Greater need for treatment optimization in patients with epilepsy initiating adjunctive therapy: Results of a retrospective claims analysis of antiseizure medication drug load in the United States.

BACKGROUND: This retrospective, observational study used US claims data to assess changes in antiseizure medication (ASM) drug load for a cohort of patients with epilepsy. METHODS: Adults (≥18 years) with a diagnosis of epilepsy (ICD-10 code G40.xxx) who started new adjunctive ASM treatment with one of 4 branded (brivaracetam, eslicarbazepine, lacosamide, perampanel) or 4 unbranded (carbamazepine, lamotrigine, levetiracetam, topiramate) ASMs between January 1, 2016 and December 31, 2020 were identified from IBM MarketScan® research databases (primary study population). Patients must have been continuously enrolled 360 days before the start of the new ASM (eligibility period). Follow-up was from the start of new ASM until Day 540 (∼18 months). The primary endpoint was concomitant ASM drug load, which included all ASMs except the new (comparator) ASM. A sensitivity analysis population included adults with epilepsy who were continuously enrolled for ≥ 180 days during at least one calendar year in the study period (2016-2020), whether or not the comparator ASM was new or existing during that period. Total ASM drug load, which included comparator ASM and concomitant ASMs, was assessed in the sensitivity analysis population. RESULTS: In total, 21,332 patients were included in the primary study population, of which 5767 initiated branded ASMs and 15,565 initiated unbranded ASMs. A total of 392,426 patients were included in the sensitivity analysis population during at least one calendar year 2016-2020. Concomitant ASM drug load increased in the 360 days prior to new ASM start and slightly declined thereafter. Mean concomitant ASM drug load for the primary population was 1.6 (SD 1.8) at new ASM start. Concomitant drug load was higher among those starting branded ASM comparators compared to those starting unbranded comparators. Mean total ASM drug load for patients increased over time and was approximately double for patients exposed to branded ASMs (mean range 2.1 to 2.7) compared to that of patients exposed to any unbranded ASM (mean range 1.0 to 1.3). CONCLUSION: Concomitant ASM drug load increased prior to addition of new ASM, with higher increases observed among patients starting branded vs unbranded ASMs, followed by slight decreases thereafter. Total drug load increased linearly among all patients. These findings underscore the need for ongoing ASM regimen evaluation and treatment optimization in patients with epilepsy.

Seeking Repeating Anthropogenic Seismic Sources: Implications for Seismic Velocity Monitoring at Fault Zones.

Seismic velocities in rocks are highly sensitive to changes in permanent deformation and fluid content. The temporal variation of seismic velocity during the preparation phase of earthquakes has been well documented in laboratories but rarely observed in nature. It has been recently found that some anthropogenic, high-frequency (>1 Hz) seismic sources are powerful enough to generate body waves that travel down to a few kilometers and can be used to monitor fault zones at seismogenic depth. Anthropogenic seismic sources typically have fixed spatial distribution and provide new perspectives for velocity monitoring. In this work, we propose a systematic workflow to seek such powerful seismic sources in a rapid and straightforward manner. We tackle the problem from a statistical point of view, considering that persistent, powerful seismic sources yield highly coherent correlation functions (CFs) between pairs of seismic sensors. The algorithm is tested in California and Japan. Multiple sites close to fault zones show high-frequency CFs stable for an extended period of time. These findings have great potential for monitoring fault zones, including the San Jacinto Fault and the Ridgecrest area in Southern California, Napa in Northern California, and faults in central Japan. However, extra steps, such as beamforming or polarization analysis, are required to determine the dominant seismic sources and study the source characteristics, which are crucial to interpreting the velocity monitoring results. Train tremors identified by the present approach have been successfully used for seismic velocity monitoring of the San Jacinto Fault in previous studies.

Monitoring Seismic Velocity Changes Across the San Jacinto Fault Using Train-Generated Seismic Tremors.

Microseismic noise has been used for seismic velocity monitoring. However, such signals are dominated by low-frequency surface waves that are not ideal for detecting changes associated with small tectonic processes. Here we show that it is possible to extract stable, high-frequency body waves using seismic tremors generated by freight trains. Such body waves allow us to focus on small velocity perturbations in the crust with high spatial resolution. We report on 10 years of seismic velocity temporal changes at the San Jacinto Fault. We observe and map a two-month-long episode of velocity changes with complex spatial distribution and interpret the velocity perturbation as produced by a previously undocumented slow-slip event. We verify the hypothesis through numerical simulations and locate this event along a fault segment believed to be locked. Such a slow-slip event stresses its surroundings and may trigger a major earthquake on a fault section approaching failure.

Incidence of mental health conditions by seizure control among adults with epilepsy in the United States.

BACKGROUND: Mental health conditions (MHCs) are frequent comorbidities among people with epilepsy; however, the influence of seizure control on the incidence of MHCs is not well reported. This retrospective observational cohort study based on claims data evaluated the effects of indicators of poor seizure control on the incidence of MHCs among MHC-naïve people with epilepsy. We hypothesized that poor seizure control is associated with new-onset MHC diagnoses and/or new prescription drugs for MHCs. METHODS: This study utilized a sample of patients from HealthVerity Marketplace, which includes more than 150 US commercial, Medicare, and Medicaid payers, to identify a cohort of adults (age ≥18 years) with prevalent epilepsy. Follow-up started on day 1 (January 1) after a 1-year eligibility assessment period occurring in calendar year 2017 or 2018. Patients were followed up until the occurrence of an incident MHC event (primary outcome), defined as a mental health diagnosis or psychotropic drug prescription. Time from follow-up to incident MHC diagnosis or to a drug prescription specific to depression or anxiety disorder was analyzed as a secondary outcome. Multivariate Cox proportional hazards regressions were estimated with time-varying covariates, measured in 6-month intervals during follow-up. Time-varying covariates were based on the occurrence of 4 variables used as indicators of poor seizure control in the prior period: epilepsy-related emergent care admissions, epilepsy-related inpatient admissions, epilepsy electroencephalography referrals, and exposure to one or more new antiseizure medications (ASMs). RESULTS: From a random sample of 40,000 people with epilepsy, 2563 (mean age 46.1 years; 50.6% male) were included in the analysis. Incident MHC events were observed in 27.7% (incidence rate 24.4 events per 100 person-years over 2,915.7 total person-years of follow-up). Mean (standard deviation [SD]) time to event was 232.7 (186.3) days. Among the 4 variables, epilepsy-related emergent care admissions were associated with an increased risk of incident MHC events in the following 6-month period (hazard ratio [HR] = 1.676, 95% confidence interval [CI]: 1.386, 2.026, p < 0.001) as were prescriptions for new ASMs in the previous period (HR = 1.702, 95% CI: 1.359, 2.132, p < 0.001). Previous epilepsy-related emergent care admissions (HR = 1.650, 95% CI: 1.347, 2.021, p < 0.001) and new ASMs (HR = 1.632, 95% CI: 1.280, 2.081, p < 0.001) also predicted an increased risk of incident depression or anxiety in the following 6-month period. CONCLUSIONS: Previous indicators of poor seizure control, including epilepsy-related emergent care admissions and new ASMs, predicted increased risk of new MHC events, including depression and anxiety, during the following 6-month interval in MHC-naïve patients with prevalent epilepsy. These data suggest that poor seizure control can increase the subsequent risk of new mental health diagnoses and treatment among people with epilepsy.

Indirect treatment comparison of cenobamate to other ASMs for the treatment of uncontrolled focal seizures.

OBJECTIVE: The efficacy and safety of cenobamate relative to other antiseizure medications (ASMs) has not been evaluated. An indirect treatment comparison (network meta-analysis) was performed to determine if adjunctive cenobamate increases the odds ratio (OR) for ≥50% responder rate or for withdrawals due to treatment-emergent adverse events (TEAEs) leading to ASM discontinuation versus adjunctive therapy with other ASMs. METHODS: A systematic literature review was conducted to identify randomized, double-blind, placebo-controlled trials (maintenance phase ≥ 12 weeks) assessing adjunctive ASMs in adults with uncontrolled focal seizures. Cenobamate was compared to a group of seven other ASMs, and to subgroups of branded (brivaracetam, eslicarbazepine acetate, lacosamide, and perampanel) and older (lamotrigine, levetiracetam, and topiramate) ASMs at FDA-recommended daily maintenance doses (FDA-RDMD), at all doses, and at maximum and minimum daily doses. Statistical significance was set at p < 0.05. RESULTS: Twenty-one studies were eligible for analysis. The placebo-adjusted ≥ 50% responder rate for FDA-RDMD of cenobamate was superior (OR 4.200; 95% CI 2.279, 7.742) to FDA-RDMD of all seven assessed (OR 2.202 95% CI 1.915, 2.532; p = 0.044) and branded ASMs (OR 2.148; 95% CI 1.849, 2.494; p = 0.037). There was no significant difference for ≥50% responder rate between FDA-RDMD of cenobamate and FDA-RDMD of older ASMs (OR 2.617; 95% CI 1.767, 3.878; p = 0.202). No significant differences were identified for ≥50% responder rate when comparing all doses and maximum/minimum doses of cenobamate to all seven, branded, and older ASMs. Cenobamate demonstrated comparable TEAE withdrawal rates to all seven ASMs, branded ASMs, and older ASMs across each of the four dose ranges (all p > 0.05). SIGNIFICANCE: Patients receiving FDA-RDMD of cenobamate were more likely to have ≥50% seizure reduction compared with FDA-RDMD of the seven assessed ASMs and branded ASMs, without an increase in treatment discontinuation due to TEAEs.

Measurement of lead complexation by humic acids and humic acid analogues using competitive ligand exchange.

In soil and water, metal complexation by humic substances has been demonstrated to have great importance in determining the bioavailability of many trace metals including lead. The binding of lead by humic acids has important implications for lead toxicity, and remediation. In this study we demonstrate the use of 4-(2-pyridylazo)-resorcinol (PAR) as a competitive ligand for the purposed of determining sorption isotherms for Pb2+ on humic acids and humic acid analogs. Equilibration rates at pH 8 were very rapid and the sorption isotherms measured were fit to the Langmuir isotherm equation and values for the stability constants (KHA) and complexing site concentrations (Lt) are reported. At a PAR concentration of 0.24 mM and humic acid concentrations of 25-200 mg/L, the mass normalized log KHA values for the humic substances ranged from 7.2 to 7.9, while the log Lt values ranged from -2.8 to -3.8. At lower PAR concentrations both KHA and Lt tended to increase in magnitude indicating the role of the PAR concentration in establishing the measurement window for the interaction of Pb2+ with humic materials.

Seismic Stereometry Reveals Preparatory Behavior and Source Kinematics of Intermediate-Size Earthquakes.

Although moderate-size earthquakes are poorly studied by lack of near-fault observations, they can provide key information about larger damaging earthquakes. Here we propose a new approach, inspired by double-difference relocation, that uses high-coherency waveforms recorded at neighboring sensors, to study the preparation phase and dynamics of moderate-size earthquakes. We validate this technique by analyzing the 2016, M w 5.2 Borrego Springs earthquake in Southern California and find consistent rupture velocities of 2 km/s highlighting two main rupture asperities. The analysis of the 2019, Ml5.2 Le Teil earthquake in France reveals slow nucleation at depth that migrates to the surface and propagates northward with a velocity of ∼2.8 km/s, highlighting two main rupture events also imaged by InSAR. By providing unprecedented resolution in our observation of the rupture dynamics, this approach will be useful in better understanding the preparation phase and rupture of both tectonic and induced earthquakes.

Aqueous solubility of beryllium(II) at physiological pH: effects of buffer composition and counterions.

Beryllium ion elicits p53-mediated cell cycle arrest in some types of human cancer cells, and it is a potent inhibitor of GSK3 kinase activity. Paradoxically, Be2+ is regarded to have almost negligible aqueous solubility at physiological pH, due to precipitation as Be(OH)2. This study demonstrates that the interaction of Be2+ with serum proteins greatly increases its effective solubility. In typical serum-supplemented mammalian cell culture medium, Be2+ was soluble up to about 0.5 mM, which greatly exceeds the concentration needed for biological activity. Some biochemical studies require protein-free Be2+ solutions. In such cases, the inclusion of a specific inorganic counterion, sulfate, increased solubility considerably. The role of sulfate as a solubility-enhancing factor became evident during preparation of buffered solutions, as the apparent solubility of Be2+ depended on whether H2SO4 or a different strong acid was used for pH adjustment. The binding behavior of Be2+ observed via isothermal titration calorimetry was affected by the inclusion of sodium sulfate. The data reflect a "Diverse Ion Effect" consistent with ion pair formation between solvated Be2+ and sulfate. These insights into the solubility behavior of Be2+ at physiological and near-physiological pH will provide guidance to assist sample preparation for biochemical studies.

Train Traffic as a Powerful Noise Source for Monitoring Active Faults With Seismic Interferometry.

Laboratory experiments report that detectable seismic velocity changes should occur in the vicinity of fault zones prior to earthquakes. However, operating permanent active seismic sources to monitor natural faults at seismogenic depth is found to be nearly impossible to achieve. We show that seismic noise generated by vehicle traffic, and especially heavy freight trains, can be turned into a powerful repetitive seismic source to continuously probe the Earth's crust at a few kilometers depth. Results of an exploratory seismic experiment in Southern California demonstrate that correlations of train-generated seismic signals allow daily reconstruction of direct P body waves probing the San Jacinto Fault down to 4-km depth. This new approach may facilitate monitoring most of the San Andreas Fault system using the railway and highway network of California.

What Contributes Most to High Health Care Costs? Health Care Spending in High Resource Patients.

BACKGROUND: U.S. health care spending nearly doubled in the decade from 2000-2010. Although the pace of increase has moderated recently, the rate of growth of health care costs is expected to be higher than the growth in the economy for the near future. Previous studies have estimated that 5% of patients account for half of all health care costs, while the top 1% of spenders account for over 27% of costs. The distribution of health care expenditures by type of service and the prevalence of particular health conditions for these patients is not clear, and is likely to differ from the overall population. OBJECTIVE: To examine health care spending patterns and what contributes to costs for the top 5% of managed health care users based on total expenditures. METHODS: This retrospective observational study employed a large administrative claims database analysis of health care claims of managed care enrollees across the full age and care spectrum. Direct health care expenditures were compared during calendar year 2011 by place of service (outpatient, inpatient, and pharmacy), payer type (commercially insured, Medicare Advantage, and Medicaid managed care), and therapy area between the full population and high resource patients (HRP). RESULTS: The mean total expenditure per HRP during calendar year 2011 was $43,104 versus $3,955 per patient for the full population. Treatment of back disorders and osteoarthritis contributed the largest share of expenditures in both HRP and the full study population, while chronic renal failure, heart disease, and some oncology treatments accounted for disproportionately higher expenditures in HRP. The share of overall expenditures attributed to inpatient services was significantly higher for HRP (40.0%) compared with the full population (24.6%), while the share of expenditures attributed to pharmacy (HRP = 18.1%, full = 21.4%) and outpatient services (HRP = 41.9%, full = 54.1%) was reduced. This pattern was observed across payer type. While the use of physician-administered pharmaceuticals was slightly higher in HRP, their use did not alter this spending pattern. CONCLUSIONS: Overall, expenditures in the HRP population are more than 10-fold higher compared with the full population. Managed care pharmacy can benefit from understanding what contributes to these higher costs, and managed care directors should consider an appropriately balanced assessment of the share of total spend by service and therapeutic category in HRP when devising drug usage and related cost-management strategies.

Comparative healthcare costs in patients with metastatic melanoma in the USA.

Recent advances have increased treatment options for, and improved clinical outcomes in, metastatic melanoma (mM). Using a large claims database, this retrospective study compared healthcare and adverse event (AE) costs in a US managed care population of mM patients initiating vemurafenib (VEM), ipilimumab (IPI), dacarbazine (DTIC), paclitaxel (PAC), or temozolomide (TMZ) from July 2009 to September 2012. Treatment episodes were identified from the start of study drugs (index date) to a switch to a different study drug, or a gap greater than 45 days (>112 days for IPI). Grade 3/4 adverse events occurring ≥5% from study drug package inserts were selected for this analysis. All-cause costs for treatment episodes and AEs were normalized as monthly costs. Generalized estimating equation models with log link and gamma distribution provided adjusted monthly treatment episode and AE costs. A total of 809 treatment episodes were identified in 541 mM patients, with a mean (SD) age of 57.5 (11.5) years. The total mean (SD) all-cause cost per treatment episode for VEM was $77 687 ($60 329), for IPI was $153 062 ($134 048), for DTIC was $35 243 ($33 641), for TMZ was $42 870 ($41 384), and for PAC was $58 991 ($81 306). The adjusted mean monthly treatment episode cost for VEM was significantly lower than that for IPI and comparable to that for other drugs. VEM had a significantly lower monthly AE cost than IPI, DTIC, and PAC. In combination with safety and efficacy findings, these results may assist clinicians, patients, policy makers, and payers in the treatment of mM.

Risk of tuberculosis, serious infection and lymphoma with disease-modifying biologic drugs in rheumatoid arthritis patients in Taiwan.

AIM: To determine the risk of adverse events in rheumatoid arthritis (RA) patients treated with biological disease-modifying anti-rheumatic drugs (bDMARD) versus traditional DMARDs (tDMARD). METHOD: This retrospective study used Taiwan's National Health Insurance Research Database to capture data for adult patients diagnosed with RA between 1 January 1999 and 31 December 2009 and treated with tDMARD or bDMARD. The endpoints were patients with cases of an inpatient serious bacterial infection (SBI), diagnosis of tuberculosis (TB) or lymphoma. Within the bDMARD cohort, individual bDMARDS with adequate data were also compared (adalimumab and etanercept). Propensity-score matching was used to adjust for significant (P ≤ 0.05) patient characteristics. Incidence rate ratios (IRR) of SBI/TB/lymphoma cases versus non-cases were adjusted for exposure time (rate per 100,000 patient-years) and 95% confidence intervals were constructed to assess whether IRRs differed from 1.0. RESULTS: Of 34,947 potential patients, 7888 tDMARD, 3459 bDMARD (including 1492 etanercept and 746 adalimumab) patients were matched for analysis. A total of 2150 cases were identified and of these 1711 were SBI, 406 as TB and 33 as lymphoma. For all cases except SBI, the IRR (95% CI) was higher for bDMARD versus tDMARD (SBI 1.04 [0.89-1.19]; TB 2.67 [2.12-3.34]; lymphoma 3.24 [1.37-7.06]). Excepting lymphoma, IRR was higher for adalimumab versus etanercept (SBI 1.83 [1.19-2.77]; TB 2.35 [1.29-4.15]; lymphoma 1.49 [0.03-18.66]). CONCLUSIONS: There was a higher risk for specified infections and lymphoma with bDMARD versus tDMARD and adalimumab versus etanercept.

Estimating effectiveness and cost of biologics for rheumatoid arthritis: application of a validated algorithm to commercial insurance claims.

PURPOSE: The aim of this analysis was to implement a claims-based algorithm to estimate biologic cost per effectively treated patient for biologics approved for moderate to severe rheumatoid arthritis (RA). METHODS: This retrospective analysis included commercially insured adults (aged 18-63 years) with RA in a commercial database, who initiated biologic treatment with abatacept, adalimumab, etanercept, golimumab, or infliximab between 2007 and 2010. The algorithm defined effectiveness as having all of the following: high adherence, no biologic dose increase, no biologic switching, no new nonbiologic disease-modifying antirheumatic drug, no increased or new oral glucocorticoid use, and no more than 1 glucocorticoid injection. For each biologic, cost per effectively treated patient was defined as total drug and administration costs (from allowed amounts on claims), divided by the number of patients categorized as effectively treated. FINDINGS: Of 15,351 patients, 12,018 (78.3%) were women, and the mean (SD) age was 49.7 (9.6) years. The algorithm categorized treatment as effective in the first year for 30% (1899/6374) of etanercept, 30% (1396/4661) of adalimumab, 20% (560/2765) of infliximab, 27% (361/1338) of abatacept, and 29% (62/213) of golimumab treated patients. The 1-year biologic cost per effectively treated patient, as defined by the algorithm, was nominally lower for subcutaneously injected biologics than for infused biologics. The 1-year biologic cost per effectively treated patient, as defined by the algorithm, was lowest for etanercept ($49,952), followed by golimumab ($50,189), adalimumab ($52,858), abatacept ($71,866), and infliximab ($104,333). IMPLICATIONS: Algorithm-defined effectiveness was similar for biologics other than infliximab. The 1-year biologic cost per effectively treated patient, as defined by the algorithm, was nominally lower for subcutaneously injected biologics than for infused biologics.

Fesoterodine prescription fill patterns and evaluation of the YourWay patient support plan for patients with overactive bladder symptoms and physicians.

BACKGROUND: Adherence with oral medication for overactive bladder syndrome is suboptimal. To improve adherence, the YourWay plan was developed to assist patients and health care providers in defining treatment expectations and facilitating communication. OBJECTIVE: To evaluate medication adherence among patients with overactive bladder syndrome enrolled in the YourWay patient support plan, patient adoption of behavioral interventions, patient satisfaction with the plan, and physician experience with the plan. METHODS: In this 13-week, single-arm, open-label, multicenter, noninterventional study, fesoterodine-naïve patients received a prescription for fesoterodine 4 or 8 mg and a packet including a 14-day fesoterodine sample, educational materials, and progress tracker. Patients registered for the YourWay plan, which included an educational resource kit, interactive voice-response calls, and optional online and mail support. The primary end point was the proportion of patients who filled a prescription for a ≥ 90-day supply of fesoterodine within 90 days of enrollment. Secondary end points were the proportion of patients who filled ≥ 1 prescription and ≥ 2 prescriptions (post hoc), patient evaluation of their experience and satisfaction with the YourWay plan, and differences between prescription fillers and nonfillers in plan adoption and assessment (post hoc). We surveyed an independent sample of physicians to assess their experience with YourWay. RESULTS: Of 500 study completers, 10.4% filled a prescription for a ≥ 90-day supply of fesoterodine. Of those filling a prescription, 26.2% filled ≥ 1 prescription and among those, 61.0% refilled their prescription at least once. Many behavioral recommendations were adopted by 82% to 94% of patients. Fillers were more likely to take fesoterodine as directed, whereas adoption of behavioral recommendations or plan satisfaction did not differ between fillers and nonfillers. Most patients reported that the plan was informative and feasible to implement, and that they were satisfied with various aspects of the plan. Physicians also reported positive experiences. CONCLUSION: Most patients adopted YourWay components and viewed the plan positively, although adherence remained a challenge.

Use of a validated algorithm to estimate the annual cost of effective biologic treatment for rheumatoid arthritis.

OBJECTIVES: To estimate biologic cost per effectively treated patient with rheumatoid arthritis (RA) using a claims-based algorithm for effectiveness. METHODS: Patients with RA aged 18-63 years in the IMS PharMetrics Plus database were categorized as effectively treated if they met all six criteria: (1) a medication possession ratio ≥80% (subcutaneous) or at least as many infusions as specified in US labeling (intravenous); (2) no biologic dose increase; (3) no biologic switch; (4) no new non-biologic disease-modifying anti-rheumatic drug; (5) no new or increased oral glucocorticoid; and (6) ≤1 glucocorticoid injection. Biologic cost per effectively treated patient was defined as total cost of the index biologic (drug plus intravenous administration) divided by the number of patients categorized by the algorithm as effectively treated. Similar methods were used for the index biologic in the second year and for a second biologic after a switch. RESULTS: Rates that the index biologic was categorized as effective in the first year were 31.0% etanercept (2243/7247), 28.6% adalimumab (1426/4991), 28.6% abatacept (332/1160), 27.2% golimumab (71/261), and 20.2% infliximab (474/2352). Mean biologic cost per effectively treated patient, per the algorithm, was $50,141 etanercept, $53,386 golimumab, $56,942 adalimumab, $73,516 abatacept, and $114,089 infliximab. Biologic cost per effectively treated patient, using this algorithm, was lower for patients who continued the index biologic in the second year and higher after switching. CONCLUSIONS: When a claims-based algorithm was applied to a large commercial claims database, etanercept was categorized as the most effective and had the lowest estimated 1-year biologic cost per effectively treated patient. This proxy for effectiveness from claims databases was validated against a clinical effectiveness scale, but analyses of the second year or the year after a biologic switch were not included in the validation. Costs of other medications were not included in cost calculations.

Treatment patterns following discontinuation of adalimumab, etanercept, and infliximab in a US managed care sample.

OBJECTIVES: Because clinical guidelines do not offer clear recommendations for treatment options after discontinuing a tumor necrosis factor (TNF) blocker, this study evaluated treatment patterns within 360 days after discontinuation of TNF-blocker treatment. METHODS: The IMS LifeLink Health Plan Claims database was used to identify patients diagnosed with rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis who received etanercept, adalimumab, or infliximab between January 1, 2005 and March 31, 2009. Discontinuation from index (first) TNF blocker was defined as switching to a different TNF blocker or a >45-day gap in therapy. Patients were categorized into mutually exclusive groups in descending order: (a) restart of index TNF blocker; (b) switch to another TNF blocker; (c) switch to a different biologic; (d) switch to nonbiologic therapy; or (e) no new treatment. RESULTS: Among 27,704 patients who initiated TNF-blocker therapy, 14,707 (53%) patients discontinued treatment over 1-3 years of follow-up. Within 360 days of discontinuing index TNF blocker, 53.4% of patients restarted index therapy: etanercept 59.9%, adalimumab 46.5%, and infliximab 43.1% (P < 0.001 for etanercept vs. adalimumab and infliximab). The majority of therapy restarts occurred within the first 3 months after discontinuation. Other patients switched to another TNF blocker: etanercept 17.1%, adalimumab 19.1% (P = 0.010 vs. etanercept), and infliximab 15.0% (P = 0.009 vs. etanercept). Switches from index TNF blocker to non-TNF-blocker biologic therapy were low: etanercept 1.9%, adalimumab 4.1%, and infliximab 10.7% (P < 0.001 for etanercept vs. adalimumab and infliximab). Switches from index TNF blocker to nonbiologic treatments were 5.4% for etanercept, 6.5% for adalimumab, and 6.9% for infliximab. CONCLUSIONS: Restarting of index TNF-blocker therapy occurs frequently after discontinuation, suggesting that long gaps in TNF-blocker therapy may be common. A significantly higher proportion of etanercept patients restarted their index TNF blocker within 3 months of discontinuation, compared with adalimumab and infliximab patients.

Costs of tumor necrosis factor blockers per treated patient using real-world drug data in a managed care population.

BACKGROUND: Several anti-inflammatory biologic medications are available in the United States for the treatment of moderate-to-severe rheumatoid arthritis, moderate-to-severe psoriasis, psoriatic arthritis, or ankylosing spondylitis. The tumor necrosis factor (TNF) blockers etanercept, adalimumab, and infliximab are approved for use in adults with any of these conditions, but predicting the annual costs of TNF-blocker treatment is complex due to differences in dosing schedules, treatment gaps, switching between TNF blockers, and dose escalation over time. OBJECTIVES: To estimate the annual cost per treated patient from the payer perspective for etanercept, adalimumab, or infliximab in adults with rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis. METHODS: Adults in the IMS LifeLink Health Plan Claims Database were analyzed if they had at least 1 claim for etanercept, adalimumab, or infliximab between February 1, 2008, and July 5, 2010, and were continuously enrolled for at least 180 days before (pre-index period) through 360 days after the index claim (the first TNF-blocker claim after 6 months of continuous enrollment in the study period). Patients had a diagnosis of rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis, or a combination of these conditions, in the pre-index period. Cost was based on dose and price using April 2012 wholesale acquisition cost. Costs of administration were included for the first subcutaneous dose (etanercept or adalimumab) for new patients and for every intravenous dose (infliximab). Total TNF-blocker drug and administration costs, including nonindex TNF-blocker costs among patients who switched treatments, were divided by number of patients to yield cost per treated patient for each index TNF blocker. Subgroup analyses included cost by condition and cost for patients who were new to TNF-blocker treatment (no index TNF-blocker claim in the pre-index period) or continuing TNF-blocker treatment. RESULTS: Of the 30,107 patients in the analysis, the majority received etanercept (15,488 patients; 51.4%), followed by adalimumab (8,959 patients; 29.8%) and infliximab (5,660 patients; 18.8%). Approximately 2 in 3 patients (18,897 patients) were continuing TNF-blocker treatment, including 66.0%, 52.6%, and 70.0% of patients in the etanercept, adalimumab, and infliximab groups, respectively. Across all indications, the annual TNF-blocker cost per treated patient was lowest for etanercept, followed by adalimumab and then infliximab, respectively: overall ($17,767, $19,272, and $24,273); new patients ($17,270, $17,959, and $21,482); and continuing patients ($18,203, $20,453, and $25,468). Cost by condition among all patients ranged from $14,838 to $20,251 for etanercept, from $18,051 to $20,233 for adalimumab, and from $22,939 to $28,519 for infliximab. Cost by condition was 3% to 31% greater for adalimumab than for etanercept (relative cost, 103% to 131%), except among patients with psoriasis (relative cost, 94%), and was 26% to 72% greater for infliximab than for etanercept (relative cost, 126% to 172%). Approximately 9% to 11% of patients in each group switched TNF blockers in the first year, and the costs of nonindex TNF blockers comprised 16.8% of the total cost for etanercept, 13.4% for adalimumab, and 6.9% for infliximab. CONCLUSIONS: In adult patients with rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis, or some combination of these conditions, etanercept had a lower cost per treated patient than adalimumab or infliximab, except in patients with psoriasis alone. In these patients, adalimumab had a lower cost per treated patient than etanercept or infliximab.

Analysis of mercury in rock varnish samples in areas impacted by coal-fired power plants.

Rock varnish is a manganese-iron rich coating that forms on rocks, most often in arid climates. To assess its utility as an environmental monitor of mercury contamination, cold vapor atomic absorption spectrometry (CVAAS) was used for analysis. Samples were collected in the fallout patterns of two coal-fired power plants in southern Nevada: the defunct Mohave Power Plant (MPP) and the operating Reid Gardner Power Plant (RGPP). The resultant Hg concentrations in rock varnishes were plotted as a function of the distance from each power plant. The highest concentrations of Hg occurred at locations that suggest the power plants are the main source of pollutants. In addition, past tracer plume studies carried out at MPP show that the highest tracer concentrations coincide with the highest rock varnish Hg concentrations. However, additional samples are required to further demonstrate that power plants are indeed the sources of mercury in varnishes.

Exenatide BID and liraglutide QD treatment patterns among type 2 diabetes patients in Germany.

OBJECTIVES: This study evaluated patient and prescriber characteristics, treatment patterns, average daily dose (ADD), and glycemic control of patients initiating glucagon-like peptide 1 (GLP-1) receptor agonists in Germany. METHODS: The LifeLink™ EMR-EU database was searched to identify patients initiating exenatide twice daily (BID) or liraglutide once daily (QD) during the index period (January 1, 2009-April 4, 2010). Eligible patients had ≥ 180 days pre-index history, ≥ 90 days post-index follow-up, and a pre-index type 2 diabetes diagnosis. Univariate tests were conducted at α=0.05. RESULTS: Six hundred and ninety-two patients were included (exenatide BID 292, liraglutide QD 400): mean (SD) age 59 (10) years, 59% male. Diabetologists prescribed liraglutide QD to a larger share of patients (65% vs 35% exenatide BID) than non-diabetologists (51% vs 49%). GLP-1 receptor agonist choice was not associated with age (p=0.282), gender (p=0.960), number of pre-index glucose-lowering medications (2.0 [0.9], p=0.159), pre-index HbA1c (8.2 [1.5%], p=0.231) or Charlson Comorbidity Index score (0.45 [0.78], p=0.547). Mean (SD) ADD was 16.7 mcg (9.2, label range 10-20 mcg) for exenatide BID and 1.4 mg (0.7, label range 0.6-1.8 mg) for liraglutide QD. Among patients with post-index HbA1c tests, mean unadjusted values did not differ between cohorts. Exenatide BID patients were more likely than liraglutide QD patients to continue pre-index glucose-lowering medications (67.1% vs 60.3%, p=0.027) or to start concomitant glucose-lowering medications at index (32.2% vs 25.0%, p=0.013); exenatide BID patients were less likely to augment treatment with another drug post-index (15.8% vs 22.5%, p=0.027). LIMITATIONS: Results may not be generalizable. Lab measures for clinical outcomes were available only for a sub-set of patients. CONCLUSIONS: Results suggested that some differences exist between patients initiating exenatide BID or liraglutide QD, with respect to prescribing physician specialty and pre- and post-index treatment patterns. Both GLP-1 receptor agonists showed comparable post-index HbA1c values in a sub-set of patients.

Annual costs of tumor necrosis factor inhibitors using real-world data in a commercially insured population in the United States.

OBJECTIVE: To calculate annual cost per treated patient of tumor necrosis factor (TNF) inhibitors etanercept, adalimumab, and infliximab for common approved indications, based on actual TNF-inhibitor use in clinical practice. METHODS: Adults with ≥1 claim for etanercept, adalimumab, or infliximab between January 2005 and March 2009 were identified from the IMS LifeLink™ Health Plan Claims Database. Patients new to therapy or continuing therapy (i.e., a prior claim for a TNF-inhibitor) were analyzed separately. Included patients had been enrolled from 180 days before the first TNF-inhibitor claim (index date) through 360 days after the index date and had a diagnosis during the pre-index period for rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis. Patients with Crohn's disease, ulcerative colitis, or juvenile idiopathic arthritis were excluded. Annual costs were calculated using wholesale acquisition costs for the TNF-inhibitor and Medicare Physician Fee Schedule for drug administration. Costs from restarting or switching TNF-inhibitor therapy during the first year were included. RESULTS: A total of 27,704 patients (11,528 new, 16,176 continuing) had claims for etanercept, adalimumab, or infliximab, most commonly (65%) for treatment of rheumatoid arthritis. The most commonly used agent was etanercept (14,777 patients; 53%), followed by adalimumab (6862 patients; 25%) and infliximab (6065 patients; 22%). Annual cost per treated patient was etanercept $14,873, adalimumab $17,766, and infliximab $21,256 across all indications. Annual cost per treated patient by disease was (etanercept/adalimumab/infliximab): rheumatoid arthritis ($14,314/$17,700/$20,390), psoriasis ($17,182/$17,682/$23,935), psoriatic arthritis ($15,030/$18,483/$24,974), and ankylosing spondylitis ($14,254/$16,925/$23,056). New and continuing patients showed similar results, with etanercept having the lowest costs. LIMITATIONS: This analysis is limited to three TNF-inhibitors and a US managed-care population. CONCLUSIONS: Based on this analysis of real-world use of TNF-inhibitors among patients in nationwide clinical practice settings, the annual TNF-inhibitor cost per treated patient was lowest for etanercept across all indications.