Effectiveness and safety in non-valvular atrial fibrillation patients switching from warfarin to direct oral anticoagulants in US healthcare claims.

INTRODUCTION: There is a paucity of real-world studies examining the risks of stroke/systemic embolism (SE) and major bleeding (MB) among non-valvular atrial fibrillation (NVAF) patients switching from warfarin to a direct oral anticoagulant (DOAC). This retrospective study was conducted to compare the stroke/SE and MB risks between patients switched from warfarin to apixaban, dabigatran, or rivaroxaban in real-world clinical practice. MATERIALS AND METHODS: This study used data from four United States commercial claims databases from January 1, 2012 to June 30, 2019. The study population included NVAF patients initially treated with warfarin and switched to apixaban, dabigatran, or rivaroxaban within 90 days of their warfarin prescription ending. Patients were matched 1:1 between the DOACs in each database using propensity scores and then pooled for the final analysis. Cox proportional hazards models were used to calculate the risk of stroke/SE and MB. RESULTS AND CONCLUSIONS: The final population consisted of 2,611 apixaban-dabigatran, 12,165 apixaban-rivaroxaban, and 2,672 dabigatran-rivaroxaban pairs. Apixaban vs. dabigatran was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.39-0.96) and MB (HR: 0.67; 95% CI: 0.50-0.91). Apixaban vs. rivaroxaban was associated with a similar risk of stroke/SE (HR: 0.88; 95% CI: 0.73-1.07) and a lower risk of MB (HR: 0.60; 95% CI: 0.52-0.68). There was no significant difference in either risk between dabigatran and rivaroxaban. These results provide important insights into how the risks of stroke/SE and MB for NVAF patients vary when switching from warfarin to different DOACs.

Effectiveness and safety of anticoagulants among patients with venous thromboembolism and active cancer who also had prior bleed or prior renal disease.

OBJECTIVE: Patients with active cancer and venous thromboembolism (VTE) have elevated risk of recurrent VTE (rVTE) and major bleeding (MB). The risk is even higher within those with a prior bleeding event or renal disease. There is a need to understand the risk of rVTE and MB of commonly used anticoagulants among these high-risk patients. METHODS: VTE patients with active cancer and treated with apixaban, warfarin, or low molecular weight heparin (LMWH) within 30 days of VTE were identified from five claims databases in the United States. Inverse probability of treatment weighting (IPTW) was used to balance patient characteristics. The post-IPTW population was stratified by prior bleed or renal disease status. Cox proportional hazards models were used to evaluate interactions between treatment and prior bleed or renal disease on risk of rVTE and MB, with p value <.1 considered significant. RESULTS: Study criteria were met by 30,586 VTE cancer patients: 35.0% had prior bleed and 29.0% had renal disease. For apixaban, LMWH, and warfarin cohorts, the incidence (events per 100 person-years) of MB was higher in patients with prior bleed (17.48 vs 7.58, 25.61 vs 13.11, and 20.38 vs 8.97) or renal disease (15.79 vs 8.71, 22.11 vs 15.90, and 18.49 vs 10.39) vs those without the conditions. Generally, there were no significant interactions between anticoagulant use and prior bleed or renal disease on rVTE and MB (p for interaction >.1). CONCLUSION: The incidence of MB was higher among those with prior bleed or renal disease. Effects of apixaban, warfarin, or LMWH were generally consistent regardless of prior bleed or renal disease status.

Effectiveness and safety of anticoagulants among patients with venous thromboembolism and common cancers or cancers with high venous thromboembolism risk.

Aim: Treatment effects among anticoagulant-treated patients with venous thromboembolism (VTE) and cancer across tumor types were evaluated. Methods: Patients initiating an anticoagulant within 30 days after VTE were identified. After inverse probability treatment weighting, patients were stratified by tumor type. Interactions between treatment and tumor type on recurrent VTE, major bleeding and clinically relevant non-major bleeding were assessed using Cox proportional hazard models. Results: Treatment effects were generally not significantly different among patients with or without the following cancer types: prostate, breast, lung, pancreatic or multiple myeloma. Few significant interactions were observed for lung and pancreatic cancer. Conclusion: Anticoagulant treatment effects were generally consistent across tumor types. The significant interactions may indicate tumor-specific effects of anticoagulants, but further research is needed.

Effectiveness and safety of anticoagulants among venous thromboembolism cancer patients with and without brain cancer.

INTRODUCTION: Patients with brain cancer are at a high risk of developing venous thromboembolism (VTE) and are underrepresented in clinical trials. This study compared the risk of recurrent VTE (rVTE), major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) among VTE cancer patients initiating apixaban, low molecular weight heparin (LMWH), or warfarin stratified by patients with brain vs other cancer types. MATERIALS AND METHODS: Active cancer patients initiating apixaban, LMWH, or warfarin within 30 days after VTE diagnosis were identified from 4 US commercial and the Medicare databases. Inverse probability of treatment weights (IPTW) was used to balance patient characteristics. Cox proportional hazards models were used to evaluate the interaction between brain cancer status and treatment on outcomes (rVTE, MB, and CRNMB), with a p-value <0.1 indicating a significant interaction. RESULTS: Of 30,586 patients with active cancer (5 % had brain cancer), apixaban (vs. LMWH and warfarin) was associated with lower risk of rVTE, MB, and CRNMB. Generally, no significant interactions (P > 0.1) were found between brain cancer status and anticoagulant treatment across outcomes. The exception was MB for apixaban [vs LMWH (p-value for interaction = 0.091)] with a higher reduction among those with brain cancer (HR = 0.32) than those with (HR = 0.72) other cancer. CONCLUSIONS: Among VTE patients with all types of cancer, apixaban (vs LMWH and warfarin) was associated with a lower risk of rVTE, MB, and CRNMB. In general, anticoagulant treatment effects were not significantly different between VTE patients with brain cancer and those with other cancer.

Trends and factors associated with outpatient anticoagulant treatment initiation among VTE patients with active cancer.

BACKGROUND: Patients with venous thromboembolism (VTE) and cancer are at higher risk of recurrent VTE and mortality. Clinical guidelines recommend anticoagulant treatment for these patients. This study assessed trends in outpatient anticoagulant treatment and factors associated with this treatment initiation in outpatient setting among this high-risk patient population. OBJECTIVE: To study trends and factors associated with anticoagulant treatment initiation among patients with VTE and cancer. METHODS: VTE cancer patients age ≥65 were identified from the SEER-Medicare database from 01JAN2014-31DEC2019. Patients were enrolled for ≥6 months prior to their first VTE (i.e. index event) and without evidence of other reasons for anticoagulation (i.e., atrial fibrillation). Patients were also required to be enrolled for ≥30 days after index. Cancer status was identified from SEER or Medicare database in the 6 months pre- through 30 days post-VTE. Patients were classified into treated or untreated cohorts depending on whether they initiated outpatient anticoagulant treatment within 30 days post-index. The trends of treated vs. untreated were evaluated by quarter. Logistic regression was used to identify demographic-, VTE-, cancer- and comorbid-related factors associated with anticoagulant treatment initiation. RESULTS: A total of 28,468 VTE-cancer patients met all study criteria. Of these, ~46 % initiated outpatient anticoagulant treatment within 30 days, and ~54 % did not. The above rates were stable from 2014 to 2019. Factors such as VTE diagnosis in inpatient setting, pulmonary embolism (PE) diagnosis, and pancreatic cancer were associated with increased odds whereas bleeding history and some comorbid factors were associated with decreased odds of initiating anticoagulant treatment. CONCLUSION: Over half of VTE patients with cancer did not initiate outpatient anticoagulant treatment within the first 30-days after VTE diagnosis. This trend was stable from 2014 to 2019. A range of cancer-, VTE-, and comorbid-related factors were associated with the likelihood of the treatment initiation.

Development of a claims-based flare algorithm for systemic lupus erythematosus.

OBJECTIVE: To develop a claims-based algorithm identifying systemic lupus erythematosus (SLE) flares using a linked claims-electronic medical record (EMR) dataset. METHODS: This study was a retrospective analysis of linked administrative claims and EMR data spanning 1 January 2003 to 31 March 2019. Included were adult SLE patients with at least 12 months of continuous enrollment in claims data, 12 months of clinical activity in EMR, and an absence of malignancies excluding basal and squamous cell carcinoma. Patient follow-up was divided into 30-day windows, and a proxy SLEDAI-2K score based on the EMR data was calculated for each 30-day period. A flare was defined as an increase of at least 4 from the baseline score. A series of potential flare predictor variables identified in claims were based on a combination of established variables from a previous algorithm, with the addition of other SLE-related indicators based on clinical input. Logistic regression models were built to predict monthly SLE flares. RESULTS: Inclusion criteria identified 2427 patients. Results from a logistic model with forward selection capping the number of variables at 10 performed well with a c-statistic of 0.76 and a Brier score of 0.07. The top five predictors were any inpatient admission (OR = 4.76), outpatient office visit (OR = 3.04), MRI (OR = 2.26), ER visit (OR = 2.25), and number of rheumatology visits (OR = 1.75); p < .01 for all. CONCLUSIONS: The final algorithm shows promise in providing an alternative and more streamlined way for identifying likely flares in administrative claims data that will advance the study of SLE within the context of flares.

Treatment Patterns and Relapses Among Newly Treated Multiple Sclerosis Patients From a Retrospective Claims Analysis.

PURPOSE: Although all disease-modifying therapies (DMTs) reduce risk of relapse in multiple sclerosis (MS), many factors, including route of administration, influence selection of first-line DMT. Knowledge of real-world treatment patterns and effectiveness in reducing relapses across DMTs is important to understanding factors influencing this choice. This study sought to describe treatment patterns and relapses among newly treated adults with MS and by DMT route of administration (oral, injectable, and infusion). METHODS: IBM MarketScan research databases were used to identify MS adults newly initiating DMTs (index event) from January 1, 2011-April 1, 2016, who had 12 months of continuous preindex and postindex medical and pharmacy benefits. Newly treated patients were those with ≥2 nondiagnostic claims with an International Classification of Diseases, Ninth Revision, Clinical Modification (340) or Tenth Revision, Clinical Modification (G35) code and no DMT prescription claims in the 12 months' preindex. Persistence and adherence were measured from index until the earliest of ≥60 days without DMT, switching DMTs, or end of follow-up. Relapses were defined using a validated claims-based algorithm and measured in the 12-month preindex and postindex periods. Regression analysis adjusting for patient characteristics and prior relapses was used to determine the association between DMT route of administration and odds of 12-month persistence, odds of postindex relapse, and number of postindex relapses. FINDINGS: Of 9378 newly treated MS patients meeting inclusion criteria; average age was 46.7 years, and 73.3% were female. Most patients initiated an injectable (65.5%) or oral (26.1%) DMT. Relapses decreased markedly from preindex to postindex (32.9%-24.0%), which was highest among oral users (35.8%-21.6%). Patients with no (vs ≥3) relapses preindex were more likely to be relapse free postindex (81.6% vs 31.4%). Nonpersistence (39.1% overall) was lowest among oral users (33.4%) and higher among those with versus without a postindex relapse (50.6% vs 35.5%). Patients initiating oral versus injectable agents were more likely to be persistent at 12 months (odds ratio [OR], 1.45; p < 0.0001) and less likely to relapse (OR, 0.75; p < 0.0001) postindex. Switches were uncommon (~10%) across cohorts. Preindex relapses were associated with increased odds of postindex relapses (OR, 1.73; p < 0.0001) but not with odds of persistence at 12 months. IMPLICATIONS: The 12-month nonpersistence rate was high among all MS patients but lower among oral users. Oral users were also less likely to relapse postindex. Despite the effectiveness of DMTs in reducing relapses, the low persistence, lack of switching to a new DMT, and continued relapses highlight an unmet need in the MS treatment landscape.

The economic burden of metastatic pancreatic cancer.

BACKGROUND: Objectives: Pancreatic cancer (PC) is a costly disease with a limited life-expectancy as it generally presents as an advanced, metastatic disease. Though current literature suggests cost varies by first line treatment, there is limited real-world knowledge about the economic burden of pancreatic cancer. This study describes the economic burden of pancreatic cancer patients overall and by observed first line treatments. METHODS: The IBM MarketScan databases were used to identify adult metastatic PC patients from January 1, 2010 through 3/31/2017. Those without other primary cancers, pregnancy, or prior PC treatment, and with 6 months of continuous enrollment prior to PC were included. Treatment patterns and healthcare utilization and expenditures were measured during the variable-length follow-up period. Continuous measures were presented as per patient per month (PPPM). RESULTS: A total of 6,360 patients met all inclusion criteria. Almost half (46.8%) of patients were untreated. Gemcitabine alone (15.6%) and FOLFIRINOX (11.4%) were the most commonly observed first line regimens. Treated patients incurred $17,513 PPPM (Gemcitabine alone) to $27,889 PPPM (FOLFIRINOX) during follow-up. Untreated patients incurred the highest unadjusted ($30,777 PPPM) and adjusted ($20,392 PPPM) cost. CONCLUSIONS: Metastatic PC patients incur a high economic burden driven by high utilization of healthcare resources, which varies by first line treatment. Also, the high proportion of untreated patients is alarming as these patients may be the most expensive of all patients. There is an unmet need in these patients for effective treatments that also reduce their economic burden.

Treatment patterns and direct medical costs among patients with advanced hepatocellular carcinoma.

AIMS: This study assessed the real-world United States (US) treatment patterns and the associated economic burden in patients diagnosed with advanced hepatocellular carcinoma (HCC). METHODS: The MarketScan database was used to identify patients newly diagnosed with HCC who received systemic therapy between 2011 and 2018 and continuously enrolled for ≥6 months (baseline period) prior and ≥1 month following HCC diagnosis. Treatment patterns (systemic and locoregional therapy), healthcare resource utilization, and costs were reported during follow-up. RESULTS: The final sample included 1580 patients (median age, 61; 78% male; median follow up, 8.7 months). The most common first line of therapy (LOT) was sorafenib (78%). The median time from HCC diagnosis to start of sorafenib was 43 days, and the median duration of sorafenib therapy was 60 days. Only 17% of patients received second LOT, and non-sorafenib treatment use increased to 66% (mostly chemotherapy combination). Transarterial chemoembolization was the most commonly observed locoregional therapy prior to the first LOT. The multivariable-adjusted average all-cause total cost among sorafenib treated patients was $17,642 (95% CI: $16,711-$18,558) per-patient per-month), of which $11,393 were HCC-specific. CONCLUSIONS: In patients who received first-line therapy for HCC, the duration of therapy was short (potentially due to progression or tolerability). Most patients did not continue to second-line therapy. Despite the short duration of therapy, HCC patients still incur a high economic burden, and there is a need for more effective and tolerable treatments.

Treatment Patterns Among Patients with Multiple Sclerosis Initiating Second-Line Disease-Modifying Therapy.

OBJECTIVE: Disease-modifying therapies (DMTs) can reduce multiple sclerosis (MS) relapse rates; however, effectiveness of treatments may vary. It is important to understand real-world treatment patterns in the context of MS relapses. We describe MS relapses related to treatment patterns among patients who switch treatment after their first DMT. METHODS: IBM MarketScan research databases were used to identify adult patients with MS who switched DMTs (index-first switch) after being newly treated with a DMT from January 2009 through March 2017, with 12 months of continuous enrollment pre- and post-index. Non-persistence was defined as discontinuing (at least 60 days without DMT) or switching DMTs. MS relapses were defined using a validated claims-based algorithm. Multivariable analysis was used to examine odds of 12-month persistence, odds of post-index relapse, and number of relapses. RESULTS: In total, 4121 patients with MS met all inclusion criteria (mean age 46.4 years; female 76.2%). Overall, 49.6% switched to an oral DMT, 36.5% to an injectable DMT, and 13.9% to an infusion DMT. Switching DMTs resulted in a 32.4% reduction in relapses between pre- and post-index. Only 54.6% of patients were persistent throughout the first year. Patients who switched to oral DMTs had 95% higher adjusted odds of persistence and 18% lower adjusted odds of a post-index period relapse than patients who switched to injectable DMTs. The number of baseline relapses was not associated with persistence but with 68% higher odds of a post-index relapse, with each additional baseline relapse associated with a 44% increase in number of post-index relapses. CONCLUSIONS: Among patients with MS who switched DMTs, persistence was consistently low regardless of treatment. Although persistence with oral DMTs was slightly higher than with injectable DMTs, overall results indicate poor persistence to second-line therapy and highlight the need to improve long-term persistence with DMTs.

Real-world treatment patterns, healthcare resource utilisation and costs in patients with systemic lupus erythematosus treated with belimumab: a retrospective analysis of claims data in the USA.

Objective: To examine the effects of belimumab initiation on healthcare resource utilisation (HCRU) and costs in SLE. Methods: This retrospective observational cohort study used healthcare administrative claims data from the IBM MarketScan Commercial Claims and Encounters Database to identify patients with SLE billing codes who received ≥1 intravenous belimumab infusion between March 2011 and December 2015. The first belimumab administration was the 'index date'. During the 6-month postindex period, nine belimumab infusions were recommended: three during the initiation period and six during the maintenance period. HCRU and cost data for inpatient admissions, emergency department visits, physician office visits, hospital-based outpatient visits, laboratory services, other outpatient services and outpatient pharmacy prescriptions were compared in the 6-month pre/postindex periods. Results: Of the 1879 patients with SLE included, 43% received ≥3 intravenous initiation administrations. An average of 5.3 (SD: 2.4) of the nine recommended belimumab administrations were received within 6 months. In the 6-month preindex versus postindex periods, significant reductions were noted for inpatient hospitalisations (18% vs 9%, p<0.001; mean visits: 0.3 vs 0.14, p<0.001) and emergency department visits (40% vs 24%, p<0.001; mean visits; 3.53 vs 1.96, p<0.001). Mean total costs were higher in the 6-month postindex versus preindex period ($41 426 vs $29 270; p<0.001). Conclusions: In this study of real-world intravenous belimumab for SLE, adherence to recommended infusion schedules was low. Outpatient healthcare and associated costs were higher in the 6 months after belimumab was initiated, although inpatient costs were lower. Reasons for non-adherence with belimumab and implications should be investigated.

Care Among Migraine Patients in a Commercially Insured Population.

INTRODUCTION: Migraine management is characterized by the poor use of preventive therapy and the overuse of acute medications. An analysis of current treatment patterns in migraineurs is needed to improve care in this patient population. The aim of this study was to describe treatment patterns and healthcare utilization of newly diagnosed migraine patients. METHODS: This was a retrospective observation study of newly diagnosed migraine patients (no indication of migraine in the past year) identified in the IBM MarketScan Commercial Claims and Encounters database from 1 January 2010 to 30 June 2014. The final study population comprised persons aged 18-64 years at index (new diagnosis of migraine) with 12 months of continuous enrollment in an insurance plan with medical and pharmacy benefits pre-index and post-index. Treatment patterns and healthcare resource utilization were assessed during the post-index period (at least 12-months). RESULTS: Of the 1,588,666 migraine patients identified in the database as potentially eligible to participate in the study, 284,719 (17.9%) met the final inclusion criteria. Patients generally used acute and preventive therapies to manage migraine attacks, with most patients using preventive therapy (59.1%). However, 67.9% of those using preventive therapy discontinued the current therapy, with a median time to discontinuation of 5 months. Most of the patients who discontinued preventative therapy also used an acute treatment to manage migraine attacks after discontinuation (77.6%), generally in the year following discontinuation (68.4%). Patients on acute therapies were found to use triptans excessively (1.6%) and other non-migraine-specific acute medications for treatment (7.1%). Acute patients were also at risk of opioid dependence (12.0%) and commonly received opioids or barbiturates as first-line therapy (34.1%). CONCLUSION: Newly diagnosed migraine patients are not being properly treated, as indicated by their excessive use of acute therapies and short time on preventive treatment before discontinuation of that treatment. Further study of the reasons why patients discontinue preventive therapy (adverse events, no response, etc.) and continue to excessively use acute treatments once their treatment regimen has been established is needed.

Real-world analysis of cost, health care resource utilization, and supportive care in Hodgkin lymphoma patients with frontline failure.

PURPOSE: The purpose of this study was to evaluate the economic burden of frontline failure (FLF) among classical Hodgkin lymphoma (HL) patients during and after treatment. PATIENTS AND METHODS: The population consisted of adult HL patients identified from January 2010 through September 2015 without any other primary cancer prior to HL diagnosis, who also had a frontline (FL) regimen indicative of curative intent. Patients were characterized as FLF (those who restart, switch to any chemotherapy; had a hematopoietic stem cell transplant; or newly initiated radiation therapy [RT] after discontinuing FL) or non-FLF (those not considered as FLF). Direct health care utilization and expenditures were measured over both fixed and variable length follow-up periods and during FL therapy. RESULTS: There were 77 FLF and 602 non-FLF patients who met the final inclusion criteria. FLF and non-FLF patients were demographically similar with mean age 38.5 years and 47.5% females. Average per patient per month (PPPM) costs were significantly higher for FLF patients during all follow-up (US$20,266 vs US$7,772, P<0.05). Annual total expenditures were significantly higher among FLF patients (US$198,388) vs non-FLF patients (US$37,549). FLF (vs non-FLF) patients had a significantly shorter duration of FL therapy (116 vs 131 days, P=0.024) and higher total PPPM expenditures during FL (US$29,040 vs US$16,369, P<0.05). Annual cost varied by failure type with those who failed due to restart incurring the highest cost (US$269,189) and those who switched incurring the lowest cost (US$46,951). FLF patients had a significantly greater utilization in every health care resource category during follow-up. CONCLUSION: FLF (vs non-FLF) patients utilized substantially more health care resources and incurred a substantially higher economic burden. Over 5 years, FLF patients with at least two lines of treatment were projected to incur US$535,846 of health care costs. Further research is needed to determine optimal treatment that could reduce the risk of progression, need for treatment after FL, and enhance long-term clinical and economic outcomes.

Melanoma complicating treatment with natalizumab for multiple sclerosis: A report from the Southern Network on Adverse Reactions (SONAR).

A 43-year-old female with multiple sclerosis developed urethral melanoma. The only potential risk factor was treatment with natalizumab, a humanized monoclonal antibody against α4 integrins. To investigate the risk-exposure relationship, we reviewed this case, all other published cases, and cases of natalizumab-associated melanoma reported to regulatory agencies. Data sources included the Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) (2004-2014), a FDA Advisory Committee Meeting Report, and peer-reviewed publications. In the United States, the manufacturer maintains an FDA-mandated Tysabri Safety Surveillance Program (part of the Tysabri Outcomes Unified Commitment to Health (TOUCH)) of natalizumab-treated patients. We statistically compared reporting completeness for natalizumab-associated melanoma cases in FAERs for which information was obtained entirely from the TOUCH program versus cases where FAERS information was supplemented by TOUCH program information. FAERS included 137 natalizumab-associated melanoma reports in patients with multiple sclerosis. Median age at melanoma diagnosis was 45 years (range: 21-74 years). Changes in preexisting nevi occurred in 16%, history of cutaneous nevi occurred in 22%, diagnosis within 2 years of beginning natalizumab occurred in 34%, and 74% had primary surgical treatment. Among seven natalizumab-treated MS patients who developed biopsy-confirmed melanoma on treatment and reported in the literature, median age at diagnosis was 41 years (range: 38-48 years); and the melanoma diagnosis occurred following a median of 12 natalizumab doses (range: 1-77 doses). A history of mole or nevi was noted in four patients and a history of prior melanoma was noted in one patient. Completeness scores for reports were significantly lower for FAERS cases reported from the TOUCH program versus FAERS cases supplemented by TOUCH information (median score of 2 vs. 4 items out of 8-possible items, P < 0.0007). Clinicians should monitor existing nevi and maintain suspicion for melanoma developing in natalizumab-treated patients. The TOUCH Safety Surveillance Program, currently focused on progressive multifocal leukoencephalopathy, should be expanded to include information on other serious complications including malignancies, particularly if they are immunologic in nature.

Tale of Two Erythropoiesis-Stimulating Agents: Utilization, Dosing, Litigation, and Costs of Darbepoetin and Epoetin Among South Carolina Medicaid-Covered Patients With Cancer and Chemotherapy-Induced Anemia.

PURPOSE: The US Food and Drug Administration (FDA) has approved epoetin and darbepoetin for chemotherapy-induced anemia (CIA). Approved epoetin and darbepoetin dosing schedules were three times per week and weekly, respectively, although off-label, less frequent scheduling was common. In 2004, 2007, and 2008, a US Food and Drug Administration Advisory Committees warned of risks associated with erythropoiesis-stimulating agents. During this period, lawsuits alleging illegal darbepoetin marketing practices have concluded, resulting in $1.1 billion in fines and settlements and one criminal conviction. No prior study, to our knowledge, has reported on the use of darbepoetin versus epoetin for CIA. METHODS: We evaluated the dosing, utilization, and costs of erythropoiesis-stimulating agents among 3,761 South Carolina Medicaid patients with CIA. RESULTS: Epoetin and darbepoetin utilization rates were 22% and 28% in 2003, 10% and 33% in 2007, and 3% and 7% in 2010, respectively. Mean per-patient per-administration epoetin and darbepoetin doses were 40,983 IU and 191 µg, respectively, in 2003 and 47,753 IU and 369 µg, respectively, in 2010. Mean monthly patient costs for epoetin and darbepoetin were $1,030 and $981, respectively, in 2003 and $932 and $1,352, respectively, in 2010. Epoetin use decreased steadily between 2002 and 2010; darbepoetin use increased steadily between 2003 and 2007 and then decreased steadily thereafter. Per-patient dosing of darbepoetin, but not epoetin, increased steadily between 2003 and 2010, and monthly per-patient epoetin costs decreased 3% while the per-patients costs of darbepoetin increased 30% between 2003 and 2010. CONCLUSION: To our knowledge, our findings are the first data reporting on epoetin versus darbepoetin use for CIA and support recently concluded lawsuits involving allegations of illegal marketing practices of the manufacturer of darbepoetin.

Venue of receiving diabetes self-management education and training and its impact on oral diabetic medication adherence.

AIMS: To determine predictors associated with the diabetes self-management education and training (DSME) venue and its impact on oral antidiabetic (OAD) medication adherence. METHODS: The Medical Expenditure Panel Survey household component (MEPS-HC) data (2010-2012) identified adults with diabetes prescribed OAD medication(s) who completed a supplemental Diabetes Care Survey (DCS). Based on the DCS responses to questions about the number and type of DSME venue(s), two groups were created: (1) multiple venues (a physician or health professional plus internet and/or group classes) vs (2) single venue (physician or health professional only). The medication possession ratio (MPR) measured medication adherence, with 0.80 the cut-point defining adherent. Logistic regression examined factors associated with the DSME venue and its effect on OAD medication adherence. RESULTS: Of the 2119 respondents, 41.6% received DSME from multiple venues. Age (<65years), education-level (college or higher), high-income, and diet modification were significantly more likely associated with receiving DSME from multiple venues. In single vs multiple venues, medication adherence was suboptimal (mean MPR 0.66 vs 0.64, p=0.245), and venue showed no influence on adherence (OR: 0.92, 95% CI, 0.73-1.16). CONCLUSION: Sociodemographic characteristics influence where adults with diabetes receive DSME. Adding different DSME venues may not address suboptimal OAD medication adherence.

Fluoroquinolone-related neuropsychiatric and mitochondrial toxicity: a collaborative investigation by scientists and members of a social network.

BACKGROUND: The 3 fluoroquinolone (FQ) antibiotics - ciprofoxacin, levofoxacin, and moxifoxacin - are commonly administered to oncology patients. Although these oral antibiotics are approved by the US Food and Drug Administration (FDA) for treatment of urinary tract infections, acute bacterial sinusitis, or bacterial infection in patients with chronic obstructive pulmonary disease, they are commonly prescribed off-label to neutropenic cancer patients for the prevention and treatment of infections associated with febrile neutropenia. New serious FQ-associated safety concerns have been identified through novel collaborations between FQ-treated persons who have developed long-term neuropsychiatric (NP) toxicity, pharmacovigilance experts, and basic scientists. OBJECTIVE: To conduct basic science and clinical investigations of a newly identified adverse drug reaction, termed FQ-associated disability. METHODS: 5 groups of C57BL/6 mice receiving the antibiotic ciprofoxacin in 10-mg increments (10 mg/kg-50 mg/kg) and 1 group of control mice were evaluated. The Southern Network on Adverse Reactions (SONAR) and a social network of FQ-treated persons with long-term NP toxicity (the Floxed Network) conducted a web-based survey. The clinical toxicity manifestations reported by 94 respondents to the web-based survey of persons who had received 1 or more doses of an FQ prescribed for any indication (generally at FDA-approved dosages) and who subsequently experienced possible adverse drug reactions were compared with adverse event information included on the product label for levofoxacin and with FQ-associated adverse events reported to the FDA's MedWatch program. RESULTS: Mice treated with ciprofoxacin had lower grip strengths, reduced balance, and depressive behavior compared with the controls. For the survey, 93 of 94 respondents reported FQ-associated events including anxiety, depression, insomnia, panic attacks, clouded thinking, depersonalization, suicidal thoughts, psychosis, nightmares, and impaired memory beginning within days of FQ initiation or days to months of FQ discontinuation. The FDA Adverse Event Reporting System (FAERS) included 210,705 adverse events and 2,991 fatalities for FQs. Levofoxacin and ciprofoxacin toxicities were neurologic (30% and 26%, respectively), tendon damage (8% and 6%), and psychiatric (10% and 2%). In 2013, an FDA safety review reported that FQs affect mammalian topoisomerase II, especially in mitochondria. In 2013 and 2014, SONAR fled citizen petitions requesting black box revisions identifying neuropsychiatric toxicities and mitochrondrial toxicity as serious levofoxacin-associated adverse drug reactions. In 2015, FDA advisors recommended that FQ product labels be revised to include information about this newly identified disability syndrome termed "FQ-associated disability" (FQAD). LIMITATIONS: Basic science studies evaluated NP toxicity for only 1 FQ, ciprofoxacin. CONCLUSION: Pharmacovigilance investigators, a social network, and basic scientists can collaborate on pharmacovigilance investigations. Revised product labels describing a new serious adverse drug reaction, levofoxacin-associated long-term disability, as recommended by an FDA advisory committee, are advised.

Patterns of use and health expenses associated with triptans among adults with migraines.

OBJECTIVES: To determine patterns of use, socioeconomic factors, and the impact on total health expenses associated with triptan therapy among patients with migraines. MATERIALS AND METHODS: Patients with migraines were identified from the Medical Expenditure Panel Survey household component files (2006 to 2011) and were restricted to those who were 18 years or older and had a migraine diagnosis. The major outcome measures were triptan use during the 2-year period and annualized average total and migraine-related health care expenses and medical utilization. Socioeconomic factors associated with triptan use were analyzed by using logistic regression. The impact of triptan use on total and migraine-related health expenses was assessed by linear regression models with log transformations. RESULTS: Among 1961 patients with a migraine diagnosis (representing 45.6 million individuals in the United States for years 2006 to 2011), 501 received triptans to treat acute migraines (representing 13.1 million individuals in the United States, 28.6%). Patients who were females and had higher income and education levels were more likely to receive triptans to treat migraines. Triptan expense accounted for 49.6% of total migraine-related expenses and 21.9% of total all-cause prescription drug expenses respectively. Compared with nontriptan users, the annualized total health expenses increased by 19.7% in triptan users after adjusting for demographic and health-related variables. DISCUSSION: The study suggested that socioeconomic factors were associated with triptan use in migraineurs. Higher total and migraine-related health expenses were observed in triptan users.

Patterns of use and expenses associated with mail-service pharmacy in adults with diabetes.

OBJECTIVES: To identify socioeconomic factors associated with mail-service pharmacy use and compare the differences in disease-specific prescription medication and medical utilization expenses in a nationally representative sample of adults with diabetes. DESIGN: A retrospective, longitudinal, cross-sectional study. SETTING: United States in 2006-11. PARTICIPANTS: Medical Expenditure Panel Survey household component (MEPS-HC) participants aged 18 years or older diagnosed with diabetes and prescribed antidiabetic medications. MAIN OUTCOME MEASURES: Likelihood of mail-service pharmacy use, diabetes-related medical utilization, and medication expenses. RESULTS: Among 4,430 eligible participants identified in the 2006-11 surveys, representing more than 83 million U.S. individuals, nearly 13% of the participants obtained two-thirds or more of their antidiabetic medications via mail service predominantly. Mail-service pharmacy users were older, had high school or college degrees, had higher incomes, and were more likely to be covered by private insurance. There were no significant differences in diabetes-related medical utilization and drug expenses between the two groups. CONCLUSION: Besides pharmacy benefit design, sociodemographic and economic factors influenced drug dispensing channel use (mail service versus community pharmacy). No significant differences in diabetes-related drug and medical expenses between mail-service and community pharmacy users were observed.