in daily costs (96.8 vs 59.7 pounds; P < 0.001). Multiple linear regression analyses confirmed these findings and showed that age 80 years and over and presence of peripheral and cerebrovascular disease were significant predictors of costs. There was a large but marginally significant difference in costs in patients with cancer. We found no evidence that diabetes was associated with higher dialysis and hospitalization costs. CONCLUSIONS: The costs of providing dialysis for patients 70 years and over are largely shaped by the treatment costs rather than by use of community health and social services. Though age above 80 and co-morbidity are associated with increased resource use, average treatment costs are not higher than estimates for dialysis patients in general. This suggests that there is no case for providing treatment to younger patients and denying it to elderly patients on grounds of cost.