Treatment patterns, healthcare utilization, and costs of patients with treatment-resistant depression initiated on esketamine intranasal spray and covered by US commercial health plans.

AIMS: To describe real-world use of esketamine (ESK) intranasal spray and healthcare outcomes among patients with treatment-resistant depression (TRD) in the United States (US). METHODS: Adults with TRD initiated on ESK (index date) between 5 March 2019 (US approval date for TRD) and 31 October 2020 were sampled from IBM MarketScan Research Databases. TRD was defined as claims for ≥2 unique antidepressants during the same major depressive episode. Subgroups of the TRD cohort with comorbid cardiometabolic conditions, pain, anxiety disorder, and substance use disorder (SUD) were identified. Patients had ≥6 months of continuous health plan eligibility pre- and post-index. RESULTS: The TRD cohort comprised 269 patients; comorbidity subgroups included 123 (cardiometabolic), 144 (pain), 189 (anxiety disorder), and 58 (SUD) patients. Proportion of patients completing ≥8 ESK sessions (number of sessions in induction phase) was 61.3% in the TRD cohort and ranged from 60.2% (cardiometabolic subgroup) to 72.4% (SUD subgroup) in subgroups. Median frequency of induction sessions was every 5-8 days among the TRD cohort and subgroups. Mean mental health-related inpatient costs reduced from pre- to post-index periods in the TRD cohort (mean ± standard deviation [median] costs per-patient-per-6-months: $3,480 ± $13,328 [$0] pre-ESK initiation; $3,262 ± $16,666 [$0] post-ESK initiation; mean difference: -$218) and subgroups (largest decrease in cardiometabolic subgroup: $4,864 ± $14,271 [$0]; $2,792 ± $15,757 [$0]; -$2,072). Mean mental health-related emergency department (ED) costs decreased in the TRD cohort ($608 ± $2,525 [$0]; $269 ± $1,143 [$0]; -$339) and subgroups (largest decrease in the SUD subgroup: $1,403 ± $3,752 [$0]; $351 ± $868 [$0]; -$1,052). LIMITATIONS: This is a descriptive analysis; sample size for some comorbidity subgroups is small. CONCLUSIONS: The majority of patients completed ESK induction phase, and most dosing intervals were longer than the label recommendation. In this descriptive analysis, mental health-related inpatient and ED costs trended lower post-ESK initiation.

Characteristics of Real-world Commercially Insured Patients With Treatment-resistant Depression Initiated on Esketamine Nasal Spray or Conventional Therapies in the United States.

PURPOSE: This study aimed to characterize patients with treatment-resistant depression (TRD) initiating esketamine or conventional therapies. METHODS: Adults with major depressive disorder (MDD) were selected from the IBM MarketScan Databases. A claims-based algorithm identified patients with evidence of TRD, defined as initiation of a new antidepressant therapy after 2 different antidepressant trials of adequate dose and duration during the most recent major depressive episode. Patients receiving treatment on/after March 5, 2019 (esketamine approval date for TRD), were classified to the esketamine cohort if they newly initiated esketamine (index date) or to the TRD conventional therapies cohorts if they newly initiated electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), or pharmacologic therapies (index date was the therapy initiation date, prioritizing ECT, then TMS, then pharmacologic antidepressant therapies). Patient characteristics in the 6 months before therapy initiation were described. FINDINGS: The esketamine cohort included 246 patients (mean age, 46.5 years; 63.0% female), and the TRD conventional therapies cohorts included 104,164 patients (mean age, 46.9 years; 74.8% female; 0.4% initiated ECT, 1.2% initiated TMS). During the 6 months preindex, in the esketamine and TRD conventional therapies cohorts, 77.6% and 41.4% received psychotherapy and 82.9% and 34.2% had a psychiatrist visit, respectively. Most patients had outpatient care for MDD in the esketamine (91.9%) and TRD conventional therapies (63.6%) cohorts; 57.3% and 21.0% received care at specialized mental health care settings. MDD was classified as "severe" among 81.3% and 35.1% of patients in the esketamine and TRD conventional therapies cohorts . Preindex mental health-related (MHR) inpatient admissions and emergency department visits were identified in 12.2% and 16.3% of the esketamine cohort and in 8.2% and 10.3% of the TRD conventional therapies cohort. Before therapy initiation, 34.6% and 17.6% of the esketamine and TRD conventional therapies cohorts received ≥3 unique antidepressants. Suicidal ideation or behavior was observed in 8.5% and 3.6% of the esketamine and TRD conventional therapies cohorts pretherapy initiation. Mean monthly all-cause health care costs in the esketamine cohort were $2532 (58.2% MHR); in the TRD conventional therapies cohorts, costs were $1873 (32.4% MHR). IMPLICATIONS: Among patients with TRD, those initiating esketamine relative to conventional therapies displayed higher MDD severity, used more MHR inpatient/emergency department services and antidepressant treatments, and incurred higher health care costs 6 months pretherapy initiation. These findings suggest potential benefits of identifying and treating patients with TRD earlier with more effective treatments and should inform payers in consideration of esketamine coverage.

Characteristics and current standard of care among veterans with major depressive disorder in the United States: A real-world data analysis.

BACKGROUND: This study examined MDD treatment regimens received during the first observed and treated major depressive episode (MDE) among US veterans. METHODS: This retrospective study, conducted using the Veterans Health Administration (VHA) database, supplemented with Medicare Part A/B/D data, included adults with ≥1 MDD diagnosis (index date) between 10/1/2015-2/28/2017 and ≥1 line of therapy (LOT) within the first observed complete MDE. Patient baseline (6-month pre-index) characteristics and up to six LOTs received during the first observed and treated MDE were assessed. RESULTS: Of 40,240 veterans with MDD identified (mean age: 50.9 years, 83.9% male, 63.4% White, 88.6% non-Hispanic), hypertension (27.5%), hyperlipidemia (20.8%), and post-traumatic stress disorder (17.5%) were the most common baseline comorbidities. During the first observed and treated MDE, patients received a mean of 1.6 ± 1.0 LOTs, with 14.6% of patients receiving ≥3 LOTs. SSRI-monotherapy was the most commonly observed regimen in the first six LOTs, followed by SNRI-monotherapy in LOT 1 and antidepressants augmented by anticonvulsants in the remaining five LOTs. The antidepressant class of the previous LOT was commonly used in the subsequent LOT. SSRI-SSRI-SSRI was the most common LOT1-to-LOT3 sequencing pattern among patients receiving ≥3 LOTs. LIMITATIONS: The study findings are limited to data in the VHA database and may not be generalizable to the non-veteran US population. CONCLUSIONS: During the first observed and treated MDE, SSRI-monotherapy was the most common therapy in the first six LOTs. Cycling within SSRI class was the leading sequencing pattern of the first three LOTs among veterans who received ≥3 LOTs.

Health care resource use, short-term disability days, and costs associated with states of persistence on antidepressant lines of therapy.

AIMS: To compare health care resource utilization (HCRU), short-term disability days, and costs between states of persistence on antidepressant lines of therapy after evidence of treatment-resistant depression (TRD). METHODS: Patients with major depressive disorder (MDD) were identified in the IBM MarketScan Commercial and Medicare Supplemental Databases (01/01/2013-03/04/2019), Multi-State Medicaid Database (01/01/2013-12/31/2018), and Health Productivity Management Database (01/01/2015-12/31/2018). The index date was the date of the first evidence of TRD during the first observed major depressive episode. The follow-up period was divided into 45-day increments and categorized into persistence states: (1) evaluation (first 45 days after evidence of TRD); (2) persistence on the early line after evidence of TRD; (3) persistence on a late line; and (4) non-persistence. HCRU, short-term disability days, and costs were compared between persistence states using multivariate generalized estimating equations. RESULTS: Among 10,053 patients with TRD, the evaluation state was associated with higher likelihood of all-cause inpatient admissions (odds ratio [OR; 95% confidence interval (CI)] = 1.79 [1.49, 2.14]), emergency department visits (OR [95% CI] = 1.23 [1.12, 1.34]), and outpatient visits (OR [95% CI] = 3.83 [3.51, 4.18]; all p < .001) versus persistence on the early-line therapy. This resulted in $374 higher mean PPPM all-cause health care costs (95% CI = 265, 470; p < .001) during evaluation versus persistence on the early line therapy. The evaluation state was associated with 89% more short-term disability days (OR [95% CI] = 1.89 [1.49, 2.57] and $212 higher mean PPPM short-term disability costs (95% CI = 64, 259) relative to persistence on the early line (both p < .001). Moreover, during persistence on a later line, mean PPPM all-cause health care costs were $141 higher (95% CI = 13, 242; p = .028) relative to the early line. LIMITATIONS: Medication may have been dispensed but not actually taken. CONCLUSIONS: Higher costs during the first 45 days after evidence of the presence of TRD and during persistence on a late line relative to persistence on the early-line therapy suggest there are benefits to using more effective treatments earlier.

Prevalence of Pre-existing Conditions Relevant for Adverse Events and Potential Drug-Drug Interactions Associated with Augmentation Therapies Among Patients with Treatment-Resistant Depression.

INTRODUCTION: Pre-existing conditions relevant for adverse events (AE) and the potential for drug-drug interactions (DDIs) may limit safe pharmacotherapeutic augmentation options for patients with major depressive disorder (MDD). This concern may be heightened among patients with treatment-resistant depression (TRD), who often have comorbid medical disorders. METHODS: Adults with MDD and ≥ 1 antidepressant claim within the first observed major depressive episode were identified in the MarketScan® Databases. Those initiating a new regimen after two regimens at adequate dose and duration were considered to have TRD. The index date was defined at TRD onset or on a random antidepressant claim among patients with non-TRD MDD. Pre-existing conditions 12 months pre-index and potential DDIs 3 months pre/post-index associated with specific non-antidepressant augmentation therapies, including atypical antipsychotics (APs), buspirone, psychostimulants, anticonvulsants, thyroid hormone, and lithium were compared between 1:1 matched TRD and non-TRD MDD cohorts. RESULTS: Overall, 3414 patients with TRD and non-TRD MDD (mean age 39.7 years, 69% female) were matched. Relative to non-TRD MDD, patients with TRD had 33% higher likelihood of ≥ 1 pre-existing condition relevant for AEs listed in product labels of non-antidepressant augmentation therapies (p < 0.001). Patients with TRD vs. non-TRD MDD had 12.9 and 6.4 times higher likelihood of ≥ 2 and ≥ 3 DDIs, respectively, based on their medication regimen (all p < 0.001). CONCLUSION: Pre-existing conditions relevant for listed AEs and potential DDIs limit safe augmentation options in MDD, particularly among patients with TRD. Payer prior authorization policies requiring several augmentation therapy trials to access novel treatments may complicate clinical management of this population.

Quality of life in patients with type 2 diabetes after switching to insulin degludec: results from a cross-sectional survey.

PURPOSE: Five quality of life (QoL) domains are particularly important to patients with type 2 diabetes (T2D) using basal insulin-sense of physical well-being, sense of safety regarding hypoglycemia, sense of diabetes as burdensome, feelings of freedom and flexibility, and sleep quality. METHODS: An online survey assessed these QoL domains in adult patients with T2D in the USA who had switched from a previous basal insulin to insulin degludec (IDeg): modified versions of the World Health Organization (Five) Well-Being Index (WHO-5), Hypoglycemia Attitudes and Behavior Scale (HABS; confidence and anxiety subscales only), and Diabetes Distress Scale (DDS; emotional burden and regimen-related distress subscales only); three items assessing feelings of freedom and flexibility; and one item assessing sleep quality (hours of restful sleep). Patients rated each item for their previous basal insulin and currently while using IDeg. Correlations between sleep quality and the other QoL scales were also assessed. RESULTS: In total, 152 patients completed the survey and were included in the study sample. Patients reported significantly improved scores while using IDeg on all WHO-5, DDS, HABS, feelings of freedom and flexibility item scores, and total raw/mean subscale scores (P < 0.0001). Patients also reported a significantly greater number of hours of restful sleep [mean (SD) 6.6 (2.0) vs. 5.5 (1.8); P < 0.0001]. Better sleep quality statistically significantly correlated with improved QoL in all other domains assessed. CONCLUSIONS: Treatment with IDeg after switching from a previous basal insulin was associated with statistically significant improvements in all QoL domains assessed.

Preoperative intravenous meloxicam for moderate-to-severe pain in the immediate post-operative period: a Phase IIIb randomized clinical trial in 55 patients undergoing primary open or laparoscopic colorectal surgery with bowel resection and/or anastomosis.

Aim: Evaluate safety/efficacy of intravenous meloxicam in a colorectal enhanced recovery after surgery protocol. Methods: Adults undergoing primary open or laparoscopic colorectal surgery with bowel resection and/or anastomosis received meloxicam IV 30 mg (n = 27) or placebo (n = 28) once daily beginning 30 min before surgery. Results: Adverse events: meloxicam IV, 85%; placebo, 93%. Adverse events commonly associated with opioids: 41 versus 61% - including nausea (33 vs 50%), vomiting (19 vs 18%) and ileus (4 vs 18%). Wound healing satisfaction scores (physician-rated), clinical laboratory findings and vital signs were similar in both groups. No anastomotic leaks were reported. Opioid consumption, postoperative pain intensity, length of stay and times to first bowel sound, first flatus and first bowel movement were significantly lower with meloxicam IV versus placebo. Most subjects (>92%) were satisfied with postoperative pain medication. Conclusion: Meloxicam IV was generally well tolerated and associated with decreased opioid consumption, lower resource utilization and functional benefits. Clinical Trial Registration: NCT03323385 (ClinicalTrials.gov).

Pitfalls of Cost-Effectiveness Analysis in Practice: A TRD Case Example in the United States with Esketamine Versus Oral Antidepressants.

DISCLOSURES: The writing of this letter was supported by Janssen Scientific Affairs. The authors are employees of Janssen Scientific Affairs or Janssen Global Services (Johnson & Johnson).

Outcome Evaluation of a Subcutaneous Immunoglobulin Clinical Management Program.

OBJECTIVE: The aim of this study is to compare clinical and cost outcomes of patients undergoing subcutaneous immunoglobulin (SCIG) therapy who were managed by a clinical management program to the matched controls in the United States. METHODS: This was a retrospective cohort study using administrative claims data from the PharMetrics Plus™ (PMTX+) database. The patients from a high-touch SCIG clinical management program were matched to nonprogram patients in PMTX+ database using 1:4 propensity score matching without replacement. All patients were followed for 1 year during the study from September 1, 2011, to June 30, 2014, and both clinical and cost outcomes were compared between the two cohorts using the generalized estimating equation model. FINDINGS: The clinical outcomes were measured by infection- and infusion-related adverse events (AEs). Most of them were not significantly different (P > 0.05) between the intervention group and matched controls. Although the proportion of patients who had a mild less common AE was higher (4.4% vs. 0.0%;P = 0.04), it could be due to increased reporting among the intervention group. The annual adjusted mean total health-care costs of patients in the program (n = 45) were $20,868 lower compared to matched controls (n = 180), representing a 24% lower costs ($66,450 vs. $87,318;P = 0.009). CONCLUSION: This study may demonstrate that clinical management programs for SCIG may be associated with lower health-care costs and comparable infection and severe AE rates. The limitations of this study included a small sample size and a reliance on administrative claim data.

Effect of Weight Change on Economic Outcomes Among Persons with Type 2 Diabetes Mellitus in the United States: Beyond Glycemic Control.

BACKGROUND: Previous studies report weight loss to be associated with significantly lower total health care costs among patients with type 2 diabetes mellitus (T2DM). The effect of weight change on health care costs, independent of glycemic control and after controlling for time-varying covariates among T2DM patients, remains unknown. OBJECTIVE: To evaluate the effect of weight change, independent of glycemic control, on all-cause and T2DM-related health care resource utilization (HCRU) and costs among T2DM patients in the United States. METHODS: A retrospective cohort study was conducted using a linked data extract composed of IQVIA's RWI Data Adjudicated Claims-US and Ambulatory Electronic Medical Record data. Adults (aged ≥ 18 years) with T2DM receiving ≥ 1 oral antidiabetic drug (OAD) medication, glucagon-like peptide-1 receptor agonist (GLP-1RA), and/or short- or long-acting insulin between January 1, 2010, and December 31, 2014 were included (the date of the first observed medical claim with a diagnosis code or medication prescription claim was the index date). Baseline characteristics were evaluated in the 6-month pre-index period. Weight loss (3%, 5%, or 7% from baseline) was evaluated over two 6-month periods (months 1-6 and 7-12) following the index date. Covariates included time-varying weight, hemoglobin A1c (A1c), costs, and HCRU within each 6-month period. Outcomes of interest (all-cause and T2DM-related HCRU and costs) were evaluated in the 6-month (months 13-18) and 12-month (months 13-24) periods following the initial 1- to 6-month and 7- to 12-month post-index periods. Structural nested mean models were used to evaluate the effect of weight change on these outcomes, independent of glycemic control. RESULTS: 1,407 patients were included (mean age = 55 years; 55% male), with a mean baseline weight of 102.2 kg (median = 99.7 kg) and a mean baseline A1c of 7.4% (median = 6.9%). In adjusted analysis, weight loss was associated with significantly lower all-cause and T2DM-related annual total health care costs. Compared with those showing no weight change, a 3%, 5%, and 7% weight loss resulted in approximately $500, $800, and $1,100 in savings, respectively, in all-cause annual total health care costs per patient in the year following the weight loss. Similarly, compared with those with no weight change, a 3%, 5%, and 7% weight loss resulted in approximately $200, $300, and $400 in savings, respectively, in T2DM-related annual total health care costs per patient in the following year. Even greater savings (up to ~$2,000 and ~$800 in all-cause and T2DM-related annual costs per patient, respectively) were experienced by those who lost weight compared with those who gained weight. CONCLUSIONS: After accounting for glycemic control, this study found that weight loss was associated with additional significant reductions in all-cause and T2DM-related annual total health care costs. Understanding the role of weight loss in T2DM may provide useful evidence for decision makers as they evaluate therapy options for T2DM. DISCLOSURES: This study was funded by Novo Nordisk. Dang-Tan, Smolarz, and Iyer are employees of Novo Nordisk. Karkare and DeKoven (employees of IQVIA) and Fridman (employed by AMF Consulting) were contracted by Novo Nordisk to conduct this study. Fridman also reports personal fees from Shire, GSK, and CSL Behring, outside of the submitted work. Lu, an employee of IQVIA, accessed the database and conducted the statistical analysis for this study.

Clinical and economic outcomes of a "high-touch" clinical management program for intravenous immunoglobulin therapy.

OBJECTIVE: To compare clinical and economic outcomes of patients who received intravenous immunoglobulin (IVIG) therapies and were managed by a clinical management program vs the outcomes of matched controls using administrative claim data. METHODS: This retrospective cohort study used the PharMetrics Plus™ claim database between September 1, 2011 and June 30, 2014. Patients in the intervention group were from a "high-touch" IVIG clinical management program administered by a home infusion specialty pharmacy. A greedy propensity score matching algorithm was used to identify a control group from non-program patients. Generalized estimating equation models were employed to evaluate differences between cohorts who were followed for 1 year. RESULTS: Clinical outcomes were measured as infections and infusion-related adverse events. The proportion of patients who had serious bacterial infections was significantly lower (4.13% vs 7.75%, P=0.049) in the intervention group (n=242) compared to the control group (n=968). Other clinical outcomes assessed were not different between cohorts (P>0.050). The economic outcomes were measured as healthcare costs. The annual adjusted mean total health care costs of patients in the program were $26,522 lower compared to matched controls, representing a 20% lower cost ($109,476 vs $135,998, P=0.002). A major contribution to this difference ($17,269) was IVIG-related total outpatient cost (intervention vs control groups: $64,080 vs $81,349, P=0.001). CONCLUSION: The patients in this high-touch IVIG clinical management program appeared to have comparable infections or adverse event rates and significantly lower total health costs compared to their matched controls.

Impact of a structured patient support program on adherence and persistence in basal insulin therapy for type 2 diabetes.

OBJECTIVE: Treatment adherence and persistence are essential to achieving therapeutic goals in diabetes and may be improved by patient support programs (PSPs). The COACH Program was launched in 2015 with the goal of supporting patients with diabetes who are prescribed insulin glargine 300 U/mL (Gla-300). The study objective was to assess the program's impact on persistence and adherence with therapy among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A retrospective 12-month analysis was conducted to compare treatment adherence and persistence in patients treated with Gla-300 who actively participated in the COACH PSP versus those who did not enroll using COACH engagement and claims data for the identification period from February 1, 2016 to July 31, 2016. COACH (n=544) and non-COACH (n=544) participants were matched on selected baseline characteristics. RESULTS: COACH participants were more likely to be adherent to (68.0% vs 61.4%, p= 0.0201; OR: 1.81, p=0.0002) and persistent (48.5% vs 42.1%, p= 0.0309; discontinuation HR: 0.60, p<0.0001) with Gla-300 than non-COACH patients during the 12-month follow-up after controlling for clinical confounders. Additionally, both insulin-naive and basal insulin switcher COACH participants, respectively, were more likely to be adherent (OR: 2.25, p=0.0082 and OR: 1.662, p=0.0364) and persistent (discontinuation HR: 0.53, p=0.0054 and HR: 0.67, p=0.0492) than non-COACH patients. Finally, COACH participants with greater level of engagement showed better persistence. CONCLUSION: These data demonstrate that participation and engagement with COACH PSPs are associated with improved persistence and adherence to Gla-300 among patients with type 2 diabetes.

"Real-World" Comparison of Prasugrel With Ticagrelor in Patients With Acute Coronary Syndrome Treated With Percutaneous Coronary Intervention in the United States.

OBJECTIVES: The 30-day clinical outcomes with prasugrel or ticagrelor were compared using a US payer database in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). BACKGROUND: Prasugrel and ticagrelor demonstrated superior efficacy with increased non-coronary artery bypass graft major bleeding compared with clopidogrel in randomized clinical trials. No direct randomized or observational studies have compared clinical outcomes between prasugrel and ticagrelor. METHODS: Patients hospitalized for ACS-PCI between August 1, 2011 and April 30, 2013 and prescribed prasugrel or ticagrelor were selected. Drug treatment cohorts were propensity matched based upon demographic and clinical characteristics. The primary objective compared 30-day net adverse clinical events (NACE) in prasugrel- and ticagrelor-treated patients using a prespecified 20% noninferiority margin. Secondary objectives included comparisons of major adverse cardiovascular events (MACE) and major bleeding. RESULTS: Data were available for 16,098 patients (prasugrel, n = 13,134; ticagrelor, n = 2,964). In unmatched cohorts, prasugrel-treated patients were younger with fewer comorbidities than ticagrelor-treated patients, and 30-day NACE rates were 5.6 and 9.3%, respectively (P < 0.001). Following propensity matching, NACE was noninferior (P < 0.001) and 22% lower in prasugrel-treated than in ticagrelor-treated patients (RR, 0.78; 95% CI, 0.64-0.94). A 30-day adjusted MACE (RR, 0.80; 95% CI, 0.64-0.98) and major bleeding (RR, 0.65; 95% CI, 0.45-0.95) were also lower in prasugrel-treated patients compared with ticagrelor-treated patients. CONCLUSIONS: In this "real-world," retrospective, observational study, physicians appear to preferentially use prasugrel in younger patients with lower risk of bleeding or comorbidities compared with ticagrelor. Following adjustment, clinical outcomes associated with prasugrel use appear as good, if not better, than those associated with ticagrelor in ACS-PCI patients. © 2015 Wiley Periodicals, Inc.

Comparison of healthcare resource utilization and costs in patients hospitalized for acute coronary syndrome managed with percutaneous coronary intervention and receiving prasugrel or ticagrelor.

OBJECTIVE: To compare healthcare resource utilization (HCRU) and healthcare costs in patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) and treated with prasugrel or ticagrelor. METHODS: Hospital charge master data were used to identify ACS-PCI patients aged ≥ 18 years with ≥ 1 in-hospital claim for prasugrel or ticagrelor between August 1, 2011-April 30, 2013. Treatment groups were propensity matched for baseline and index hospitalization characteristics. HCRU and costs were assessed through 90-days post-discharge. Costs were determined based on hospital-specific cost-to-charge ratios and adjusted to 2013 US dollars. RESULTS: Before matching, ticagrelor patients were older, more-often female, and had increased cardiovascular (CV) and bleeding risks compared with prasugrel patients. Propensity-matched length of index hospital stay (4.7 vs 4.9 days, p = 0.23) and risk for all-cause [30-day: relative risk (RR) = 0.86; 95% CI = 0.73-1.0; 90-day: RR = 0.90; 95% CI = 0.80-1.0, and CV-related (30-day: RR = 0.77; 95% CI = 0.59-1.0; 90-day: RR = 0.89; 95% CI = 0.73-1.1) re-hospitalizations did not significantly differ between prasugrel and ticagrelor, respectively. Compared to ticagrelor, the propensity-matched risk of re-hospitalization for myocardial infarction (MI) (30-day: RR = 0.39; 95% CI = 0.21-0.75; 90-day: RR = 0.53; 95% CI = 0.34-0.81) and an outpatient medical encounter for dyspnea (30-day: RR = 0.49; 95% CI = 0.33-0.74; 90-day: RR = 0.60; 95% CI = 0.46-0.80) were significantly lower for prasugrel patients, with no significant differences in bleeding encounters between groups (30-day: RR = 0.87; 95% CI = 0.54-1.40; 90-day: RR = 1.0; 95% CI = 0.71-1.50). Matched total healthcare costs were not significantly different between groups during the index hospitalization ($36,011 vs $37,247, p = 0.21), 30-days post-discharge ($2007 vs $2522, p = 0.48), 90-days post-discharge ($4564 vs $5242, p = 0.49), and aggregate of the index hospitalization through 90-day follow-up ($40,576 vs $42,494, p = 0.09) timeframes. CONCLUSIONS: Re-hospitalization for MI and outpatient encounters for dyspnea were lower in prasugrel treated than in ticagrelor treated ACS-PCI patients up to 90-days post-index hospitalization discharge, with no difference in bleeding encounters or healthcare costs between the two populations. This data supports the utility of prasugrel in routine clinical practice. These findings should be considered within limitations of observational research.

Persistence with and adherence to fingolimod compared with other disease-modifying therapies for the treatment of multiple sclerosis: a retrospective US claims database analysis.

OBJECTIVE: Achieving therapeutic goals in multiple sclerosis (MS) requires strict adherence to treatment schedules. This retrospective study analyzed persistence with, and adherence to, fingolimod compared with injectable/infusible disease-modifying therapies (DMTs) in patients with MS. METHODS: Patients in the PharMetrics Plus™ US administrative claims database with at least one prescription for, or administration of, fingolimod, glatiramer acetate (GA), interferon (IFN), or natalizumab (index DMT) between October 1, 2010 and September 30, 2011 were included. Patients were naïve to index DMT (no claim in the previous 360 days) and had an MS diagnosis code within 360 days of the first index DMT prescription. Outcomes were persistence, risk of discontinuing index DMT (evaluated by a Cox proportional hazards model), adherence (measured using the medication possession ratio [MPR] and proportion of days covered [PDC] in patients with at least two index DMT prescriptions), and the risk of being non-adherent (MPR <80% and PDC <80%, assessed using a logistic regression model). RESULTS: The study included 3750 patients (fingolimod, n = 889; GA, n = 1233; any IFN, n = 1341; natalizumab, n = 287). Discontinuation rates (fingolimod, 27.9%; GA, 39.5%; IFN, 43.7%; natalizumab, 39.5%; all p < 0.001) and risk of discontinuation were significantly higher (hazard ratios vs fingolimod [95% confidence interval]: GA, 1.75 [1.49-2.07]; IFN, 2.01 [1.71-2.37]; natalizumab, 1.53 [1.22-1.91]) for patients receiving other DMTs compared with fingolimod. The risk of being non-adherent was also lower for patients in the fingolimod cohort than the other treatment cohorts, irrespective of whether non-adherence was defined as MPR <80% (p < 0.05 for all) or PDC <80% (p < 0.05 for GA and IFN). LIMITATIONS: As with all studies assessing real-world treatment patterns it is unclear if medications were used as prescribed. CONCLUSIONS: In a real-world setting, persistence with, and adherence to, oral fingolimod was higher than for injectable and infusible DMTs.

Relapse rates in patients with multiple sclerosis switching from interferon to fingolimod or glatiramer acetate: a US claims database study.

BACKGROUND: Approximately one-third of patients with multiple sclerosis (MS) are unresponsive to, or intolerant of, interferon (IFN) therapy, prompting a switch to other disease-modifying therapies. Clinical outcomes of switching therapy are unknown. This retrospective study assessed differences in relapse rates among patients with MS switching from IFN to fingolimod or glatiramer acetate (GA) in a real-world setting. METHODS: US administrative claims data from the PharMetrics Plus™ database were used to identify patients with MS who switched from IFN to fingolimod or GA between October 1, 2010 and March 31, 2012. Patients were matched 1∶1 using propensity scores within strata (number of pre-index relapses) on demographic (e.g. age and gender) and disease (e.g. timing of pre-index relapse, comorbidities and symptoms) characteristics. A claims-based algorithm was used to identify relapses while patients were persistent with therapy over 360 days post-switch. Differences in both the probability of experiencing a relapse and the annualized relapse rate (ARR) while persistent with therapy were assessed. RESULTS: The matched sample population contained 264 patients (n = 132 in each cohort). Before switching, 33.3% of patients in both cohorts had experienced at least one relapse. During the post-index persistence period, the proportion of patients with at least one relapse was lower in the fingolimod cohort (12.9%) than in the GA cohort (25.0%), and ARRs were lower with fingolimod (0.19) than with GA (0.51). Patients treated with fingolimod had a 59% lower probability of relapse (odds ratio, 0.41; 95% confidence interval [CI], 0.21-0.80; p = 0.0091) and 62% fewer relapses per year (rate ratio, 0.38; 95% CI, 0.21-0.68; p = 0.0013) compared with those treated with GA. CONCLUSIONS: In a real-world setting, patients with MS who switched from IFNs to fingolimod were significantly less likely to experience relapses than those who switched to GA.

Comparative effectiveness of fingolimod versus interferons or glatiramer acetate for relapse rates in multiple sclerosis: a retrospective US claims database analysis.

OBJECTIVE: Disease-modifying therapies, such as fingolimod, interferon (IFN) and glatiramer acetate (GA), have differing effects on relapse rates in patients with multiple sclerosis (MS), but little is known about the real-world differences in relapse rates with these treatments. This retrospective study assessed relapse rates in patients with active MS initiating fingolimod, IFN or GA therapy in a real-world setting. METHODS: Using administrative claims data from the US PharMetrics Plus database, we identified previously treated and untreated patients with MS who initiated fingolimod, IFN or GA treatment between 1 October 2010 and 31 March 2011 and had experienced a relapse in the previous year. A claims-based algorithm was used to identify relapses over the persistence period in patients with 540 days of post-index continuous enrolment. A logistic regression model assessed the probability of having at least one relapse and a generalized linear model estimated differences in annualized relapse rates (ARRs). RESULTS: The study enrolled 525 patients (fingolimod, n = 128; combined IFN/GA cohort, n = 397) of the 31,041 initially identified. Similar findings for fingolimod and IFN/GA were observed for the unadjusted proportion of patients experiencing relapses (31.3% vs. 34.0%, respectively; p = 0.5653) and ARRs (0.50 vs. 0.55, respectively) while persistent to treatment. After adjusting for baseline differences, fingolimod was associated with a 52% reduction in the probability of having a relapse (odds ratio, 0.48; 95% confidence interval [CI], 0.28-0.84; p = 0.0097) and a 50% reduction in ARR (rate ratio, 0.50; 95% CI, 0.34-0.75; p = 0.0006) compared with IFN/GA. LIMITATIONS: Identification of relapses is based on the claims in the database rather than on a clinical assessment. CONCLUSIONS: In a real-world setting, fingolimod was shown to be associated with significantly lower relapse rates than IFN/GA in patients with MS who had a history of relapses.

Improving the efficiency and effectiveness of pragmatic clinical trials in older adults in the United States.

Pragmatic clinical trials (PCTs) seek to improve the generalizability and increase the statistical power of traditional explanatory trials. They are a major tenet of comparative effectiveness research. While a powerful study design, PCTs have been limited by high cost, modest efficiency, and limited ability to fill relevant evidence gaps. Based on an American Reinvestment and Recovery Act (ARRA) supported meeting of national stakeholders, we propose several innovations and future research that could improve the efficiency and effectiveness of such studies focused in the U.S. Innovations discussed include optimizing the use of community based practices through partnership with Practice Based Research Networks (PBRNs), using information technology to simplify PCT subject recruitment, consent and randomization processes, and utilizing linkages to large administrative databases, such as Medicare, as a mechanism to capture outcomes and other important PCT variables with lower subject and research team burden. Testing and adaptation of such innovations to PCT are anticipated to improve the public health value of these increasingly important studies.

Incorporating stakeholder perspectives in developing a translation table framework for comparative effectiveness research.

This project used a stakeholder-driven process to understand the factors that drive the selection of study designs for comparative effectiveness research (CER). The project assembled a diverse stakeholder committee to explore the basis of a translation framework and gathered input through surveys, interviews and an in-person meeting. Stakeholders recommended different study designs for the CER topic areas and identified different outcomes as the most important outcomes to study in each area. During the discussions, stakeholders described a variety of factors that influenced their study design recommendations. The stakeholder activities resulted in the identification of several key themes, including the need to have a highly specific detailed research question before discussing appropriate designs and the need to use multiple studies, potentially of different designs, to address the CER topic areas. The insights and themes from this project may inform efforts to develop a translation table.

Prevalence and predictors of antidepressant prescribing in nursing home residents in the United States.

BACKGROUND: Late-life depression is a common psychiatric disorder associated with increased morbidity and mortality. Depression is often under-detected and undertreated in elderly nursing home residents. OBJECTIVES: The aim of this study was to examine the prevalence of antidepressant drug use and to identify the factors associated with its use among elderly nursing home residents. METHODS: The study involved the analysis of a nationally representative sample of prescription and resident files from the 2004 National Nursing Home Survey (NNHS). The study sample included all elderly nursing home residents ≥65 years of age. The analysis focused on prescribing from any antidepressant class, including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), serotonin modulators, serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), and others. Descriptive weighted analysis was performed to examine antidepressant use prevalence patterns in elderly nursing home residents. Multiple logistic regression analysis within the conceptual framework of Anderson's behavioral model was used to examine the predisposing, enabling, and need characteristics associated with antidepressant use. RESULTS: According to the 2004 NNHS, overall prevalence of antidepressant use among elderly nursing home residents was 46.22% (95% CI, 45.16-47.27). Most antidepressant users were ≥85 years of age (49.7%), female (75.7%), non-Hispanic (96.4%), and white (91.1%). The most prescribed class of antidepressants was SSRIs (31.09%; 95% CI, 30.12-32.07), followed by serotonin modulators (4.65%; 95% CI, 4.22-5.09), SNRIs (2.78%; 95% CI, 2.45-3.12), TCAs (2.34%; 95% CI, 2.03-2.65), and MAOIs (0.01%; 95% CI, 0.00-0.03). Citalopram (12.92%; 95% CI, 12.21-13.63) was the most prescribed individual antidepressant, followed by mirtazapine (10.19%; 95% CI, 9.55-10.84). Among the predisposing characteristics, age, race, and marital status were significantly associated with antidepressant use. The odds of receiving an antidepressant were lower for those aged ≥85 years and those who were unmarried elderly residents, when compared with their counterparts; whites were more likely to receive an antidepressant than nonwhites. Enabling factors such as Medicaid and bed capacity significantly predicted antidepressant use. Having Medicaid was positively associated with antidepressant prescription, whereas an increase in the total number of beds decreased the probability of an antidepressant prescription. Among need characteristics, the likelihood of antidepressant prescription use decreased with increased dependence in decision-making ability and out-of-bed mobility. The presence of depressed mood indicators and a history of falls/fractures increased the likelihood of antidepressant prescription use. The odds of receiving an antidepressant increased with diagnosis of depression but decreased with diagnosis of anxiety. CONCLUSION: Nearly half of elderly nursing home residents received antidepressants. In addition to need factors, predisposing and enabling factors played an important role in influencing the use of antidepressants in elderly nursing home residents.