Trends in overall mortality among US veterans with primary myelofibrosis.

BACKGROUND: Primary myelofibrosis [PMF] is a myeloproliferative neoplasm associated with reduced overall survival (OS). Management strategies for PMF have evolved over the last two decades, including approval of ruxolitinib as the first Janus kinase 1 (JAK1)/JAK2 inhibitor for patients with intermediate or high-risk myelofibrosis. This study assessed changes in mortality before and after ruxolitinib approval, independent of ruxolitinib treatment. METHODS: This retrospective study investigated mortality trends among US veterans with PMF in 2 time periods, pre-ruxolitinib approval (01/01/2007-12/31/2010) and post-ruxolitinib approval (01/01/2015-09/30/2018). Deidentified patient-level data were extracted from US Veterans Health Administration (VHA) databases using PMF diagnosis codes; index was the first PMF diagnosis date. The analysis included adults with ≥2 PMF claims during the analysis periods who were continuously enrolled in the VHA plan 1 calendar year prior to and 6 months post-index and had ≥1 available International Prognostic Scoring System (IPSS) risk factor (available factors were age > 65, hemoglobin < 10 g/dL, and white blood cell count > 25 × 109/L; each counted as one point). Patients with ≥1 MF diagnosis for 12 months before the index period were excluded. Ruxolitinib treatment was not a requirement to be included in the post-ruxolitinib approval cohort. Mortality rates and OS were estimated using the Kaplan-Meier approach; all-cause mortality hazard ratio was estimated using univariate Cox regression. RESULTS: The pre- and post-ruxolitinib approval cohorts included 193 and 974 patients, respectively, of which 80 and 197 had ≥2 IPSS risk factors. Ruxolitinib use in the post-ruxolitinib cohort was 8.5% (83/974). At end of follow-up, median (95% CI) OS was significantly shorter in the pre-ruxolitinib cohort (1.7 [1.2-2.6] years vs not reached [3.4-not reached]; P < 0.001). Overall mortality rates for the pre- versus post-ruxolitinib approval cohorts were 79.8% versus 47.3%, respectively, and overall risk of death was 53% lower in the post-ruxolitinib period (hazard ratio, 0.47; 95% CI, 0.37-0.58; P < 0.001). Mortality rates were lower among patients with < 2 vs ≥2 IPSS risk factors. CONCLUSIONS: Although veterans with PMF have high overall mortality rates, and results in this population might not be generalizable to the overall population, there was a significant lowering of mortality rate in the post-ruxolitinib period.

Chimeric Antigen Receptor T-Cell Access in Patients with Relapsed/Refractory Large B-Cell Lymphoma: Association of Access with Social Determinants of Health and Travel Time to Treatment Centers.

Large B-cell lymphoma (LBCL) is the most common type of non-Hodgkin lymphoma. Chimeric antigen receptor T-cell (CAR T) therapy represents a novel treatment with curative potential for relapsed or refractory (R/R) LBCL, but there are access barriers to this innovative therapy that are not well-studied. Study objectives were: (1) Assess the impact of geographic factors and social determinants of health (SDOH) on access to treatment with CAR T in a sample of patients with R/R LBCL and ≥2 prior lines of therapy (LOT). (2) Compare and contrast patient characteristics, SDOH, and travel time between patients with R/R LBCL who received CAR T and those who did not. An observational, nested case-control study of patients with R/R LBCL, ≥2 prior LOT, not in a clinical trial, identified using 100% Medicare Fee-For-Service and national multi-payer claims databases. Patients were linked to near-neighborhood SDOH using 9-digit ZIP-code address. Driving distance and time between residence and nearest CAR T treatment center (TC) was calculated. Patients were stratified based on treatments received upon third LOT initiation (Index Date) or later: (1) received CAR T and (2) did not receive CAR T. Multivariable logistic regression was used to evaluate factors associated with CAR T. 5011 patients met inclusion criteria, with 628 (12.5%) in the CAR T group. Regression models found the likelihood of receiving CAR T decreased with patient age (odds ratio [OR] = .96, P < .001), and males were 29% more likely to receive CAR T (OR = 1.29, P = .02). Likelihood of CAR T increased with Charlson Comorbidity Index (CCI; OR = 1.07, P < .001) indicating patients with more comorbidities were more likely to receive CAR T. Black patients were less than half as likely to receive CAR T than White patients (OR = .44, P = .01). Asian patients did not significantly differ from White patients (OR = 1.43, P = .24), and there was a trend for Hispanic patients to have a slightly lower likelihood of CAR T (OR = .50, P = .07). Higher household income was associated with receipt of CAR T, with the lowest income group more than 50% less likely to receive CAR T than the highest (OR = .44, P = .002), and the second lowest income group more than 30% less likely (OR = .68, P = .02). Finally, likelihood of CAR T therapy was reduced when the driving time to the nearest TC was 121 to 240 minutes (reference group: ≤30 minutes; OR = .64, P = .04). Travel times between 31 and 121 or greater than 240 minutes were not significantly different from ≤30 minutes. Payer type was collinear with age and could not be included in the regression analysis, but patients with commercial insurance were 1.5 to 3 times more likely to receive CAR T than other payers on an unadjusted basis. We identified significant disparities in access to CAR T related to demographics and SDOH. Patients who were older, female, low income, or Black were less likely to receive CAR T. The positive association of CCI with CAR T requires further research. Given the promising outcomes of CAR T, there is urgent need to address identified disparities and increase efforts to overcome access barriers.

Changes in the incidence and overall survival of patients with myeloproliferative neoplasms between 2002 and 2016 in the United States.

This analysis examined trends in incidence and survival among US adults with myeloproliferative neoplasms, including essential thrombocythemia (ET; n = 14,676), polycythemia vera (PV; n = 15,141), and primary myelofibrosis (PMF; n = 4214), using Surveillance, Epidemiology, and End User Results (SEER) data (SEER 18; 2002-2016). Incidence and survival rates over the study period and by diagnosis year (per 5-year time frames: 2002-2006; 2007-2011; 2012-2016) were assessed. The overall incidence rates (95% CI) were 1.55 (1.52-1.57) for ET, 1.57 (1.55-1.60) for PV, and 0.44 (0.43-0.45) per 100,000 person-years for PMF, with rising ET incidence. Five-year mortality over the study period was 19.2%, 19.0%, and 51.0% for ET, PV, and PMF, respectively. Improved survival over time was observed for PV and PMF, but not for ET. These findings highlight the need for effective ET therapies, as ET incidence has risen without concurrent improvements in survival over the past 2 decades.

Hospitalization risk in pediatric patients with bipolar disorder treated with lurasidone vs. other oral atypical antipsychotics: a real-world retrospective claims database study.

BACKGROUND: Real-world evidence on atypical antipsychotic (AAP) use in pediatric bipolar disorder is limited. OBJECTIVE: To assess the risk of all-cause and psychiatric hospitalization among pediatric patients with bipolar disorder when treated with lurasidone versus other atypical antipsychotics (AAPs). METHODS: This retrospective cohort study used commercial claims data (January 1, 2011 to June 30, 2017) to identify pediatric patients (age ≤17 years) with bipolar disorder treated with oral atypical antipsychotics (N = 16,201). The date of the first claim for an AAP defined the index date, with pre- and post-index periods of 180 days. Each month of the post-index period was categorized as monotherapy treatment with lurasidone, aripiprazole, olanzapine, quetiapine, or risperidone, no/minimal treatment, or other. The risk of all-cause and psychiatric hospitalizations (defined by a psychiatric diagnosis on the facility claim) was analyzed based on treatment in the current month, time-varying covariates (prior treatment-month classification, hospitalization in the prior month, emergency room visit in the prior month), and fixed covariates (age, gender, pervasive development disorder/mental retardation, disruptive behavior/conduct disorder, attention deficit hyperactivity disorder, depression, anxiety, adjustment disorder, obesity, diabetes, antidepressants, anxiolytics, other co-medication) using a marginal structural model. RESULTS: Treatment with aripiprazole (OR = 1.60, 95% CI: 1.08-2.36) and olanzapine (OR = 1.68, CI: 1.03-2.71) was associated with significantly higher odds of all-cause hospitalizations compared to lurasidone, but treatment with quetiapine (OR = 1.03, CI: 0.69-1.54) or risperidone (OR = 1.02, CI: 0.68-1.53) was not. Similarly, treatment with aripiprazole (OR = 1.61, 95% CI: 1.08-2.38) and olanzapine (OR = 1.73, CI: 1.06-2.80) was associated with significantly higher odds of psychiatric hospitalizations compared to lurasidone, but treatment with quetiapine (OR = 1.02, CI: 0.68-1.54) or risperidone (OR = 1.01, CI: 0.67-1.51) was not. CONCLUSION: In usual clinical care, pediatric patients with bipolar disorder treated with lurasidone had a significantly lower risk of all-cause and psychiatric hospitalizations when compared to aripiprazole and olanzapine, but not quetiapine or risperidone.

Development and Validation of an Inflammatory Bowel Disease Severity Index Using US Administrative Claims Data: A Retrospective Cohort Study.

BACKGROUND: Clinical indices to characterize the severity of inflammatory bowel disease (IBD) are widely used in clinical trials and real-world practice. However, there are few validated instruments for assessing IBD severity in administrative claims-based studies. METHODS: Patients (18-89 years) diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) and receiving ≥1 prescription claim for IBD therapy were identified using administrative claims data from the Optum Clinformatics, IMS PharMetrics, and Truven MarketScan databases (January 1, 2013-September 30, 2017). Regression modeling identified independent predictors of IBD-related hospitalization (inpatient stay or emergency department visit resulting in hospitalization), which were used to develop IBD severity indices. The index was validated against all-cause hospitalization and total cost and IBD-related hospitalization and total cost. RESULTS: There were 51,767 patients diagnosed with UC (n = 30,993) or CD (n = 20,774) who were initiated treatment with IBD therapy. Independent predictors of IBD-related hospitalization were Charlson Comorbidity Index score >1, anemia, weight loss, intravenous corticosteroid use, prior gastrointestinal-related emergency department visit and hospitalization, and unspecified disease location or more extensive disease. Female sex, renal comorbidities, intestinal fistula, and stricture were additional risk factors for patients with CD, whereas age <40 years was a UC-specific risk factor. Median IBD severity scores were 8 and 13 for UC and CD, respectively, from possible total scores of 51 and 37. Inflammatory bowel disease severity score correlated with significantly higher all-cause hospitalization and cost, all-cause total cost, IBD-related hospitalization cost, and total cost. CONCLUSIONS: These validated UC and CD severity indices can be used to predict IBD-related outcomes using administrative claims databases.

Healthcare resource utilization, costs and treatment patterns in patients with bipolar disorder treated with lurasidone or cariprazine.

OBJECTIVE: To compare healthcare resource utilization (HCRU), costs, and treatment adherence and persistence for patients with bipolar disorder treated with lurasidone or cariprazine. METHODS: Adult patients with bipolar disorder who initiated lurasidone or cariprazine as monotherapy or adjunctive therapy between 1 January 2016 and 30 June 2019 were identified from the IBM MarketScan Commercial and Medicare Supplemental Database. The date of the first claim for lurasidone or cariprazine was defined as the index date. A difference-in-difference (DID) analysis, which mitigated bias by using each cohort as its own control, compared the changes in HCRU and costs from 6-months pre-treatment (baseline) to 6-months post-treatment (follow-up) between the two cohorts. Treatment adherence (medication possession ratio and proportion of days covered) and persistence (time to discontinuation) were assessed during the 6-month post-treatment period. Adjusted analyses were conducted using inverse probability of treatment weighting on HCRU, costs, and time to discontinuation. RESULTS: A total of 16,683 patients treated with lurasidone and 4,128 patients treated with cariprazine were identified. Average age (39-40) and proportion female (68-71%) were similar between cohorts. Both cohorts had reductions in hospitalizations from baseline to follow-up, and the decrease was significantly greater for the lurasidone cohort compared to the cariprazine cohort (change in the proportions of patients with all-cause hospitalizations: -5.3% vs. -2.5%, DID = -2.8%, p<.001). The total healthcare costs increased from baseline to follow-up in both cohorts, and the increase was significantly lower for the lurasidone cohort (change in total all-cause healthcare cost per person: $3,413 vs. $4,642, DID=-$1,228, p = .022). The lurasidone cohort had significantly lower risk of discontinuing treatment (hazard ratio = 0.86, p<.001) than the cariprazine cohort. CONCLUSIONS: Patients with bipolar disorder treated with lurasidone had greater reductions in hospitalizations from 6-months pre-treatment to 6-months post-treatment and had a lower increase in total costs compared to patients treated with cariprazine.

Effects of early vs delayed progression on clinical and economic outcomes in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors as first-line therapy: results from the IMPACT RCC claims data analysis.

BACKGROUND: A key therapeutic goal of metastatic renal cell carcinoma (mRCC) treatment is delayed disease progression. The degree to which early therapeutic success affects downstream outcomes is not well established. OBJECTIVE: To assess the clinical and economic impact of early vs delayed disease progression in patients with mRCC treated with first-line (1L) tyrosine kinase inhibitors (TKIs) followed by second-line (2L) therapy in the US Veterans Health Administration (VHA) database. METHODS: Adult patients newly diagnosed with mRCC who were treated with a TKI as 1L therapy and who progressed to 2L therapy from October 1, 2013, through March 31, 2018, were identified from the US VHA database. Patients were stratified by median time from initiation of 1L therapy to initiation of 2L therapy into early (median time or sooner)and delayed (longer than the median) progression cohorts. Clinical outcomes (time to 2L therapy discontinuation, time to third-line [3L] treatment initiation, and overall survival) were assessed descriptively, and health care resource utilization and costs were compared between patients in the early and those in the delayed progression cohorts. Survival analyses (Kaplan-Meier curves) were used to estimate descriptively the median time to discontinuation, time to next line of treatment, and time to death for each cohort. Multivariate analysis was performed to adjust for the influence of differences in cohort characteristics, and Cox proportional hazards models were used to descriptively assess the impact of predictive factors on clinical outcomes. RESULTS: 289 patients were included in the analysis: 145 in the early progression cohort and 144 in the delayed progression cohort. Baseline characteristics were similar between the early and delayed progression cohorts. Median time from 1L therapy initiation to 2L therapy discontinuation was 7.9 months in the early progression cohort and 18.0 months in the delayed progression cohort, whereas time from 1L therapy initiation to 3L therapy initiation was 9.4 and 21.8 months, respectively; overall survival was 19.7 and 36.4 months, respectively. Descriptive analysis revealed generally lower risks for 2L therapy discontinuation (HR = 0.40, 95% CI = 0.31-0.52), 3L therapy initiation (HR = 0.42, 95% CI = 0.32-0.55), and death (HR = 0.46, 95% CI = 0.33-0.64) for those with delayed progression. After adjustment for possible confounding factors, comparative analysis during the follow-up period showed that delayed progression was associated with a shorter median all-cause hospital length of stay (0.4 days vs 0.8 days for early progression; P = 0.0004), fewer pharmacy visits (3.57 vs 4.08 visits; P = 0.0266), and lower total health care costs ($10,342 vs $13,388; P = 0.0347) per patient per month. CONCLUSIONS: In patients with mRCC, early progression after 1L therapy initiation is associated with generally worse clinical outcomes and statistically significantly greater health care resource utilization and costs than delayed progression. This finding highlights the importance of initiating therapy with an optimal 1L treatment regimen that has been proven to delay disease progression. DISCLOSURES This study was sponsored by EMD Serono Inc., an affiliate of Merck KGaA, and Pfizer Inc. EMD Serono Inc. and Pfizer Inc. were involved in the study design; the collection, analysis, and interpretation of the data; the writing of the report; and the decision to submit the report for publication. Liu and Bhanegaonkar are employed by EMD Serono Inc., an affiliate of Merck KGaA. Kasturi was employed by EMD Serono Inc., an affiliate of Merck KGaA, at the time of this study. Kim and Krulewicz are employed by Pfizer Inc. Dieyi is an employee of STATinMED Research, which received consulting fees from EMD Serono Inc. and Pfizer Inc. Hutson has received grants from Pfizer Inc., Astellas Pharma Inc., Janssen Pharmaceuticals, Exelixis, Inc., and Eisai Co., Ltd., outside of this work. Data from this analysis were presented at the Virtual International Society for Pharmacoeconomics and Outcomes Research 2020 conference, May 18-20, 2020; the virtual American Society of Clinical Oncology Annual Meeting, May 29-31, 2020; and AMCP Nexus 2020 Virtual, October 20-23, 2020.