Meta-analysis and indirect treatment comparison of lipegfilgrastim with pegfilgrastim and filgrastim for the reduction of chemotherapy-induced neutropenia-related events.

Background Granulocyte colony-stimulating factors are effective at reducing the risk and duration of neutropenia. The current meta-analysis compared the neutropenia-related efficacy and safety of lipegfilgrastim to those of pegfilgrastim and filgrastim. Methods Embase was searched for trials examining the efficacy/safety of lipegfilgrastim, pegfilgrastim, or filgrastim. Outcomes included febrile neutropenia, severe neutropenia, duration of severe neutropenia, time to recovery of absolute neutrophil count, and incidence of bone pain. Direct comparisons were made using random-effects models. No trials directly compared lipegfilgrastim and filgrastim. Indirect comparisons were made between lipegfilgrastim and filgrastim with pegfilgrastim as the common comparator. Results This meta-analysis included a total of 5769 patients from 24 studies. Over all cycles, lipegfilgrastim showed a lower, nonsignificant risk of febrile neutropenia compared with pegfilgrastim. Lipegfilgrastim has a lower risk of febrile neutropenia versus filgrastim but was also not statistically significant. The risk ratio for severe neutropenia in cycle 1 was 0.80, a 20% reduction in favor of lipegfilgrastim. For cycles 2-4, the risk ratio was 0.53 (0.35, 0.79) for lipegfilgrastim versus pegfilgrastim. The risk of severe neutropenia in cycles 2-4 was also significantly lower for lipegfilgrastim (risk ratio 0.45, 0.27, 0.75, respectively). No significant differences were found for febrile neutropenia and severe neutropenia in cycle 1. However, in cycles 2-4, lipegfilgrastim was associated with significant and clinically meaningful reductions in risk of severe neutropenia versus either pegfilgrastim or filgrastim. Conclusions Compared with pegfilgrastim or filgrastim, lipegfilgrastim has a statistically significantly lower absolute neutrophil count recovery time; however, differences in duration of severe neutropenia and bone pain were nonsignificant.

Impact of seizure frequency reduction on health-related quality of life among clinical trial subjects with refractory partial-onset seizures: A pooled analysis of phase III clinical trials of eslicarbazepine acetate.

BACKGROUND: Subjects who received eslicarbazepine acetate (ESL) as adjunctive therapy experienced significantly greater seizure frequency reduction (SFR) than placebo in three phase III, randomized, double-blind trials. This analysis compared changes in health-related quality of life (HRQOL) between treatment responders and non-responders across the pooled, per-protocol population (N=842) using the validated Quality of Life in Epilepsy Inventory-31 (QOLIE-31). METHODS: QOLIE-31 scores were calculated for Total Score (TS) and seven subscales; higher scores indicate better HRQOL. Mean changes from baseline were calculated. Analysis of covariance examined least square mean (LSM) differences in final scores between responders (≥50% and ≥75% SFR) and non-responders. Clinical significance was based on established minimal clinically important differences (MCIDs). RESULTS: Mean changes were greater among responders for TS (5.2 versus 1.4 for ≥50% SFR; 7.5 versus 1.9 for ≥75% SFR) and all subscales. Additionally, the percentage of subjects with changes meeting or exceeding MCIDs was higher among responders for TS (48.4% versus 33.9% for ≥50% SFR; 56.9% versus 35.8% for ≥75% SFR) and all subscales. Responders had significantly higher final scores for TS (LSM difference=4.0 for ≥50% SFR; LSM difference=5.7 for ≥75% SFR) and all subscales except emotional well-being at ≥50% SFR. LSM differences exceeded MCIDs at ≥75% SFR for TS and five of seven subscales, and two subscales at ≥50% SFR. In a subgroup analysis with placebo removed, LSM differences were larger overall. SIGNIFICANCE: In clinical trials of adjunctive ESL, higher levels of SFR were associated with greater improvements in HRQOL.

Severity and burden of partial-onset seizures in a phase III trial of eslicarbazepine acetate.

OBJECTIVE: The objective of this study was to compare posttreatment seizure severity in a phase III clinical trial of eslicarbazepine acetate (ESL) as adjunctive treatment of refractory partial-onset seizures. METHODS: The Seizure Severity Questionnaire (SSQ) was administered at baseline and posttreatment. The SSQ total score (TS) and component scores (frequency and helpfulness of warning signs before seizures [BS]; severity and bothersomeness of ictal movement and altered consciousness during seizures [DS]; cognitive, emotional, and physical aspects of postictal recovery after seizures [AS]; and overall severity and bothersomeness [SB]) were calculated for the per-protocol population. Analysis of covariance, adjusted for baseline scores, estimated differences in posttreatment least square means between treatment arms. RESULTS: Out of 547 per-protocol patients, 441 had valid SSQ TS both at baseline and posttreatment. Mean posttreatment TS for ESL 1200 mg/day was significantly lower than that for placebo (2.68 vs 3.20, p<0.001), exceeding the minimal clinically important difference (MCID: 0.48). Mean DS, AS, and SB were also significantly lower with ESL 1200 mg/day; differences in AS and SB exceeded the MCIDs. The TS, DS, AS, and SB were lower for ESL 800 mg/day than for placebo; only SB was significant (p=0.013). For both ESL arms combined versus placebo, mean scores differed significantly for TS (p=0.006), DS (p=0.031), and SB (p=0.001). CONCLUSIONS: Therapeutic ESL doses led to clinically meaningful, dose-dependent reductions in seizure severity, as measured by SSQ scores. CLASSIFICATION OF EVIDENCE: This study presents Class I evidence that adjunctive ESL (800 and 1200 mg/day) led to clinically meaningful, dose-dependent seizure severity reductions, measured by the SSQ.

Form CMS-2728 data versus erythropoietin claims data: implications for quality of care studies.

Medical Evidence Report Form CMS-2728 data is frequently used to study US dialysis patients, but the validity of these data have been called into question. We compared predialysis erythropoietin use as recorded on Form CMS-2728 with claims data as part of an assessment of quality of care among hemodialysis patients. Medicare claims were linked to Form CMS-2728 data for 18,870 patients. Dialysis patients, 67 years old or older, who started dialysis from 1 June 2005 to 31 May 2007 were eligible. Logistic and multivariate regressions were used to compare the use of either Form CMS-2728 or the corresponding claims data to predict mortality and the probability of meeting target hemoglobin levels. The sensitivity, specificity, and kappa coefficient for the predialysis erythropoietin indicator were 58.0%, 78.4%, and 0.36, respectively. Patients with a predialysis erythropoietin claim were less likely to die compared with patients without a claim (odds ratio = 0.80 and 95% confidence interval = 0.74-0.87), but there was no relationship observed between predialysis care and death using only Form CMS-2728 predictors. At the facility level, a predialysis erythropoietin claim was associated with a 0.085 increase in the rate of meeting target hemoglobin levels compared with patients without a claim (p = 0.041), but no statistically significant relationship was observed when using the Form CMS-2728 indicators. The agreement between Form CMS-2728 and claims data is poor and discordant results are observed when comparing the use of these data sources to predict health outcomes. Facilities with higher agreement between the two data sources may provide greater quality of care.

A quality initiative. Reducing rates of hospitalizations by objectively monitoring volume removal.

Morbidity, hospitalizations, and costs for the treatment of individuals with end-stage renal disease are simply not improving at a rate that is acceptable to many physicians and dialysis providers in the United States. Various conferences and papers have suggested what processes need to become part of the dialysis prescription to accelerate change. Controlling cardiovascular disease is a part of that change, and controlling extra-cellular volume (ECV) is necessary to accomplish this. Three dialysis providers joined in a quality initiative to objectively assess the ultrafiltration process and measure "normalized" ECV, with the outcome objective to decrease ECV-related hospitalizations. The results show a decrease in ECV-related hospitalizations by 50%. The model of dialysis prescription needs to now change to Kt/V + objective ECV control.

Venous thromboembolism incidence and risk factors associated with immune checkpoint inhibitors among patients with advanced non-small cell lung cancer.

BACKGROUND: Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in patients with lung cancer. Systemic therapies, such as chemotherapy (chemo), are associated with increased risk of VTE. Immune checkpoint inhibitors (ICIs) are a new standard of care for the treatment of lung cancer, but their association with VTE is not fully understood. We evaluated the incidence of VTE and risk factors for patients with advanced non-small cell lung cancer (aNSCLC) treated with first-line ICI-based, chemo-based, or ICI+chemo regimens. METHODS: This retrospective cohort study used HealthCore Integrated Research Environment - Oncology data, an integrated database of administrative claims, coupled with clinical data from a cancer-care quality program. Patients with first-line treatment of stage IV non-small cell lung cancer from July 2014 to August 2020 were grouped based on three treatment types: ICI-based, chemo-based, or ICI+chemo. Patients with VTE before initiation of systemic treatment were excluded. Newly diagnosed VTE events were identified via inpatient and outpatient diagnosis codes. Cox proportional hazards models were used to investigate the factors associated with VTE risk. RESULTS: Among 2299 eligible patients (ICI-based, n=605; chemo-based, n=1092; ICI+chemo, n=602) with a median follow-up of 9.1 months, the VTE incidence rates (95% CI) per 100 person-years were 17.8 (95% CI 16.0 to 19.5) overall, 13.5 (95% CI 10.6 to 16.5) for ICI-based, 18.0 (95% CI 15.5 to 20.5) for chemo-based, and 22.4 (95% CI 20.2 to 24.5) for ICI+chemo. The 6-month cumulative incidence of VTE was 8.1% for ICI-based, 10.9% for chemo-based, and 12.8% for ICI+chemo. Pulmonary embolism was most common, accounting for 63% of the VTE events. After controlling for baseline patient characteristics, the risk of VTE was 26% lower for ICI-based regimens than for chemo-based regimens (HR 0.74, p=0.03). There was no meaningful difference in the risk between ICI+chemo and chemo-based regimens (HR 1.12, p=0.36). Previous radiation and severe obesity (body mass index ≥40) were associated with VTE. CONCLUSIONS: VTE incidence rate per 100 person-years was common across regimens in patients with aNSCLC, but numerically lower for patients receiving ICI-based regimens compared with those receiving chemo-based and ICI+chemo regimens. VTE is a common complication of lung cancer, and there is a continued need for awareness of VTE as a comorbidity in this population.

Safety outcomes in patients with rheumatoid arthritis treated with abatacept: results from a multinational surveillance study across seven European registries.

BACKGROUND: Patients with rheumatoid arthritis (RA) have an increased risk of infection and malignancy compared with the general population. Infection risk is increased further with the use of disease-modifying antirheumatic drugs (DMARDs), whereas evidence on whether the use of biologic DMARDs increases cancer risk remains equivocal. This single-arm, post-marketing study estimated the incidence of prespecified infection and malignancy outcomes in patients with RA treated with intravenous or subcutaneous abatacept. METHODS: Data were included from seven European RA quality registries: ATTRA (Anti-TNF Therapy in Rheumatoid Arthritis [Czech Republic]), DANBIO (Danish Rheumatologic Database), ROB-FIN (National Registry of Antirheumatic and Biological Treatment in Finland), ORA (Orencia and Rheumatoid Arthritis [France]), GISEA (Italian Group for the Study of Early Arthritis), BIOBADASER (Spanish Register of Adverse Events of Biological Therapies in Rheumatic Diseases), and the SCQM (Swiss Clinical Quality Management) system. Each registry is unique with respect to design, data collection, definition of the study cohort, reporting, and validation of outcomes. In general, registries defined the index date as the first day of abatacept treatment and reported data for infections requiring hospitalization and overall malignancies; data for other infection and malignancy outcomes were not available for every cohort. Abatacept exposure was measured in patient-years (p-y). Incidence rates (IRs) were calculated as the number of events per 1000 p-y of follow-up with 95% confidence intervals. RESULTS: Over 5000 patients with RA treated with abatacept were included. Most patients (78-85%) were female, and the mean age range was 52-58 years. Baseline characteristics were largely consistent across registries. Among patients treated with abatacept, IRs for infections requiring hospitalization across the registries ranged from 4 to 100 events per 1000 p-y, while IRs for overall malignancy ranged from 3 to 19 per 1000 p-y. CONCLUSIONS: Despite heterogeneity between registries in terms of design, data collection, and ascertainment of safety outcomes, as well as the possibility of under-reporting of adverse events in observational studies, the safety profile of abatacept reported here was largely consistent with previous findings in patients with RA treated with abatacept, with no new or increased risks of infection or malignancy.

Mortality of dialysis patients according to influenza and pneumococcal vaccination status.

BACKGROUND: Data from an immunocompromised subpopulation in which both vaccine recipients and nonrecipients have frequent opportunities for vaccination can help determine the associations between vaccination against seasonal influenza and pneumococcal disease and all-cause mortality. STUDY DESIGN: We surveyed dialysis centers and performed a retrospective analysis of health status at dialysis therapy initiation, vaccination for influenza and pneumococcal disease, laboratory results, and mortality associated with the 2005-2006 influenza season for patients in 3 End-Stage Renal Disease Networks across the United States. SETTING & PARTICIPANTS: Of 1,033 dialysis facilities considered, 903 centers with a total patient population of 54,734 reported vaccination data. Analysis was limited to 36,966 patients on dialysis treatment for at least 1 year as of December 31, 2005. PREDICTOR: Vaccination status. OUTCOMES: OR for all-cause mortality (vaccinated vs unvaccinated patients). RESULTS: The estimated adjusted OR for mortality was significantly less than 1.0 for patient who received either vaccination and was lower for patients who had received both vaccinations than for those who had received either. Survival analysis confirmed these findings. LIMITATIONS: Possible misclassification due to self-report of vaccination for some patients. Lack of vaccination date. CONCLUSIONS: Vaccination against influenza and pneumococcal disease is associated with improved survival in dialysis patients. The 2 vaccinations have independent effects on mortality.

A group-randomized evaluation of a quality improvement intervention to improve influenza vaccination rates in dialysis centers.

BACKGROUND: Patients with end-stage renal disease (ESRD) are at high risk of complications from influenza, but many dialysis centers report <50% influenza immunization coverage. STUDY DESIGN: A group-randomized evaluation of a multicomponent intervention to increase influenza vaccination rates in poorly performing dialysis centers in ESRD Networks 6, 11, and 15. SETTING & PARTICIPANTS: Facilities with the lowest immunization percentages in 2006-2007 were selected from each network and randomly assigned to a standard (n = 39) or intensive intervention (n = 38). INTERVENTION: Standard intervention included a feedback report with comparison to other centers in their network and educational materials for staff and patients. Intensive-intervention centers also received 3 educational seminars, assistance with and review of center-specific action plans, and monthly monitoring of vaccination plan and rates. OUTCOMES: Change in vaccination rate in following year. MEASUREMENTS: Dialysis center records of patient vaccination status. RESULTS: There was an 8.9% (P = 0.04) adjusted mean absolute difference in improvement between intensive- and standard-intervention centers. LIMITATIONS: Some vaccinations were self-reported by patients. The vaccination data form does not have an option for patient data unavailable, which may have caused patients without data to be coded as unvaccinated. CONCLUSIONS: Multicomponent interventions may serve as a successful strategy to increase influenza vaccination rates at poorly performing centers, with a benefit beyond that provided by usual oversight and support.

Hemodialysis treatment center early mortality rates for incident hemodialysis patients are associated with the quality of care prior to starting but not following onset of dialysis.

BACKGROUND: We examined the independent contribution of pre-ESRD (end-stage renal disease) care and care after starting hemodialysis (post-HD) with facility-specific mortality among incident patients. METHODS: We studied 6,217 incident patients treated at 311 dialysis facilities. A pre-ESRD care score was assessed as the sum of quality measures met on the Centers for Medicare and Medicaid Services Form 2728, including predialysis nephrology and dietary care, having a fistula, hemoglobin and serum albumin. A post-HD care score was evaluated by the sum of quality targets attained, including HD adequacy, anemia, serum albumin and hemoglobin measured on an annual quality survey. A fifth post-HD care measure was having obtained an influenza vaccination during the current year. RESULTS: Individual patient mortality was associated with both pre-ESRD (p < 0.001) and post-HD (p < 0.001) care scores. Linear regression models including both pre-ESRD and post-HD care scores showed that a 1-point increase in the pre-ESRD care score resulted in a 0.30 (95% CI: -0.47, -0.12) decreased facility standardized mortality ratio; no association for post-HD care score was noted (-0.11; 95% CI: -0.26, 0.04). CONCLUSION: Pre-ESRD and post-HD care are both strongly associated with individual patient mortality. In contrast, only pre-ESRD care is associated with facility mortality, suggesting that early mortality reflects differences in pre-ESRD care in the community.

The treatment of ulnar impaction syndrome: a systematic review of the literature.

Ulnar impaction syndrome is a common cause of ulnar-sided wrist pain that is thought to be a result of abutment between the ulna and the ulnar carpus. A systematic review of the literature was conducted to determine the effectiveness of different treatment options in managing ulnar impaction syndrome. PubMed, the Cochrane database, and secondary references were reviewed to identify all English-language articles with reported results on the treatment of ulnar impaction syndrome. A total of 16 articles met the criteria for review. Three procedures were identified as the most commonly used in treating this syndrome: ulnar shortening osteotomy, the wafer procedure, and the arthroscopic wafer procedure. Mean time to union and percentage nonunion for the osteotomy group was 10.3 weeks and 1.7%, respectively. The overall complication rate for patients in the ulnar shortening osteotomy group, the wafer procedure group, and the arthroscopic wafer group was 30%, 8.8%, and 21%, respectively. The authors were unable to determine a single best treatment option based on the available studies, mainly due to the variability in the reporting of subjective outcome measures. Ulnar shortening osteotomy was associated with a higher complication rate than other procedures.

Association of standing-order policies with vaccination rates in dialysis clinics: a US-based cross-sectional study.

BACKGROUND: Patients with end-stage renal disease are at increased risk of morbidity and mortality because of infection. Quality improvement efforts for this patient population include assessment of institutional policies and practices that may increase vaccination rates for influenza, hepatitis B, and pneumococcal disease. STUDY DESIGN: A survey of vaccination practices, beliefs, and attitudes was sent to all dialysis centers in End-Stage Renal Disease Networks 6, 11, and 15. SETTING & PARTICIPANTS: Of 1,052 dialysis facilities considered, 683 returned the survey, reported vaccination rates for 2005 to 2006, and had 20 or more patients. PREDICTOR OR FACTOR: Standing-order policy of the dialysis facility, categorized as facility-wide orders, preprinted admission orders for each patient (chart orders), physician-specific orders, and individual orders. OUTCOMES: Vaccination rates for influenza, hepatitis B (full or partial series), hepatitis B, and pneumococcal vaccine. MEASUREMENTS: Patient vaccination, given at or outside the center. RESULTS: Overall vaccination rates were 76% +/- 18% (SD) for influenza, 73% +/- 22% for hepatitis B full or partial series, 62% +/- 25% for hepatitis B full series, and 44% +/- 34% for pneumococcal vaccine. Compared with individual orders, facility-wide standing orders and chart orders were not associated with greater vaccination rates for influenza (0.4%; confidence interval, -4 to 5; and 1.27%; confidence interval, -3 to 5, respectively), but were associated with greater vaccination rates for hepatitis B full or partial series (9%; confidence interval, 3 to 15; and 11%; confidence interval, 5 to 17, respectively), hepatitis B full series (11%; confidence interval, 4 to 17; and 13%; confidence interval, 7 to 19, respectively), and pneumococcal disease (21%; confidence interval, 14 to 29; and 20%; confidence interval, 13 to 27, respectively). LIMITATIONS: Data are cross-sectional, and vaccinations outside the center were self-reported. CONCLUSIONS: Existing facility-wide or chart-based order programs may be effective in promoting vaccination against hepatitis B and pneumococcal disease.

Understanding factors that contribute to the disposal of unused opioid medication.

PURPOSE: Drivers of excess controlled substance disposal behaviors are not well understood. A survey of patients who had received opioid-based medications was conducted to inform the design of future innovative drug take-back programs. METHODS: This was a cross-sectional survey study conducted in 152 participants who received treatment with an opioid within the previous 2 years and had possession of unused medication following either switching to a different opioid or discontinuation of pain. RESULTS: Approximately one-third of patients had disposed of their unused opioid medication. Education about the importance of and appropriate methods for drug disposal was associated with a significantly increased likelihood of patients disposing of unused medication, and it was observed that patients prescribed an immediate-release/short-acting opioid were twice as likely to keep their medication compared to those prescribed an extended-release/long-acting opioid. The most commonly reported methods for disposal were via drug return kiosks and flushing the medication down the toilet. Some of the most impactful drivers of unused opioid disposal were routine practice of disposing of all unused drugs and instruction from a health care provider, and the most common driver of keeping unused medication was the desire to have it on-hand should there be a need to treat pain in the future. Over 80 % of patients indicated that they would be more likely to use a drug take-back service if they were offered compensation or if the kiosk was in a location that they visited frequently, and approximately half of the patients indicated that they would be willing to request an initial partial fill of an opioid prescription to reduce the volume of unused medication. CONCLUSION: There is a clear need to increase patient awareness about the importance and methods of proper medication disposal, and a great opportunity for health care providers to increase patient education efforts. These study findings also highlight key areas for improvement in drug take-back programs that may promote and incentivize more patients to utilize the services.

Real-world utilization of once-daily extended-release abuse deterrent formulation of hydrocodone: a comparison with the pre-approval randomized clinical trials.

BACKGROUND AND OBJECTIVE: Hydrocodone bitartrate extended release (Hysingla® ER, HYD) was previously studied in a 12-week randomized, double-blind, placebo-controlled trial and a 52-week open-label safety study. Both of these preapproval studies allowed dose titration to efficacy. The purpose of the present analysis was to compare dosing and utilization patterns in these previous clinical trials with real-world data (RWD) usage in a retrospective claim analysis performed 12-14 months post approval in the US. METHODS: In the claim analysis (Truven Health Analytics MarketScan® Research Database), patients prescribed HYD between January 1, 2015, and April 30, 2016, were followed for up to 6 months of continuous HYD use. Daily average consumption (DACON), initial dose, rescue opioid use and total milligram dose over time were also evaluated. RESULTS: HYD daily dose stabilized at ~60 mg dose once daily across all three studies. There was also a reduced need for rescue medication with HYD, resulting in a lower total opioid milligram dose over time. In the claim analysis, the mean monthly HYD dose increased from 49 to 55 mg in month 2 and then remained stable through month 6. The mean (standard deviation [SD]) time on drug was 79.5 days (61.42 days), and DACON was 1.04 pills/day, corresponding to the approved full prescribing information (FPI) and once-daily dosing. CONCLUSION: In 12-14 months post approval, real-world dosing and utilization of HYD mirrored registration and open-label study findings, with stable once-daily dosing of ~60 mg and no increase in rescue medicine utilization.

Medical resource utilization in dermatomyositis/polymyositis patients treated with repository corticotropin injection, intravenous immunoglobulin, and/or rituximab.

BACKGROUND: Dermatomyositis and polymyositis (DM/PM) are rare, incurable inflammatory diseases that cause progressive muscle weakness and can be associated with increased medical resource use (MRU). When corticosteroid treatment is unsuccessful, patients may receive intravenous immunoglobulin (IVIg), rituximab, or repository corticotropin injection (RCI). This study compared real-world, non-medication MRU between patients treated with RCI and those treated with IVIg and/or rituximab for DM/PM. METHODS: Claims of DM/PM patients were analyzed from the combination of three commercial health insurance databases in the United States from July 2009 to June 2014. Patients treated with RCI were propensity score matched to those treated with IVIg, rituximab, and both (IVIg+rituximab) based on demographics, prior clinical characteristics, and prior MRU. Per-patient per-month (PPPM) MRU and costs were compared using Poisson regression and generalized linear modeling, respectively. RESULTS: One-hundred thirty-two RCI, 1,150 IVIg, and 562 rituximab patients had an average age of 52.6, 46.6, and 51.7 years, respectively, and roughly two-thirds were female. After matching, there were no significant differences in demographics or prior clinical characteristics. RCI patients had fewer PPPM hospitalizations (0.09 vs 0.17; P=0.049), shorter length of stay (LOS; 3.24 days vs 4.55 days; P=0.004), PPPM hospital outpatient department (HOPD) visits (0.60 vs 1.39; P<0.001), and PPPM physician office visits (2.01 vs 2.33; P=0.035) than IVIg. RCI had fewer PPPM HOPD visits (0.56 vs 0.92; P<0.001) than rituximab. Patients treated with RCI had shorter LOS (2.18 days vs 5.15; P<0.001) and less PPPM HOPD visits (0.53 vs 1.26; P<0.001) than IVIg+rituximab. Total non-medication PPPM costs were 23%-75% lower for RCI compared to IVIg ($2,126 vs $3,964; P<0.001), rituximab ($2,008 vs $2,607; P=0.018), and IVIg+rituximab ($1,234 vs $4,858; P<0.001). CONCLUSION: Patients treated with RCI had less PPPM non-medication MRU and costs than those treated with IVIg and/or rituximab, particularly in the hospital setting where significant costs are incurred.

Mortality rates do not differ among patients prescribed various vitamin D agents.

BACKGROUND: Limited well-controlled research exists examining the impact of different formulations of oral vitamin D on clinical outcomes in dialysis patients, specifically those on peritoneal dialysis. For this retrospective mortality analysis, we compared mortality rates of patients on 3 of the most commonly prescribed vitamin D agents. METHODS: We examined 2 years (7/1/2008 to 6/30/2010) of oral medication records of peritoneal dialysis patients from a large US dialysis organization. Patients were identified whose physicians prescribed a single form of vitamin D (calcitriol, paricalcitol, or doxercalciferol) for ≥ 90% of all patient-months. We excluded incident patients (< 90 days on dialysis) and patients whose physicians treated < 5 peritoneal dialysis patients at a dialysis facility, and we assessed mortality. RESULTS: The analysis inclusion criteria identified 1,707 patients. The subset in this analysis included 12.6% of all prevalent peritoneal dialysis patients and 11.8% of prevalent patient-months. Patients with physicians who predominately prescribed calcitriol had a lower mortality rate: 9.33 (confidence interval (CI) 7.06, 11.60) deaths per 100 patient-years than the doxercalciferol, 12.20 (CI 9.34, 15.06) or paricalcitol, 12.27 (CI 9.27, 15.28) groups. However, these differences were not statistically significant. A Cox proportional hazards model, adjusting for differences in age, vintage, gender, race, body mass index, and comorbidities also showed no significant differences. CONCLUSIONS: For this peritoneal dialysis population, instrumental variable analyses showed no significant difference in mortality in patients taking the most common oral vitamin D formulations (calcitriol, doxercalciferol, paricalcitol).

Ferric Citrate, an Iron-Based Phosphate Binder, Reduces Health Care Costs in Patients on Dialysis Based on Randomized Clinical Trial Data.

BACKGROUND: Patients with end-stage renal disease (ESRD) require phosphate binders for hyperphosphatemia and erythropoiesis-stimulating agents (ESAs) and intravenous (i.v.) iron for anemia. Ferric citrate (FC) is a novel, iron-based phosphate binder that increases iron stores and decreases i.v. iron and ESA usage while maintaining hemoglobin levels, and may decrease the cost of ESRD care. The study objectives were to (1) quantify differences in ESA and i.v. iron usage among ESRD patients receiving FC compared with active control (AC) (sevelamer carbonate and/or calcium acetate) on the basis of data from a 52-week phase III clinical trial and (2) standardize trial data to the general United States (US) ESRD population and calculate the potential impact of FC on ESRD cost/patient/year in the USA. STUDY DESIGN: The study was a randomized, controlled clinical trial. SETTING AND POPULATION: A total of 441 adult subjects with ESRD who received FC or AC for 52 weeks were included. MODEL, PERSPECTIVE, AND TIMELINE: Differences in ESA and i.v. iron usage between the treatment groups were modeled over time using generalized linear mixed models and zero-inflated Poisson models. Trends were modeled via logarithmic curves, and utilization patterns were applied to the general dialysis population to estimate expected resource savings. OUTCOMES: Study outcomes were costs saved/patient/year using FC versus AC (US dollars). RESULTS: Our model suggests an annual decrease of 129,106 U of ESAs and 1960 mg of i.v. iron per patient in the second year after a switch from AC to FC. Applying 2013 Medicare pricing, this would save $1585 in ESAs and $516 in i.v. iron: a total of $2101/patient/year; these savings would be expected to double for managed care plans. LIMITATIONS: The projections were made on 1 year of trial data. CONCLUSIONS: Phosphate binding with FC reduces i.v. iron and ESA usage. Given the high cost burden of ESRD, our model demonstrates significant potential cost savings. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01191255) http://clinicaltrials.gov/ct2/show/NCT01191255 .

Reduced use of erythropoiesis-stimulating agents and intravenous iron with ferric citrate: a managed care cost-offset model.

BACKGROUND: Ferric citrate (FC) is a phosphate binder in development for the treatment of hyperphosphatemia in patients with end-stage renal disease (ESRD). In clinical trials, FC improved patient serum phosphorus levels and increased serum ferritin and percent transferrin saturation. Because nephrologists respond to increases in these iron measures by reducing intravenous (IV) iron and erythropoiesis-stimulating agent (ESA) doses, the decreased use of iron and ESA associated with FC may reduce costs. OBJECTIVES: To develop a cost-offset model from a managed care perspective estimating the cost savings associated with FC use. METHODS: We created a cost-offset model from the managed care payer perspective that compared the treatment costs of ESRD for patients given FC. The model considered the number of dialysis sessions per month; number of ESRD patients enrolled in the health plan; cost of ESAs, iron, and dialysis sessions; and the proportion of patients on phosphate binder therapy. The model assumed equivalent efficacy and cost neutrality between FC and other phosphate binders. Monte Carlo simulations were conducted by varying model inputs. RESULTS: When FC was compared to other phosphate binders, the monthly cost of ESA and IV iron per 500 patients with ESRD (85% treated with phosphate binders) was reduced by 8.15% and 33.2%, respectively. When incorporated into the total cost of dialysis for patients with ESRD (dialysis, ESA, and IV iron), the decrease in the monthly cost of dialysis care was US$80,214 per 500 ESRD patients. Monte Carlo simulations suggest that a plan serving 500 dialysis patients could save between US$626,000 and US$1,106,000 annually with the use of FC. CONCLUSION: The use of FC in ESRD patients with hyperphosphatemia may help reduce treatment costs.