Frontline treatment patterns and attrition rates by subsequent lines of therapy in patients with newly diagnosed multiple myeloma.

BACKGROUND: For patients with multiple myeloma (MM), each additional line of therapy (LOT) is associated with lower response rates, shorter treatment duration and treatment-free intervals, and increased rates of toxicities and comorbidities. Here, we examine frontline treatment patterns, and attrition rates by LOT among newly diagnosed MM (NDMM) patients in the United States who were eligible or ineligible for autologous stem cell transplant (ASCT). METHODS: Data were identified from three US patient-level databases collectively covering the period January 2000 to September 2018. Patients had an index diagnosis of MM on or after January 1, 2007, medical and prescription insurance coverage at diagnosis, a 1-year look-back period prior to the index diagnosis, no prior malignancies in the 1-year period before index diagnosis, and had received ≥1 LOT. RESULTS: Among patients who did not receive ASCT (non-transplant; n = 22,062), 12,557 (57%) received only 1 LOT and 9505 (43%) received > 1 LOT. Patients receiving only 1 LOT were significantly older, had higher mean Charlson Comorbidity Index (CCI) scores, and higher incidences of comorbidities. Among the 2763 patients receiving ASCT, 2184 received > 1 LOT, and 579 (21%) received only 1 LOT (ie, ASCT was the last treatment). 1682 (61%) patients received induction therapy as frontline treatment, of whom 187 (11%) also received consolidation therapy. The latter group was younger than those who received only induction therapy, had lower mean CCI scores, and comparable or lower incidences of selected comorbidities. The most common frontline therapy for non-transplant and transplant-eligible patients was bortezomib/dexamethasone and bortezomib/lenalidomide/dexamethasone, respectively. Attrition rates across all LOTs were high for non-transplant patients (range, 43-57%) and transplant patients (range, 21-37%). Treatment duration decreased by LOT for non-transplant patients and was consistent across LOTs for transplant patients. CONCLUSIONS: In this analysis, a substantial proportion of patients with NDMM who received frontline therapy did not appear to receive a subsequent LOT. These high attrition rates underscore the need to use the most optimal treatment regimens upfront rather than reserving them for later LOTs in which the clinical benefit may decrease.

Impact of subsequent metastases on costs and medical resource use for prostate cancer patients initially diagnosed with localized disease.

BACKGROUND: The impact of subsequent metastases on costs and medical resource use (MRU) for prostate cancer (PC) patients initially diagnosed with localized disease was estimated. METHODS: Surveillance, Epidemiology, and End Results data, linked to Medicare (1999-2012), were used to identify 7482 patients diagnosed with subsequent metastases 12 months or more after the initial diagnosis of localized PC (cases), and they were matched to 25,709 localized PC patients without subsequent metastases (controls). Patients were followed for costs and MRU from 12 months before their index date (subsequent metastases or a matched date for controls) up to 12 months after it. Costs and MRU were stratified by the setting/type of care/service. Multivariate mixed effects regression analyses were used to construct and compare longitudinal trajectories of marginal predicted costs and predicted probabilities of MRU between cases and controls. RESULTS: Among the controls, predicted monthly costs remained relatively stable throughout the entire observation period (weighted mean per patient per month, $2746; range during 24 months, $2603-2858). In contrast, among the cases, costs increased from $2622 (95% confidence interval [CI], $2525-2719) 12 months before the diagnosis of subsequent metastases to $4767 (95% CI, $4623-4910) 1 month before the diagnosis of subsequent metastases, peaked during the month of metastases at $13,291 (95% CI, $13,148-13,435), and remained significantly higher than costs for the controls thereafter (eg, $4677 at + 12 months; 95% CI, $4549-4805). Costs and MRU increased across a wide range of settings/types, including inpatient, outpatient, home health, and hospice settings. CONCLUSIONS: In PC patients initially diagnosed with localized disease, a diagnosis of subsequent metastases is associated with substantially increased costs and MRU. Cancer 2017;123:3591-601. © 2017 American Cancer Society.

Daratumumab monotherapy compared with historical control data in heavily pretreated and highly refractory patients with multiple myeloma: An adjusted treatment comparison.

Daratumumab is a human CD38-directed monoclonal antibody approved in the United States as monotherapy for patients with multiple myeloma (MM) who have received ≥3 prior lines of therapy (LOTs), including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or who are double refractory to a PI and an IMiD, and in combination with lenalidomide/dexamethasone or bortezomib/dexamethasone for patients with MM who have received ≥1 prior LOT. This study compared the efficacy of daratumumab monotherapy versus historical controls through adjusted treatment comparison. Patient-level data were pooled from two daratumumab monotherapy studies (16 mg/kg; GEN501 and SIRIUS) and two independent US databases (IMS LifeLink and OPTUM), which reflect treatments used in real-world patients with MM who received ≥3 prior LOTs or were double refractory to a PI and an IMiD. Using a multivariate proportional hazards regression model, the relative treatment effect of daratumumab versus historical controls was estimated, adjusting for imbalances in characteristics between cohorts. Baseline characteristics that differed between patients treated with daratumumab (N = 148) and historical control (N = 658) were prior treatment with pomalidomide (55% vs 15%) or carfilzomib (41% vs 28%) and triple/quadruple refractory status (64% vs 14%). The adjusted overall survival-hazard ratio (OS-HR) for daratumumab versus historical control was 0.33 (95% confidence interval, 0.24-0.46) compared with 0.46 (0.35-0.59) for unadjusted HR. Impact of adjustment was mainly driven by refractory status and prior pomalidomide/carfilzomib exposure. This adjusted treatment comparison suggests that daratumumab demonstrates improved OS compared with historical control data in heavily pretreated and highly refractory MM patients.

Analysis of Real-World Data on Overall Survival in Multiple Myeloma Patients With ≥3 Prior Lines of Therapy Including a Proteasome Inhibitor (PI) and an Immunomodulatory Drug (IMiD), or Double Refractory to a PI and an IMiD.

BACKGROUND: This retrospective study evaluated the treatment patterns in and overall survival (OS) of multiple myeloma (MM) patients who were refractory to a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) or who had received three or more prior lines of therapy (LOTs) including a PI and an IMiD. METHODS: Electronic health records in the IMS LifeLink and OPTUM databases were screened for indexing periods of 2000-2014 and 2007-2014, respectively. Patients who were refractory to both a PI and an IMiD (criterion 1) or who received three or more prior LOTs (including a PI and an IMiD) and showed disease progression within 60 days of their most recent regimen (criterion 2) comprised the eligible population. Median OS from time of last LOT was assessed for the full cohort, cohorts meeting criteria 1 and 2, and clinically important subgroups. RESULTS: Of 3,929 and 3,837 patients with MM diagnoses evaluated in the IMS LifeLink and OPTUM databases, 500 and 162 met the eligibility criteria, respectively. Similar median OS was observed for eligible patients in the IMS LifeLink and OPTUM databases (7.9 vs. 7.9 months; p = .5358). In subgroup analyses of the IMS LifeLink data set, median OS was longer in patients <65 years of age than it was for those ≥65 years at eligibility (9.5 vs 6.7 months; p < .01) and in patients with good or unreported versus poor performance status at last claim (7.8 or 8.8 vs. 2.9 months; p < .0001). CONCLUSION: The findings of this survival analysis suggest that outcomes for these patients remain poor despite the availability of newer agents. IMPLICATIONS FOR PRACTICE: This real-world retrospective study of electronic health records examines the survival outcomes of patients with multiple myeloma who are heavily pretreated or highly refractory to currently approved treatments, including recently approved proteasome inhibitors and immunomodulatory drugs. This survival analysis showed that outcomes for these patients remain poor despite the availability of newer agents, with median overall survival of approximately 8 months. These findings highlight a critical need to develop novel therapies for these patients and also serve as a reference point against which emerging agents for heavily pretreated or highly refractory disease may be evaluated.

Pharmaceutical portfolio management: global disease burden and corporate performance metrics.

BACKGROUND: Biopharmaceutical companies face multiple external pressures. Shareholders demand a profitable company while governments, nongovernmental third parties, and the public at large expect a commitment to improving health in developed and, in particular, emerging economies. Current industry commercial models are inadequate for assessing opportunities in emerging economies where disease and market data are highly limited. OBJECTIVE: The purpose of this article was to define a conceptual framework and build an analytic decision-making tool to assess and enhance a company's global portfolio while balancing its business needs with broader social expectations. METHODS: Through a case-study methodology, we explore the relationship between business and social parameters associated with pharmaceutical innovation in three distinct disease areas. The global burden of disease-based theoretical framework using disability-adjusted life-years provides an overview of the burden associated with particular diseases. The social return on investment is expressed as disability-adjusted life-years averted as a result of the particular pharmaceutical innovation. Simultaneously, the business return on investment captures the research and development costs and projects revenues in terms of a profitability index. CONCLUSIONS: The proposed framework can assist companies as they strive to meet the medical needs of populations around the world for decades to come.

Comparative effectiveness of ciltacabtagene autoleucel in CARTITUDE-1 versus physician's choice of therapy in the Flatiron Health multiple myeloma cohort registry for the treatment of patients with relapsed or refractory multiple myeloma.

Introduction: Ciltacabtagene autoleucel (cilta-cel) is a novel chimeric antigen receptor T-cell therapy that is being evaluated in the CARTITUDE-1 trial (NCT03548207) in patients with relapsed or refractory multiple myeloma (RRMM) who received as part of their previous therapy an immunomodulatory drug, proteasome inhibitor, and an anti-CD38 monoclonal antibody (i.e., triple-class exposed). Given the absence of a control arm in CARTITUDE-1, this study assessed the comparative effectiveness of cilta-cel and physician's choice of treatment (PCT) using an external real-world control arm from the Flatiron Health multiple myeloma cohort registry. Methods: Given the availability of individual patient data for cilta-cel from CARTITUDE-1 and PCT in Flatiron, inverse probability of treatment weighting was used to adjust for unbalanced baseline covariates of prognostic significance: refractory status, cytogenetic profile, International Staging System stage, time to progression on last regimen, number of prior lines of therapy, years since diagnosis, and age. Comparative effectiveness was estimated for progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS). A range of sensitivity analyses were conducted. Results: Baseline characteristics were similar between the two cohorts after propensity score weighting. Patients with cilta-cel had improved PFS (HR: 0.18 [95% CI: 0.12, 0.27; p < 0.0001]), TTNT (HR: 0.15 [95% CI: 0.09, 0.22; p < 0.0001]), and OS (HR: 0.25 [95% CI: 0.13, 0.46; p < 0.0001]) versus PCT. Cilta-cel treatment benefit was robust and consistent across all sensitivity analyses. Conclusion: Cilta-cel demonstrated significantly superior effectiveness over PCT for all outcomes, highlighting its potential as an effective therapy in patients with triple-class exposed RRMM.

Real world treatment utilization patterns in patients with castration-resistant prostate cancer.

BACKGROUND: Studies describing treatment utilization for castration-resistant prostate cancer (CRPC) are limited. We aimed to describe the treatment utilization of a contemporary population-based CRPC cohort between 2006 and 2016. METHODS: We identified 1699 men with a PC diagnosis between 2005 and 2015, who developed CRPC between 2006 and 2015 in the Stockholm region of Sweden. Demographic information, stage and grade at PC diagnosis, stage at CRPC, prostate-specific antigen (PSA) nadir, PSA doubling time, treatment utilization rate within 1 year of CRPC diagnosis, reason for stopping therapy, treatment sequence trajectory, overall and PC specific survival was described. RESULTS: Treatment for men with de novo metastatic disease (n = 463) was 32%, treatment for men with progressive metastatic disease after PC diagnosis (n = 66) was 44%, treatment for men with nonmetastatic CRPC (n = 113) was 34% and treatment for those with an unknown stage at time of CRPC diagnosis (n = 857) was 12%. Docetaxel was used in 39%, abiraterone acetate plus prednisone in 15%, enzalutamide in 13%, cabazitaxel in 11% and radium-223 in 5% of treatments. Treatment increased from 22% in 2006-2009 for metastatic cancer to 50% in 2013-2015 (p < .001). Factors associated with treatment were an unknown stage at diagnosis (OR: 0.3, 95% CI: 0.2-0.4), age ≥75 years (OR: 0.2, 95% CI: 0.1 - 0.3), PSA doubling time >3 months (OR: 0.4, 95% CI: 0.3 - 0.6) and a diagnosis between 2013 and 2015 (OR: 3.4, 95% CI: 2.0 - 5.8). CONCLUSIONS: Despite treatment availability, in this large real-world cohort we found treatment utilization to remain low.

Treatment Pattern and Outcomes in Newly Diagnosed Multiple Myeloma Patients Who Did Not Receive Autologous Stem Cell Transplantation: A Real-World Observational Study : Treatment pattern and outcomes in patients with multiple myeloma.

INTRODUCTION: The objective of this study was to describe the treatment patterns among patients with newly diagnosed multiple myeloma (MM) who had not received autologous stem cell transplantation (ASCT). It further compares the safety and clinical outcomes across different frontline regimens as well as explores whether treatment duration predicts outcomes. METHODS: Patients with MM (> 45 years) who had not received ASCT were retrospectively identified from the US SEER-Medicare (Jan 2007-Dec 2016) and Optum (Jan 2007-Sep 2018) databases. Cox proportional hazard models were used to compare overall survival (OS) among bortezomib + lenalidomide + dexamethasone regimen (VRd), lenalidomide + dexamethasone regimen (Rd), cyclophosphamide + bortezomib + dexamethasone regimen (CyBorD), bortezomib + dexamethasone regimen (Vd), and other bortezomib-containing therapies based on propensity score matching. To address immortal time bias, time-fixed and time-dependent Cox models were employed to estimate the association of longer frontline treatment exposure with outcomes. RESULTS: Mean (standard deviation; SD) age was 71 (9.8) years; and 49.51% were women. Bortezomib and lenalidomide-based combinations were the most common treatment modalities. After matching, the HR (95% CI) of OS by frontline therapies comparing VRd with Vd was 0.76 (0.66, 0.86), CyBorD was 0.87 (0.75, 1.05), for other bortezomib-based therapies was 0.56 (0.49, 0.64), Rd was 0.83 (0.73, 0.95), and for other therapies was 0.70 (0.61, 0.80). Longer frontline treatment duration was associated with better OS for overall frontline [HR (95% CI) 0.86 (0.82, 0.90)]; Vd [0.81 (0.74, 0.89)]; CyBorD [0.79 (0.64, 0.98)] and Rd [0.86 (0.78, 0.95)]. CONCLUSION: Results demonstrated that the frontline therapies prescribed to most patients who did not receive ASCT for MM in the United States were consistent with the NCCN guideline recommendations. Longer frontline treatment duration was associated with improved OS.

Patient characteristics and outcomes after ruxolitinib discontinuation in patients with myelofibrosis.

Background: This retrospective analysis evaluates morbidities, outcomes and associated risk factors in patients with myelofibrosis (MF) after ruxolitinib discontinuation, using Truven Health Analytics MarketScan (TR), Optum integrated virtual electronic health records and claims databases (OP), and Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (SM).Methods: A total of 290 patients with MF between 2006 and 2015 (using ICD-9 and ICD-O-3 codes), who were treated with and discontinued ruxolitinib were identified. Only patients with ≥90 days of medical history prior to index diagnosis (TR + OP) and Part A, B, and D enrollment at the time of index diagnosis (SM) were included. Morbidities were assessed during the 30-day period each following ruxolitinib initiation, prior to and post ruxolitinib discontinuation. Cumulative incidence of cytopenias and efficacy outcomes were evaluated from baseline.Results: Median age of patients was 68 years, with equal proportion of either gender. Median time to ruxolitinib discontinuation was 284 days and median follow-up after discontinuation was 70.9 days. The majority of patients were diagnosed with anemia and >30% of the patients received RBC transfusions during 30-day period prior to and the 30-day period post ruxolitinib discontinuation. After ruxolitinib discontinuation, half of the patients developed cytopenias. The median treatment progression-free survival, and overall survival after ruxolitinib discontinuation were 6.0 (4.4, 8.3) months and 11.1 (8.4, 14.5) months, respectively. Age at ruxolitinib discontinuation (HR [95% CI] = 2.071 [1.320, 3.248]), Charlson Comorbidity Index score (HR [95% CI] = 1.172 [1.093, 1.257]) and gender (HR [95% CI] = 1.620 [1.108, 2.369]) increased the risk of treatment progression (start of the subsequent treatment regimen) or death.Conclusion: Results from this large, retrospective, US population-based outcome analysis of MF patients show an increase in morbidity burden and identifies the risk factors of survival outcomes among real-world patients who have discontinued ruxolitinib.

Relationship Between Metastasis-free Survival and Overall Survival in Patients With Nonmetastatic Castration-resistant Prostate Cancer.

BACKGROUND: Metastasis-free survival (MFS) has been shown to be predictive of overall survival (OS) in hormone-sensitive localized prostate cancer. We evaluated the relationship between MFS and OS in nonmetastatic castration-resistant prostate cancer (nmCRPC). PATIENTS AND METHODS: A retrospective analysis of 1207 high-risk patients with nmCRPC from the SPARTAN study (clinicaltrials.gov, NCT01946204) was undertaken. Landmark analyses of MFS status at several time points from randomization were performed to minimize guarantee-time bias. Hazard ratio (HR) of death as a function of MFS status was estimated based on a Cox proportional hazards model with 2-sided 95% confidence interval (CI). Estimated HRs were adjusted for stratification factors. Correlation analysis was performed using the Fleischer method. RESULTS: At all time points, MFS status strongly predicted OS. At landmark time points of 6, 9, and 12 months, risk of death was significantly higher for patients with metastases versus those without (adjusted HR at 6 months = 4.12; 95% CI, 2.60-6.54; P < .0001). MFS was positively correlated with OS based on the Fleischer method (HR, 0.69; 95% CI, 0.69-0.70; P < .0001). Approximately one-half of the variability in OS can be explained by MFS. CONCLUSION: Metastasis development, regardless of time point, is associated with significantly greater risk of death in men with high-risk nmCRPC; hence, MFS is predictive of OS.

Time-to-event Outcomes in Men with Nonmetastatic Castrate-resistant Prostate Cancer-A Systematic Literature Review and Pooling of Individual Participant Data.

CONTEXT: Until recently, there has been a lack of evidence-based treatment alternatives in men with nonmetastatic castrate-resistant prostate cancer (NM-CRPC). However, new evidence-based treatment alternatives are emerging. OBJECTIVE: We aimed to describe time-to-event outcomes in NM-CRPC patients based on evidence from both prospective and retrospective studies. Second, we aimed to describe predictors of these outcomes in the same patient population. EVIDENCE ACQUISITION: A systematic review was conducted to identify clinical studies (both prospective and retrospective) in NM-CRPC patients. All published Kaplan-Meier curves were digitized, and individual participant data were extracted using a published and validated R code. The following outcomes were considered: overall survival (OS), bone metastasis-free survival (BMFS), time to bone metastasis (TTBM), metastasis-free survival, time to metastasis, time to progression (TTP), progression-free survival, and time to prostate-specific antigen (PSA) progression. Second, we described all predictor/outcome relationships. EVIDENCE SYNTHESIS: Median survival times, in months, for OS, BMFS, TTBM, and TTP in placebo arms of randomized clinical trials are 45.3 (95% confidence interval [CI]: 43.5-46.8), 31.5 (95% CI: 28-33.4), 28.8 (95% CI: 25.2-31.6), and 22.2 (95% CI: 19.3-24.8), respectively. In general, reported outcomes in retrospective studies seemed to be longer than those reported in clinical trials. Baseline PSA nadir levels, PSA doubling time, PSA velocity, and alkaline phosphatase velocity are reliable predictors of time-to-event outcomes in NM-CRPC patients, whereas Gleason score is not. CONCLUSIONS: NM-CRPC is a long-standing condition where effective treatments to slow down disease progression historically have been lacking. Compared with prospective studies, retrospective studies have had limited ability to correctly identify NM-CRPC patients and estimate time to different outcomes in NM-CRPC patients. PATIENT SUMMARY: For patients with nonmetastatic castration-resistant prostate cancer (NM-CRPC), currently no effective treatments resulting in longer survival compared with watchful waiting are available. On average, without additional treatment, half of these patients survive <45 mo after NM-CRPC diagnosis.

Disease and Treatment Characteristics of Men Diagnosed With Metastatic Hormone-Sensitive Prostate Cancer in Real Life: Analysis From a Commercial Claims Database.

BACKGROUND: Our understanding of the clinical characteristics and treatment patterns of men who present with newly diagnosed metastatic (M1) hormone-sensitive prostate cancer is based mainly on clinical trial data. We sought to characterize the M1 population seen in routine clinical practice using a commercial claims database. PATIENTS AND METHODS: A US claims (2000-2013) database was used to identify patients with an index diagnosis of prostate cancer. M1 patients were identified by "International Classification of Diseases, 9th revision, Clinical Modification" diagnosis codes of metastasis to bone, viscera, distant lymph node, and unspecified sites within 90 days of the prostate cancer diagnosis. Progression to castration-resistant prostate cancer was identified by exposure to ≥ 1 drugs approved for castration-resistant prostate cancer, including docetaxel, abiraterone acetate, cabazitaxel, enzalutamide, sipuleucel-T, mitoxantrone, estramustine, and radium-223. RESULTS: Among 326,907 patients with an index prostate cancer diagnosis, 9199 (2.8%) had M1 disease, including 6955 with specified metastatic disease involving the bone (77%), viscera (38%), or lymph nodes (21%). The initial treatment of M1 disease was castration in 51%, localized therapy in 16%, prostate cancer drug only in 18%, and no treatment in 15%. The median time to first castration was 33 days. CONCLUSION: The proportion of men with prostate cancer who presented with M1 disease was consistent with other observations. Only 51% of the patients were treated according to national guidelines recommending medical or surgical castration. The proportion with visceral involvement at presentation was greater than expected from the clinical trials data in the same population. Just as seen in other medical conditions, clinical trial data are not representative of real-life patients seen in routine clinical practice.

Treatment evolution for metastatic castration-resistant prostate cancer with recent introduction of novel agents: retrospective analysis of real-world data.

Despite increasing drug treatment options for metastatic castration-resistant prostate cancer (mCRPC) patients, real-world treatment data are lacking. We conducted retrospective analyses of commercial claims and electronic medical record (EMR) databases to understand how treatment patterns for mCRPC have changed in a US-based real-world population. Truven Health Analytics MarketScan(®) (2000-2013) and EMR (2004-2013) databases were used to identify patients with an index prostate cancer diagnosis (ICD-9 codes 185X or 233.4X) and prescription claims for an mCRPC drug (mitoxantrone, estramustine, docetaxel, sipuleucel-T, cabazitaxel, abiraterone acetate, enzalutamide, or radium-223). Regimen analyses for first line of therapy (LOT1), second line of therapy, and beyond were performed among cohorts based on year of first mCRPC drug usage. mCRPC drug usage and treatment duration were compared across cohorts and age groups within each cohort. The commercial claims cohort yielded 3437 evaluable patients. Most men (91%) commencing mCRPC treatment had docetaxel as LOT1 in 2010; this number had declined to 15% in 2013. In 2013, 67% and 9% of patients used abiraterone acetate and enzalutamide, respectively, as LOT1. Among both commercial claims and EMR cohorts, treatment pattern changes were most pronounced in men aged >80 years, and median treatment duration for some mCRPC drugs was shorter than expected based on available clinical trial information. These results demonstrate a shift in mCRPC treatments during the past 5 years, with greater use of newer noncytotoxic treatments than docetaxel. These real-world data aid in understanding the changing role of chemotherapy in the management of mCRPC.

Prevalence of Prostate Cancer Clinical States and Mortality in the United States: Estimates Using a Dynamic Progression Model.

OBJECTIVE: To identify patient populations most in need of treatment across the prostate cancer disease continuum, we developed a novel dynamic transition model based on risk of disease progression and mortality. DESIGN AND OUTCOME MEASUREMENTS: We modeled the flow of patient populations through eight prostate cancer clinical states (PCCS) that are characterized by the status of the primary tumor, presence of metastases, prior and current treatment, and testosterone levels. Simulations used published US incidence rates for each year from 1990. Progression and mortality rates were derived from published clinical trials, meta-analyses, and observational studies. Model outputs included the incidence, prevalence, and mortality for each PCCS. The impact of novel treatments was modeled in three distinct scenarios: metastatic castration-resistant prostate cancer (mCRPC), non-metastatic CRPC (nmCRPC), or both. RESULTS AND LIMITATIONS: The model estimated the prevalence of prostate cancer as 2,219,280 in the US in 2009 and 3,072,480 in 2020, and incidence of mCRPC as 36,100 and 42,970, respectively. All-cause mortality in prostate cancer was estimated at 168,290 in 2009 and 219,360 in 2020, with 20.5% and 19.5% of these deaths, respectively, occurring in men with mCRPC. The majority (86%) of incidence flow into mCRPC states was from the nmCRPC clinical state. In the scenario with novel interventions for nmCRPC states, the progression to mCRPC is reduced, thus decreasing mCRPC incidence by 12% in 2020, with a sustained decline in mCRPC mortality. A limitation of the model is that it does not estimate prostate cancer-specific mortality. CONCLUSION: The model informs clinical trial design for prostate cancer by quantifying outcomes in PCCS, and demonstrates the impact of an effective therapy applied in an earlier clinical state of nmCRPC on the incidence of mCRPC morbidity and subsequent mortality.

Use of a claims database to characterize and estimate the incidence rate for Castleman disease.

Castleman disease (CD) is a rare lymphoproliferative disorder affecting single (unicentric; UCD) or multiple (multicentric; MCD) lymph nodes. The incidence of this difficult to diagnose disease is poorly understood, as no International Classification of Diseases, Ninth Revision (ICD-9) code is available. This study utilized a unique strategy to estimate its incidence using two commercial claims databases, IMS LifeLink™ and Truven Health Analytics MarketScan(®). Patients with an index diagnosis of lymphadenopathy (ICD-9 code 785.6) were followed longitudinally for 1 year prior to and 2 years post-index diagnosis date. An algorithm that identifies potential patients with CD was developed to determine the incidence rate in person-years. The incidence rate for CD was calculated as 21 (IMS LifeLink™) and 25 (MarketScan(®)) per million person-years. Additionally, 23% of patients with CD were identified as potentially suffering from MCD. These results are consistent with the definition of an orphan disease, and the low incidence of the disease estimated in the literature.

Diabetic peripheral neuropathy: resource utilization and burden of illness.

INTRODUCTION: Diabetic peripheral neuropathy (DPN) is a debilitating complication of diabetes and accounts for significant morbidity by pre-disposing the foot to ulceration and lower extremity amputation. Using a large US commercial claims database, this study analyzes the drug class usage and co-morbidities associated with DPN as well as estimates the associated economic burden. METHODS: Patients older than 18 and diagnosed with DPN were followed longitudinally for 2 years pre- and post-diagnosis date. Patients were analyzed for age, gender, hospital visits, ER and doctor's office visits, pharmacy claims, co-morbidities, and drug classes prescribed pre- and post-DPN diagnosis. The economic impact post-diagnosis of DPN was compared to the patients' pre-diagnosis resource use. RESULTS: In total, 10,982 incident DPN patients were identified, with a median age of 61 years, and an equal gender distribution. Post-DPN diagnosis, there was a 20% increase in the number of patients visiting hospitals and a 46% increase in the number of visits to hospitals. Further, there was a 46% increase in the annual cost per patient associated with visits to the hospitals, emergency room (ER), doctor's office, and pharmacy claims. As per the analysis presented in this study, increase in the number of visits, cost per visit, and number of patients visiting hospitals, ER and doctor's offices added up to a 46% increase in aggregated cost associated with Medical Resource Utilization (MRU) owing to DPN, with the highest increase (60%) in costs associated with hospitalization of patients with DPN. CONCLUSION: This study highlights the high economic burden associated with DPN. The results indicate that resource use significantly increases post-diagnosis of DPN, which leads to an increase in costs for payers. A noticeable proportion of patients with DPN had a pain co-diagnosis signifying the need for treatments that can effectively manage painful DPN.

Characterization of treatment resistant depression episodes in a cohort of patients from a US commercial claims database.

CONTEXT: Treatment Resistant Depression (TRD) is a significant and burdensome health concern. OBJECTIVE: To characterize, compare and understand the difference between TRD and non-TRD patients and episodes in respect of their episode duration, treatment patterns and healthcare resource utilization. DESIGN AND SETTING: Patients between 18 and 64 years with a new diagnosis of major depressive disorder (MDD) and without a previous or comorbid diagnosis of schizophrenia or bipolar disease were included from PharMetrics Integrated Database, a claims database of commercial insurers in the US. Episodes of these patients in which there were at least two distinct failed regimens involving antidepressants and antipsychotics were classified as TRD. PATIENTS: 82,742 MDD patients were included in the analysis; of these patients, 125,172 episodes were identified (47,654 of these were drug-treated episodes). MAIN OUTCOME MEASURES: Comparison between TRD and non-TRD episodes in terms of their duration, number and duration of lines of treatment, comorbidities, and medical resource utilization. RESULTS: Of the treated episodes, 6.6% (N = 3,134) met the criteria for TRD. The median time to an episode becoming TRD was approximately one year. The mean duration of a TRD episode was 1,004 days (vs. 452 days for a non-TRD episode). More than 75% of TRD episodes had at least four lines of therapy; half of the treatment regimens included a combination of drugs. Average hospitalization costs were higher for TRD than non-TRD episodes: $6,464 vs. $1,734, as were all other health care utilization costs. CONCLUSIONS: While this study was limited to relatively young and commercially covered patients, used a rigorous definition of TRD and did not analyze for cause or consequence, the results highlight high unmet medical need and burden of TRD on patients and health care resources.

Healthcare resource use in advanced prostate cancer patients treated with docetaxel.

OBJECTIVE: Although the treatment of metastatic castrate-resistant prostate cancer (mCRPC) has improved with newer therapies, there is little understanding how these therapies have impacted resource use and associated expenditures; available estimates are dated. The current study examined contemporary healthcare utilization and associated costs for mCRPC patients and how these measures changed over time. METHODS: This retrospective cohort analysis used medical and pharmaceutical insurance claims data from a large non-payer-owned integrated claims database of US commercial insurers. Amongst all patients with a prostate cancer diagnosis (n=256,464), those with ≥ 1 docetaxel claim (docetaxel cohort, n=3642) were identified as mCRPC patients. Within the docetaxel cohort, an additional 6-months follow-up cohort (n=2862) was identified, i.e., patients with at least 6 months of follow-up after the first docetaxel claim. Resource utilization and costs were identified for all-cause hospitalizations, emergency room (ER) visits, physician visits and ambulatory visits, and prostate cancer-related prescription treatments. RESULTS: Significant increases in the mean per-patient-per-month (PPPM) count for the docetaxel cohort were observed for all medical resources measured (hospitalizations and ER, physician, and ambulatory visits) in the post-docetaxel period compared with the pre-docetaxel period (p<0.0001); similar significant increases were observed for the 6-months follow-up cohort in the last 6 months (prior to lost to follow-up date) compared with the period preceding the last 6 months (p<0.0408 ambulatory visits, p<0.0001 all other resources). Total docetaxel cohort costs (mean [standard deviation]) rose from an average PPPM cost of US$2593 (3208) in the pre-docetaxel period to US$5847 (6990) in the post-docetaxel period (p<0.0001); each of the individual resources measured (hospitalization, all healthcare visits, and prescription costs) demonstrated significant increases (p<0.0001). LIMITATIONS: Retrospective study design. CONCLUSIONS: This large database analysis showed a significant increase in use of healthcare resources and associated costs among mCRPC patients following first-line docetaxel treatment.

The burden of chronic low back pain with and without a neuropathic component: a healthcare resource use and cost analysis.

BACKGROUND: This research addresses the need for population-based studies on the burden of chronic low back pain (CLBP) by examining healthcare service use and costs for patients with and without neuropathic components in the US population. METHODS: Data were analyzed from PharMetrics IMS LifeLink™ US Claims Database (2006-2008). Patients (≥18 years) with 36 months continuous enrollment, ICD-9 code for low back pain, and claims in 3 out of 4 consecutive months in the 12-month prospective period were included and classified with CLBP. Patients were further classified with a neuropathic component (wNP) and without a neuropathic component (woNP) based on ICD-9 codes. Healthcare resources, physical therapy, prescription medication use, and associated costs were assessed for the period January 1-December 31, 2008. RESULTS: A number of patients (39,425) were identified with CLBP (90.4% wNP). Patients wNP included more women, were older and more likely to have clinically diagnosed depression, and made significantly greater use of any prescription medication at index event, opioids (particularly schedule II), and healthcare resources. Total direct costs of CLBP-related resource use were ∼US$96 million over a 12-month follow-up. CLBP wNP accounted for 96% of total costs and mean annual cost of care/patient was ∼160% higher than CLBP patients woNP (US$ 2577 vs US$ 1007, p < 0.0001). LIMITATIONS: This study was descriptive and was not designed to demonstrate causality between diagnosis, treatment, and outcomes. Resource use and costs for reasons other than LBP were not included. Patients with neuropathic pain are more likely to seek treatment; therefore CLBP patients with a non-neuropathic component may be under-represented. CONCLUSIONS: The disproportionately high share of interventional resource use in CLBP wNP suggests greater need for new treatment options that more comprehensively manage the range of pain symptoms and signaling mechanisms involved, to help improve patient outcomes and reduce the burden on healthcare systems.