Multi-Stakeholder Qualitative Interviews to Inform Measurement of Patient Reported Outcomes After CAR-T.

Toxicities after chimeric antigen receptor T cell (CAR-T) therapy are well known, yet the patient experience during and after CAR-T therapy has not been well described outside of the trial setting. We explored the patient experience after CAR-T therapy to inform the patient-reported outcomes (PRO) measurement approach for the Center for International Blood and Marrow Transplant Research (CIBMTR). We recruited (1) adult patients diagnosed with a hematologic malignancy 14 days to 6 months after receiving a commercial CAR T cell product who had agreed to be contacted by the CIBMTR, (2) caregivers of those patients, and (3) clinical experts in CAR-T therapy. Telephone interviews were conducted following a semistructured guide that included open-ended questions about symptoms and functioning. We conducted a systematic content analysis of each transcript using prespecified codes representing common domains of health, as well as open coding for emergent themes. Forty patients at 29 centers, 15 of their caregivers, and 15 experts from 9 centers participated, representing diversity with respect to age, sex, race/ethnicity, and years in practice (experts). Patients, caregivers, and experts shared largely consistent impressions of the patient experience after CAR-T therapy. Commonly described themes included anxiety, cognitive dysfunction, depression, fatigue, pain, impaired physical function, gastrointestinal symptoms, sexual dysfunction, sleep difficulties, need for support, financial impact, hospitalization, communication with healthcare providers, and the COVID-19 pandemic. Limitations in patients' ability to participate in social roles and activities was the most prevalent theme, found in nearly all interviews. In the setting of CAR-T therapy, a multidimensional approach to PRO measurement is needed that includes physical, mental, and social health, as well as the financial impact of this novel treatment. High-quality existing PRO tools are available to measure these concepts. Results will inform the CIBMTR measurement of PROs after CAR-T therapy and may be applicable to other CAR-T studies that aim to represent patient experiences.

Healthcare resource use and reimbursement amount by site of care in patients with diffuse large B-cell lymphoma receiving chimeric antigen receptor T-cell (CAR-T) therapy - a retrospective cohort study using CMS 100% Medicare claims database.

Chimeric antigen receptor T-cell (CAR-T) infusion settings may impact healthcare resource use (HRU) and reimbursement amounts. Adults with diffuse large B-cell lymphoma receiving CAR-T therapy were identified from the Centers for Medicare & Medicaid Services (CMS) 100% fee-for-service Medicare database and stratified into inpatient (IP; n = 380) and outpatient (OP; n = 50) cohorts based on CAR-T infusion setting. During the first month post-infusion, OP cohort had significantly fewer IP visits, IP days, intensive care unit (ICU) stays, ICU days, and significantly more OP, emergency room (ER) visits, than IP cohort. In subsequent months, HRU became comparable between cohorts. Medicare reimbursement amounts during the first month post-infusion were nominally higher in the OP vs. IP cohort and comparable in subsequent months. The reimbursement amounts did not reflect the reduced HRU with OP infusions, potentially due to differences in Medicare payment policies for OP vs. IP services.

A Retrospective Cohort Study of Treatment Outcomes of Adult Patients With Relapsed or Refractory Follicular Lymphoma (ReCORD-FL).

This study (ReCORD-FL) sought to construct a historical control cohort to augment single-arm trials in relapsed/refractory follicular lymphoma (r/r FL). A retrospective study in 10 centers across North America and Europe was conducted. Adults with grade 1-3A FL were required to be r/r after ≥2 therapy lines including an anti-CD20 and an alkylator. After first becoming r/r, patients were required to initiate ≥1 additional therapy line, which defined the study index date. Endpoints were observed from start of each therapy line (including index line) until death, last follow-up, or December 31, 2020. Endpoints were complete response (CR) rate, overall response rate (ORR), time to next treatment or death (TNT-D), event-free survival (EFS), and overall survival (OS). One hundred eighty-seven patients were identified. Most patients' (80.2%) index therapy occurred in third line (3L) (range, 3L-6L). Median follow-up from FL diagnosis was 9 years (range, 1-21 years). CR and ORR to the index therapy were 39.0% and 70.6%, respectively. Median (95% confidence interval) EFS from index was 14.6 (11.0-18.0) months; median OS from index was 10.6 years. Outcomes worsened across successive treatment lines and for patients who were double refractory (r/r to both an anti-CD20 monoclonal antibody and an alkylator) or POD24 (progressed ≤24 months after front-line anti-CD20) at index. Findings demonstrate the unmet need of FL patients with multiply relapsed, double refractory, or POD24 disease. Based on robustness of the historical data collected and comparability with a previous study (SCHOLAR-5), ReCORD-FL presents a valuable source of control data for comparative studies in r/r FL.

Real-world healthcare resource utilization and costs associated with tisagenlecleucel and axicabtagene ciloleucel among patients with diffuse large B-cell lymphoma: an analysis of hospital data in the United States.

This study compared the real-world healthcare resource utilization (HRU), costs, adverse events (AEs), and AE treatments associated with the chimeric antigen receptor T-cell (CAR-T) therapies, tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel), for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). Adults with DLBCL who received tisa-cel or axi-cel were identified in the Premier Healthcare Database (2017-2020). Non-CAR-T costs, HRU, and AE rates during the infusion and follow-up periods were compared between the tisa-cel and axi-cel cohorts. Of 119 patients, 33 received tisa-cel (86% as inpatient infusion) and 86 received axi-cel (100% inpatient). Tisa-cel was associated with significantly shorter mean inpatient length of stay than axi-cel during infusion (11.3 vs. 18.3 days) and follow-up ([monthly] 3.9 vs. 6.9 days). Non-CAR-T costs were significantly lower for tisa-cel compared with axi-cel during infusion ($27594.8 vs. $51378.3) and follow-up ([monthly] $28777.3 vs. $46575.7; both p< .05). Rates of AEs and AE treatments were similar.

Comparative efficacy of tisagenlecleucel and lisocabtagene maraleucel among adults with relapsed/refractory large B-cell lymphomas: an indirect treatment comparison.

This study compared overall survival (OS), progression-free survival (PFS), complete response rate (CRR), and overall response rate (ORR) of tisagenlecleucel (tisa-cel) and lisocabtagene maraleucel (liso-cel) in relapsed or refractory large B-cell lymphomas (r/r LBCL). Using matching-adjusted indirect comparison (MAIC), individual patient-level data from JULIET (tisa-cel) were weighted to match the patient population in TRANSCEND (liso-cel). The main analysis compared infused JULIET patients (N = 106) with the TRANSCEND efficacy-evaluable set (EES) (N = 256 [infused]). After adjustment, OS, PFS, and the CRR were comparable between tisa-cel and liso-cel EES patients. The estimated adjusted 2-year OS, 2-year PFS, ORR, and CRR were 45.6, 38.2, 62.9, and 47.7%, respectively, for tisa-cel vs. 43.8, 42.1, 72.7, and 53.1% for liso-cel. A scenario analysis compared JULIET patients to the TRANSCEND primary analysis set (PAS) (N = 133). ORR was significantly higher in the TRANSCEND PAS compared with matched JULIET patients, but no significant differences in CRR were observed.

Cost-Effectiveness Analysis of Tisagenlecleucel for the Treatment of Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma in the United States.

PURPOSE: To assess the cost-effectiveness and cost-effective price of tisagenlecleucel, a novel, effective chimeric antigen receptor T-cell therapy, versus salvage chemotherapy (SC) for the treatment of relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) using a willingness-to-pay (WTP) threshold of $150,000 per quality-adjusted life year (QALY) gained from a US third-party payer's perspective. METHODS: A three-state (progression-free survival, progressive disease, and death), responder-based partitioned survival model with a lifetime horizon and 3% annual discount rate was developed. Overall survival (OS) and progression-free survival of tisagenlecleucel were estimated separately for patients with and without an overall response (OR), using data from JULIET ( Study of Efficacy and Safety of CTL019 in Adult DLBCL Patients). OS of SC was informed by SCHOLAR-1 (Retrospective Non-Hodgkin Lymphoma Research). Mixture cure models were used to inform the survival of tisagenlecleucel responders, supported by JULIET. The median OS was 11.1 months in all tisagenlecleucel-treated patients but not reached for responders; no progression or death occurred among responders since month 22 of treatment. For tisagenlecleucel nonresponders and SC, survival was based on standard parametric models until month 60and the survival of DLBCL long-term survivors thereafter. The model prediction validated well against the observed trial data. Costs and utilities were from the literature; utilities depended on health states and were used to estimate QALYs. Total costs, QALYs, and incremental cost per QALY gained were estimated. A cost-effective price range was estimated for all tisagenlecleucel-treated patients, OR responders, and complete response (CR) responders. Deterministic sensitivity and scenario analyses and a probabilistic sensitivity analysis were performed. All costs were reported in or inflated to 2020 US dollars. FINDINGS: Tisagenlecleucel was associated with 3.35 QALYs gained versus SC.,The estimated incremental costs per QALY gained versus SC were $78,652 using the wholesale acquisition cost of $373,000 for tisagenlecleucel. The estimated cost-effective price of tisagenlecleucel in all treated patients was $612,270 at the WTP threshold of $150,000. Tisagenlecleucel OR and CR responders had an increase of 7.82 and 9.34 QALYs versus SC, with cost-effective prices estimated at $1,281,456 and $1,551,974, respectively. Sensitivity analysis results supported the base case findings. IMPLICATIONS: Tisagenlecleucel is a cost-effective treatment versus SC for r/r DLBCL from the perspective of a US third-party payer. The estimated cost-effective prices ranged from $612,270 (all tisagenlecleucel-treated patients) to up to $1.5 million (patients achieving CR). Limitations include the use of single-arm trials due to data availability.

Health-Related Quality of Life Improvements in Moderate to Very Severe Chronic Obstructive Pulmonary Disease Patients on Nebulized Glycopyrrolate: Evidence from the GOLDEN Studies.

Background: Symptoms of chronic obstructive pulmonary disease (COPD) may diminish patients' health-related quality of life (HRQoL). We report effects of Longhala™ Magnair™ (glycopyrrolate) Inhalation Solution, a drug/device combination of the long-acting antimuscarinic glycopyrrolate administered using the eFlow® closed system (eFlow CS) nebulizer, on HRQoL from the Glycopyrrolate for Obstructive Lung Disease Via Electronic Nebulizer (GOLDEN) clinical studies. Methods: Data consisted of a pooled analysis of 2 phase 3, 12-week efficacy studies (GOLDEN-3 and -4) of glycopyrrolate/eFlow CS (25 or 50 mcg twice daily [BID]) versus placebo, and a 48-week, open-label safety study (GOLDEN-5) of glycopyrrolate/eFlow CS 50 mcg BID versus tiotropium 18 mcg once daily in patients with moderate to very severe COPD. Change from baseline in HRQoL was measured via the St George's Respiratory Questionnaire (SGRQ). Results are provided as mean changes in SGRQ Total score and as response analysis (≥4-point improvement [responder], no change, and ≥4-point worsening in Total score) using analysis of covariance or logistic regression, as applicable. Results: Atotal of 1293 patients were evaluated from GOLDEN-3 and -4 and 1086 from GOLDEN-5. Glycopyrrolate/eFlow CS significantly improved SGRQ Total and component scores. The percentage of SGRQ responders in pooled GOLDEN-3/4 was 46.8% for glycopyrrolate/eFlow CS 25 mcg, 41.7% for glycopyrrolate/eFlow CS 50 mcg, and 34.5% for placebo. SGRQ Total and component score improvements were similar between glycopyrrolate/eFlow CS and tiotropium in GOLDEN-5. Conclusions: The drug/device combination of glycopyrrolate/eFlow CS significantly improved HRQoL, as measured by the SGRQ, offering a potential maintenance treatment option in patients with moderate to very severe COPD. ClinicalTrials.gov: NCT02347761, NCT02347774, NCT02276222.

Treatment patterns for patients hospitalized with chronic obstructive pulmonary disease.

PURPOSE: Medication treatment patterns for chronic obstructive pulmonary disease (COPD) in inpatient settings were examined, as were the characteristics of patients treated with long-acting bronchodilators (LABDs) during hospitalization. METHODS: This retrospective study was conducted using inpatient administrative data from hospitals and medical centers nationwide. All patients discharged from the hospital from January 1, 2010, through December 31, 2012, who were at least 40 years of age, had a primary discharge diagnosis of COPD or a secondary diagnosis of COPD with a primary diagnosis of a respiratory condition, and treatment with a bronchodilator were included. Treatment patterns were described for inpatient use of medications, including short-acting ß-agonists (SABAs), long-acting ß-agonists (LABAs), short-acting muscarinic antagonists (SAMAs), and long-acting muscarinic antagonists. Logistic regression predicted characteristics of patients receiving LABDs. RESULTS: Only 5.5% of patients did not receive an SABA during the hospitalization: 71.7% received a single-product SABA, and 46.4% received an SABA-SAMA combination product, with some patients switching between or using SABA and SABA-SAMA combinations concurrently. Most patients (80.9%) received systemic corticosteroids, and nearly all (91.6%) were treated with antibiotics. Only 52.2% of patients received LABDs (39.3% LABAs). Patients treated with LABDs were more likely to have a primary COPD diagnosis, prior hospitalizations, spirometry use, and fewer comorbidities. CONCLUSION: A review of COPD-related inpatient admissions found that the majority of patients received the primary recommended treatments for acute exacerbations of COPD (SABAs, systemic corticosteroids, and antibiotics). However, maintenance therapy had been initiated for only about half of patients before discharge.

Long-term health-related quality-of-life and symptom response profiles with arformoterol in COPD: results from a 52-week trial.

Background: Symptom severity is the largest factor in determining subjective health in COPD. Symptoms (eg, chronic cough, dyspnea) are associated with decreased health-related quality of life (HRQoL). We evaluated the impact of arformoterol on HRQoL in COPD patients, measured by St George's Respiratory Questionnaire (SGRQ). Post hoc growth mixture model (GMM) analysis examined symptom response profiles. Methods: We examined data from a randomized, double-blind, parallel-group, 12-month safety trial of twice-daily nebulized arformoterol 15 µg (n=420) versus placebo (n=421). COPD severity was assessed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) status. GMM analysis identified previously unknown patient subgroups and examined the heterogeneity in response to SGRQ Symptoms scores. Results: SGRQ Total score improved by 4.24 points with arformoterol and 2.02 points with placebo (P=0.006). Significantly greater improvements occurred for arformoterol versus placebo in SGRQ Symptoms (6.34 vs 4.25, P=0.031) and Impacts (3.91 vs 0.97, P=0.001) scores, but not in Activity score (3.57 vs 1.75, P=0.057). GMM identified responders and nonresponders based on the SGRQ Symptoms score. End-of-study mean difference in SGRQ Symptoms scores between these latent classes was 20.7 points (P<0.001; 95% confidence interval: 17.6-23.9). Compared with nonresponders, responders were more likely current smokers (55.52% vs 44.02%, P=0.0021) and had more severe COPD (forced expiratory volume in 1 second [FEV1]: 1.16 vs 1.23 L, P=0.0419), more exacerbations (0.96 vs 0.69, P=0.0018), and worse mean SGRQ Total (59.81 vs 40.57, P<0.0001), Clinical COPD Questionnaire (3.29 vs 2.05, P<0.0001), and Modified Medical Research Council Dyspnea Scale (3.13 vs 2.75, P<0.0001) scores. Arformoterol-receiving responders exhibited significantly greater improvements in FEV1 (0.09 vs 0.008, P=0.03) and fewer hospitalizations (0.13 vs 0.24, P=0.02) than those receiving placebo. Conclusion: In this study, arformoterol treatment significantly improved HRQoL reflected by SGRQ. For the analysis performed on these data, arformoterol may be particularly effective in improving lung function and reducing hospitalizations among patients who are unable to quit smoking or present with more severe symptoms.

Readmission Risk in Chronic Obstructive Pulmonary Disease Patients: Comparative Study of Nebulized ß2-Agonists.

BACKGROUND: Bronchodilators are used for managing the symptoms of chronic obstructive pulmonary disease (COPD) and minimizing the risk of hospitalization and readmission. Hospital readmission is predictive of morbidity and mortality. OBJECTIVE: The study objective was to compare all-cause readmission risk in COPD patients receiving nebulized long-acting ß2-agonists (neb-LABAs) versus nebulized short-acting ß2-agonists (neb-SABA) following COPD-related hospitalization discharge. METHODS: This retrospective analysis utilized US-based pharmacy and medical claims records (2001-2011) to identify COPD patients aged ≥40 years receiving neb-LABA or neb-SABA treatment within 30 days following discharge from a COPD-related hospitalization. Patients had to be continuously enrolled in their health plan for ≥6 months before and after their first neb-LABA or neb-SABA prescription fill (index date), and adherent to the treatment for the first 3 months post-index date. To select patients with similar severity profiles, neb-LABA and neb-SABA patients were matched by baseline characteristics. Readmission risks were observed over the 6-month period following the index date and compared between neb-LABA and neb-SABA cohorts using the multiple variable Cox proportional hazards model. RESULTS: The analysis included 246 matched patients (neb-LABA = 123; neb-SABA = 123). The mean age was 67 years, and 54% were female. The average length of stay during index hospitalization was 4.4 days. After adjusting for potential confounders, the risk of readmission was 47% lower in the neb-LABA cohort than in the neb-SABA cohort (hazard ratio 0.53, 95% confidence interval 0.30-0.96; P = 0.0349). CONCLUSIONS: Patients receiving neb-LABAs had a significantly lower readmission risk within 6 months following a COPD-related hospitalization versus patients treated with neb-SABAs.

Health Status of Patients with Moderate to Severe COPD after Treatment with Nebulized Arformoterol Tartrate or Placebo for 1 Year.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is a progressive disease that impairs both objectively measured lung function and patient-reported health status. In a randomized clinical trial of patients with moderate to severe COPD, we compared changes in health status after adding arformoterol tartrate or placebo to patients' treatment regimens. METHODS: In this multicenter, double-blind trial, patients were randomized to receive nebulized arformoterol 15 µg BID (n = 420) or matched placebo (n = 421). Treatment with other COPD medications was permitted, except for long-acting ß2-agonists. Inclusion criteria were a forced expiratory volume in 1 second (FEV1) ≤65% of predicted, FEV1 >0.50 L, age ≥40 years, smoking history ≥15 pack-years, and a baseline breathlessness severity grade ≥2. The Clinical COPD Questionnaire (CCQ) was used to measure health status at randomization and at months 3, 6, and 12. CCQ scores range from 0 to 6, with higher scores indicating worse health status, and a decrease from baseline in total score by 0.4 point is considered clinically significant. Outcomes were analyzed by using mixed models for repeated measures. FINDINGS: At baseline, patients' mean age was 63.8 years; 42.9% of patients were female, and 51.4% were current smokers. The mean baseline CCQ total scores were 2.88 and 2.91 for the arformoterol and placebo groups, respectively. A total of 841 patients were randomized to receive either arformoterol (n = 420) or placebo (n = 421); among them, 211 (50.1%) who received placebo and 255 (60.7%) who received arformoterol completed the trial. Arformoterol-treated patients had greater mean improvement from baseline in CCQ total score (-0.18 vs 0.02; P = 0.001), symptoms (-0.21 vs 0.01; P = 0.002), functional state (-0.15 vs 0.02; P = 0.018), and mental state (-0.18 vs 0.02; P = 0.023) than patients receiving placebo. At study end, 38.3% of the arformoterol-treated patients and 30.8% of patients receiving placebo reported clinically significant improvements on the CCQ (P = 0.026). These improvements were only modestly correlated with improvements in FEV1 (r = -0.15; P < 0.01). IMPLICATIONS: In this 52-week trial, arformoterol-treated patients had greater improvements in health status than patients receiving placebo. Assessing health status along with lung function seems to provide additional information regarding the effectiveness of COPD maintenance treatments. ClinicalTrials.gov identifier: NCT00909779.

Exacerbations, health services utilization, and costs in commercially-insured COPD patients treated with nebulized long-acting ß2-agonists.

OBJECTIVE: This retrospective cohort study compared exacerbations, health services utilization, and costs among chronic obstructive pulmonary disease (COPD) patients who received nebulized arformoterol or nebulized formoterol therapy. METHODS: Using PharMetrics Plus health plan claims, 417 nebulized long-acting ß2-agonist (LABA) users meeting the study inclusion criteria were identified: had ≥2 fills of nebulized arformoterol or nebulized formoterol from January 1, 2009, to December 31, 2011, adhered to using their index drug ≥60% of the days during 1 year post-index, were ≥35 years old and continuously enrolled 180 days pre- and 1 year post-index, and did not use a nebulized LABA or have an asthma diagnosis during the pre-index period. Descriptive and multivariate analyses were performed. RESULTS: A total of 274 nebulized arformoterol users and 143 nebulized formoterol users were identified with comparable demographic characteristics. However, significant differences were observed between the two groups in some clinical characteristics at index including comorbidities and use of antibiotics. At 1 year post-index, a lower proportion of nebulized arformoterol users had ≥1 exacerbation compared to nebulized formoterol users (70.4% vs 80.4%; p = 0.028). Among patients with ≥1 hospital admission, COPD-related costs per inpatient stay were significantly lower for nebulized arformoterol users than nebulized formoterol users (median = $9542 vs $14,025; p = 0.009). After controlling for confounders, nebulized arformoterol users had 19% marginally lower risk of exacerbations than nebulized formoterol users (hazard ratio = 0.81, 95% confidence interval = 0.64-1.03; p < 0.084) and 14.4% marginally lower COPD-related total costs at 1 year post-index (p = 0.062), primarily related to fewer hospital readmissions (7.6% vs 12.2%) and lower average costs per readmission stay (median = $7392 vs $18 081; p = 0.006). CONCLUSIONS: This study suggests that the choice of nebulized LABA may influence COPD-related exacerbation occurrence and costs. Future studies with larger and more closely matched nebulized arformoterol and nebulized formoterol users are needed to confirm these findings.

Clinical and economic burden of breakthrough seizures.

PURPOSE: The purpose of this study was to measure health-care resource utilization and costs in treatment-adherent, previously seizure-free patients with epilepsy who were treated in the inpatient/emergency room (ER) setting for new-onset seizures, compared with matched controls. METHODS: The study used a retrospective case/control study design using administrative claims from the IMS PharMetrics™ database. We identified adult patients with epilepsy with 1+ ER visit/hospitalization with primary diagnosis of epilepsy between 1/1/2006 and 3/31/2011, preceded by 6months of seizure-free activity and antiepileptic drug (AED) treatment adherence (≥80% of days covered by any AED); the first observed seizure defined the "breakthrough" seizure/index event. Treatment-adherent patients with epilepsy without any ER/hospital admission for seizures served as controls: an outpatient epilepsy-related medical claim within the selection window was chosen at random as the index date. The following were continuous enrollment requirements for all patients: ≥12-month pre- and ≥6-month postindex. Each case matched 1:1 to a control using propensity score matching. All-cause and epilepsy-related (epilepsy/convulsion diagnosis, AED pharmacy) resource utilization and unadjusted and adjusted direct health-care costs (per person, 2012 US dollars (USD)) were assessed in a 6-month follow-up period. PRINCIPAL RESULTS: There were 5729 cases and 14,437 controls eligible. The final sample comprised 5279 matched case/control pairs. In unadjusted analyses, matched cases had significantly higher rates of all-cause hospitalization and ER visits compared to controls and significantly higher total all-cause direct health-care costs (median $12,714 vs. $5095, p<0.001) and total epilepsy-related costs among cases vs. controls (median $7293 vs. $1712, p<0.001), driven by higher inpatient costs. Among cases, costs increased with each subsequent seizure (driven by inpatient costs). Cases had 2.3 times higher adjusted all-cause costs and 8.1 times higher adjusted epilepsy-related costs than controls (both p<0.001). CONCLUSION: Inpatient/ER-treated breakthrough seizures occurred among 28.4% of our treatment-adherent study sample and were associated with significant incremental health-care utilization and costs, primarily driven by hospitalizations. Our findings suggest the need for better seizure control via optimal patient management and the use of effective AED therapy, which can potentially lower health-care costs.

Hospital readmissions following initiation of nebulized arformoterol tartrate or nebulized short-acting beta-agonists among inpatients treated for COPD.

BACKGROUND: Inpatient admissions for chronic obstructive pulmonary disease (COPD) represent a significant economic burden, accounting for over half of direct medical costs. Reducing 30-day readmissions could save health care resources while improving patient care. Recently, the Patient Protection and Affordable Care Act authorized reduced Medicare payments to hospitals with excess readmissions for acute myocardial infarction, heart failure, and pneumonia. Starting in October 2014, hospitals will also be penalized for excess COPD readmissions. This retrospective database study investigated whether use of arformoterol, a nebulized long-acting beta agonist, during an inpatient admission, had different 30-day all-cause readmission rates compared with treatment using nebulized short-acting beta agonists (SABAs, albuterol, or levalbuterol). METHODS: A US nationally representative hospital database was used to study adults aged ≥40 years, discharged between January, 2006 and March, 2010, and with a diagnosis of COPD. Patients receiving arformoterol on ≥80% of days following treatment initiation were compared with patients receiving a nebulized SABA during hospitalization. Arformoterol and nebulized SABA patients were matched (1:2) for age, sex, severity of inpatient admission, and primary/secondary COPD diagnosis. Logistic regression compared the odds of readmission while adjusting for age, sex, race, admission type, severity, primary/secondary diagnosis, other respiratory medication use, respiratory therapy use, oxygen use, hospital size, and teaching status. RESULTS: This retrospective study compared 812 arformoterol patients and 1,651 nebulized SABA patients who were discharged from their initial COPD hospital admission. An intensive care unit stay was more common among arformoterol patients (32.1% versus 18.4%, P<0.001), suggesting more severe symptoms during the initial admission. The observed readmission rate was significantly lower for arformoterol patients than for nebulized SABA patients (8.7% versus 11.9%, P=0.017), as were the adjusted odds of readmission (odds ratio 0.69, 95% confidence interval 0.51-0.92). CONCLUSION: All-cause 30-day readmission rates were significantly lower for arformoterol patients than nebulized SABA patients, both before and after adjusting for patient and hospital characteristics.

Risk of all-cause hospitalization in COPD patients initiating long-acting or short-acting beta agonist therapy.

OBJECTIVE: This retrospective claims study investigated the rates of all-cause hospitalization among chronic obstructive pulmonary disease (COPD) patients initiating treatment with short-acting beta agonists (SABA) or long-acting beta agonists (LABA). METHODS: Data from the 5% national sample of Medicare enrollees for 2006-2008 were used. Patients initiating COPD therapy were identified as those with no COPD therapy for ≥ 6-months prior to initiating SABA or LABA (administered via dry-powder inhalers, metered-dose inhalers, or nebulizer) treatment. All patients were continuously eligible for Medicare Parts A, B, and D for 18 months. Those enrolled in Medicare Advantage, who had asthma, or were < 65 years old were excluded. Differences in the rates of all-cause hospitalizations and time to all-cause hospitalization during the 6-month follow-up period were examined, while adjusting for demographics, clinical indicators, and health service use. RESULTS: Among 3017 COPD patients who met the inclusion criteria, 883 (30%) were LABA users and 2134 (70%) were SABA users. Overall, 21% of patients (16% [144/883] of LABA and 23% [492/2134] of SABA) had a hospitalization during the follow-up period. Mean time to hospitalization was 86 days for LABA vs 64 days for SABA patients (p < 0.05). The adjusted hazard ratio for hospitalization in a Cox proportional hazards model was 0.74 (95% CI = 0.62-0.90) for patients treated with LABA vs. SABA. LIMITATIONS: The analysis was adjusted for multiple background characteristics, but important measures of severity in COPD, such as measures of lung functioning, were not available and may have differed between patients treated with LABA or SABA. CONCLUSIONS: The results of this analysis indicate COPD patients initiating LABA treatment had a longer time to all-cause hospitalization and a 26% lower risk of hospitalization during the 6-months follow-up period compared to those initiating SABA therapy.

The economic burden of pleural effusions in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors.

OBJECTIVE: Tyrosine kinase inhibitors (TKI), the standard of care for patients with chronic myeloid leukemia (CML) patients, may in some cases lead to the development of pleural effusion (PE). The purpose of this study is to compare healthcare resource utilization and costs associated with PE among CML patients treated with a TKI therapy. METHODS: Two large retrospective claims databases (1999-2009) were combined to identify adult CML patients who received ≥1 TKI prescription before the index date, which was defined as 30 days before the first PE diagnosis for patients with PE and a randomly selected date for PE-free patients. Patients were followed for 6 months after the index date. PE and PE-free patients were matched on a 1:1 ratio. PE-related resource utilization and costs (measured in 2009 US dollars) were estimated for PE patients. All-cause and CML-related resource utilization and costs were compared between PE and PE-free patients. Multivariate regression models were used to control for confounding factors. RESULTS: The study included 186 matched pairs. PE-free and PE patients were on average 65.4 and 63.6 years old and 39.8% and 48.9% were female, respectively. PE patients had a significantly higher number of inpatient (IP) days, IP admissions, outpatient (OP) visits and emergency room (ER) visits than PE-free patients (all p < 0.01). All-cause medical services costs were $88,526 and $30,434 for PE and PE-free patients, respectively. After adjusting for confounding factors, the PE-related total medical costs were $47,288 (p < 0.01), which was mostly accounted for by higher IP (difference: $34,123, p < 0.01) and OP (difference: $9563, p < 0.05) costs. PE patients also incurred higher CML-related medical costs compared to PE-free patients (difference: $39,599; p < 0.01). CONCLUSION: PE presents a substantial economic burden for CML patients treated with TKI.

Healthcare utilization and costs in patients beginning pharmacotherapy for generalized anxiety disorder: a retrospective cohort study.

BACKGROUND: Patterns of healthcare utilization and costs in patients beginning pharmacotherapy for generalized anxiety disorder (GAD) have not been well characterized. METHODS: Using a large US health insurance database, we identified all patients with evidence of GAD (ICD-9-CM diagnosis code 300.02) who initiated pharmacotherapy with medications commonly used to treat GAD (eg, selective serotonin reuptake inhibitors [SSRIs], venlafaxine, benzodiazepines) between 1/1/2003 and 12/31/2007. We examined healthcare utilization and costs over the 12-month periods preceding and following date of initial receipt of such therapy ("pretreatment" and "follow-up", respectively). Patients with incomplete data were excluded. RESULTS: A total of 10,275 patients met all study inclusion criteria. Forty-eight percent of patients received SSRIs; 34%, benzodiazepines; and 6%, venlafaxine. SSRIs and venlafaxine were about three times more likely to be used on a long-term basis (> 90 days) than benzodiazepines (p < 0.01). In general, levels of healthcare utilization were higher during follow-up than pretreatment. Mean (SD) total healthcare costs increased from $4812 ($10,006) during pretreatment to $7182 ($22,041) during follow-up (p < 0.01); costs of GAD-related pharmacotherapy during follow-up were $420 ($485). CONCLUSIONS: More than one-half of patients initiating pharmacotherapy for GAD receive either SSRIs or venlafaxine. Levels of healthcare utilization and costs are greater in the year following initiation of therapy than in the immediately preceding one.

Epidemiology, survival, and costs of localized gastrointestinal stromal tumors.

PURPOSE: The aim of this study is to examine the epidemiologic and economic burden in surgically resected localized gastrointestinal stromal tumor (GIST) patients versus age- and gender-matched controls. METHOD: Two data sources were used to conduct a series of complementary analyses. First, the Surveillance, Epidemiology, and End Results (SEER) cancer registry was used to identify diagnosed GIST patients from 1993 to 2002 and determine incidence, prevalence, and 3-year survival. Second, using the SEER-Medicare linked database, a matched case-control analysis was conducted to determine resource utilization, GIST recurrence, and costs. Because GIST recurrence is not explicitly defined in the database, patterns in resource use were used to identify probable recurrence. Kaplan-Meier Sample Average (KMSA) Estimator technique was used to estimate costs of GIST and recurrence. RESULTS: SEER registry results show over the 10-year time horizon average annual GIST incidence was 0.32 per 100,000 persons in the United States, 15-year limited-duration prevalence was 1.62 per 100,000 persons, and 3-year survival was 73%. A total of 292 GIST patients were included in the SEER-Medicare analyses; 35 were identified with probable recurrence. GIST patients had increased risk of mortality (hazard ratio: 1.23; 95% confidence intervals: 0.94-1.61) compared to controls. Median recurrence-free and postrecurrence survival was 45 and 46 months, respectively. GIST patients incurred significantly higher medical care costs in the first year after initial resection, with $23,221 attributable to GIST. GIST recurrence costs totaled $101,700 over 5 years after initial resection. CONCLUSIONS: GIST is associated with substantial medical care costs, estimated recurrence costs more than $100,000; treatments that delay or reduce recurrence could substantially reduce the burden of GIST.

Comparative efficacy of nilotinib and dasatinib in newly diagnosed chronic myeloid leukemia: a matching-adjusted indirect comparison of randomized trials.

OBJECTIVE: Nilotinib and dasatinib have not been directly compared in a randomized trial for the treatment of newly diagnosed chronic myeloid leukemia in the chronic phase (CML-CP). The purpose of this study was to indirectly compare rates of major molecular response (MMR), progression-free survival (PFS) and overall survival by month 12 with nilotinib and dasatinib treatment of newly diagnosed CML-CP. METHODS: Individual patient data from a randomized trial of nilotinib vs. imatinib (ENESTnd) and published summary data from a separate randomized trial of dasatinib vs. imatinib (DASISION) were utilized. A matching-adjusted indirect comparison was conducted by weighting individual patients treated with nilotinib to match baseline characteristics reported for dasatinib-treated patients, including age, gender, ECOG performance status and hematology lab values. After matching, efficacy outcomes were compared for patients treated with nilotinib 300 mg twice daily vs. dasatinib 100 mg once daily. Patients randomized to imatinib 400 mg once daily in each trial were used to assess the adequacy of the matching. RESULTS: Before matching, patients randomized to nilotinib in ENESTnd (n = 273) were older, with a lower median platelet count and more favorable performance status compared to patients randomized to dasatinib in DASISION (n = 259). After matching, all baseline characteristics were balanced across treatment groups. Matched patients treated with nilotinib vs. dasatinib experienced significantly higher rates of MMR (56.8 vs. 45.9%, p = 0.014) and overall survival (99.5 vs. 97.3%, p = 0.046) and numerically higher rates of PFS (98.8 vs. 96.5%). Matched imatinib arms showed no statistically significant or clinically meaningful differences in these outcomes. LIMITATIONS: Baseline measures unavailable in one or both trials could not be matched. Adverse event rates were not formally compared across trials due to differences in reporting. CONCLUSION: Nilotinib was associated with significantly higher rates of MMR and overall survival compared with dasatinib by month 12 in the treatment of newly diagnosed CML-CP.

Retrospective real-world comparison of medical visits, costs, and adherence between nilotinib and dasatinib in chronic myeloid leukemia.

OBJECTIVE: To compare healthcare resource utilization, costs, and treatment adherence associated with dasatinib versus nilotinib treatment as second-line therapies in chronic myeloid leukemia (CML) patients. METHODS: Two large retrospective claims databases (01/1999-06/2009) were combined to identify CML patients (ICD-9 code 205.1x) who received one or more prescriptions of dasatinib or nilotinib. Studied patients had continuous enrollment ≥ 1 month prior to and after the index date, defined as the first prescription for dasatinib or nilotinib. Patients were followed for up to 6 months from the index date to the earliest of the termination of healthcare plan enrollment or end of data availability. Patients with bone marrow or stem cell transplant during the study period were excluded. Poisson regression models were used to compare healthcare resource utilization between the two groups. Results were reported as incidence rate ratios (IRR). Healthcare cost differences were estimated for each cost component using generalized linear models or two-part models. Treatment adherence was measured by the proportion of days covered (PDC) and compared using generalized linear models. Multivariate regressions were used to control for potential confounding factors. RESULTS: A total of 521 CML patients receiving second-line tyrosine kinase inhibitors (TKI) (452 dasatinib and 69 nilotinib) were studied. During the study period, dasatinib patients were estimated to have more than twice as many inpatient days (IRR = 2.44; p < 0.001) and nearly double the number of inpatient admissions (IRR = 1.99; p = 0.047) compared to nilotinib patients. Over the follow-up period, dasatinib patients incurred $8828 more in total medical service costs (p < 0.001); cost differences were mainly driven by an adjusted inpatient cost difference of $8520 (p = 0.003). Dasatinib patients were less adherent, with a PDC value approximately 13% lower compared to nilotinib patients (p = 0.009). CONCLUSIONS: Among CML patients treated with second-line TKIs, nilotinib patients were more adherent and experienced lower healthcare resource utilization, resulting in medical service cost savings compared to dasatinib patients.