Real-world survival of US patients with intermediate- to high-risk myelofibrosis: impact of ruxolitinib approval.

The Janus kinase inhibitor ruxolitinib is approved for the treatment of myelofibrosis (MF) and improved overall survival (OS) versus control therapy in the phase 3 COMFORT trials. The aim of this retrospective analysis was to examine the real-world impact of ruxolitinib on OS in patients with MF. The US Medicare Fee-for-Service claims database (parts A/B/D) was used to identify patients with ≥ 1 inpatient or ≥ 2 outpatient claims with an MF diagnosis (January 2010-December 2017). Eligible patients with MF were ≥ 65 years old (intermediate-1 or higher risk based on age). Patients were divided into 3 groups based on ruxolitinib approval status at diagnosis and ruxolitinib exposure: (1) preapproval, ruxolitinib-unexposed; (2) post-approval, ruxolitinib-unexposed; and (3) post-approval, ruxolitinib-exposed. In total, 1677 patients with MF were included (preapproval [all ruxolitinib-unexposed], n = 278; post-approval, n = 1399 [ruxolitinib-unexposed, n = 1127; ruxolitinib-exposed, n = 272]). Overall, median age was 78 years, and 39.8% were male. Among patients with valid death dates (preapproval, n = 119 [42.8%]; post-approval, ruxolitinib-unexposed, n = 382 [33.9%]; post-approval ruxolitinib-exposed, n = 54 [19.9%]), 1-year survival rates were 55.6%, 72.5%, and 82.3%, and median OS was 13.2 months, 44.4 months, and not reached, respectively. Risk of mortality was significantly lower post- versus preapproval regardless of exposure to ruxolitinib (ruxolitinib-unexposed: adjusted hazard ratio [HR], 0.67; ruxolitinib-exposed: adjusted HR, 0.36; P < 0.001 for both); post-approval, mortality risk was significantly lower in ruxolitinib-exposed versus ruxolitinib-unexposed patients (adjusted HR, 0.61; P = 0.002). Findings from this study complement clinical data of ruxolitinib in MF by demonstrating a survival benefit in a real-world setting.

Real-world treatment patterns of metastatic non-small cell lung cancer patients receiving epidermal growth factor receptor tyrosine kinase inhibitors.

BACKGROUND: Several epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) have been approved for first-line (1L) treatment of EGFR-mutated metastatic non-small cell lung cancer (mNSCLC) in the United States (US). Real-world analyses of 1L treatment patterns with EGFR TKIs, including the third-generation EGFR TKI osimertinib which was most recently approved in 2018, are still sparse. METHODS: This retrospective observational study used data from IQVIA's prescription claims (LRx) and medical claims (Dx) databases. mNSCLC patients newly treated with any EGFR TKI in the 1L setting were identified from January 1, 2015 to April 30, 2020; the first date of EGFR TKI (third-generation osimertinib, first-generation [erlotinib, gefitinib], or second-generation [afatinib, dacomitinib]) was the index date. Treatment patterns were reported in the cohorts stratified by 1L EGFR TKI. RESULTS: A total of 2505 patients were included in the study (982 osimertinib, 1060 first-generation, and 463 second-generation EGFR TKI). Beginning in 2018, osimertinib became the most common 1L EGFR TKI (66.7%) and in early 2020, it accounted for 90.6% of 1L EGFR TKIs. Nearly all patients (>97%) were treated with 1L EGFR TKI monotherapy. Patients with 1L osimertinib had longer treatment duration compared to patients with 1L first- or second-generation EGFR TKI (median months: 17.8 vs. 8.7 vs. 10.5, respectively; log-rank test for comparisons with osimertinib p < 0.0001) over median follow-up times of 9.8, 20.5, and 19.3 months. 32.5% and 36.3% of the first- and second-generation EGFR TKI cohorts, respectively, had evidence of 2L treatment. Osimertinib monotherapy accounted for the majority of 2L treatments (58.3%/60.7%) and 11.3%/8.9% had 2L chemotherapy or immuno-oncology therapy following 1L first- or second-generation EGFR TKI. CONCLUSION: In this real-world study of a US claims database, 1L treatment duration was longer with osimertinib compared with other EGFR TKIs. Future studies with longer follow-up are recommended to understand treatment patterns after progression on EGFR TKIs.

Economic burden of early-stage non-small-cell lung cancer: an assessment of healthcare resource utilization and medical costs.

Aim: To quantify the economic burden of early-stage non-small-cell lung cancer (NSCLC) among patients with and without adjuvant therapy. Methods: All-cause and NSCLC-related healthcare resource utilization and medical costs were assessed among patients with resected stage IB-IIIA NSCLC in the SEER-Medicare database (1 January 2011-31 December 2019), from NSCLC diagnosis to death, end of continuous enrollment, or end of data availability (whichever occurred first). Results: Patients receiving adjuvant therapy had the lowest mean NSCLC-related medical costs (adjuvant [n = 1776]: $3738; neoadjuvant [n = 56]: $5793; both [n = 47]: $4818; surgery alone [n = 3478]: $4892, per-person-per-month), driven by lower NSCLC-related hospitalization rates. Conclusion: Post-surgical management of early-stage NSCLC was associated with high economic burden. Adjuvant therapy was associated with numerically lower medical costs over surgical resection alone.

Ruxolitinib for myelofibrosis in elderly non-transplant patients: healthcare resource utilization and costs.

AIM: This study evaluated real-world healthcare resource utilization (HCRU), direct costs, and overall survival (OS) of patients who were Medicare beneficiaries and were newly diagnosed with myelofibrosis (MF) who filled ≥1 prescription of ruxolitinib versus those who did not. PATIENTS AND METHODS: This was a study of the US Medicare fee-for-service database. Beneficiaries were aged ≥65 years with an MF diagnosis (index) between January 1, 2012 - December 31, 2017. Data were summarized descriptively. OS was estimated using Kaplan-Meier analysis. RESULTS: Patients with ≥1 prescription fill of ruxolitinib (n = 2,787) had lower mean rates (per patient per month [PPPM]) versus patients who did not fill a prescription for ruxolitinib (n = 7,262) for hospitalizations (0.16 vs 0.32), length of inpatient stay (0.16 vs 2.44 days), emergency department visits (0.10 vs 0.14), physician office visits (4.68 vs 6.25), skilled nursing facility stays (0.02 vs 0.12), home health/durable medical equipment services (0.32 vs 0.47), and hospice visits (0.30 vs 1.70). Monthly medical costs were numerically lower in patients who had ≥1 fill of ruxolitinib versus those who did not fill a prescription for ruxolitinib ($6,553 vs $12,929), largely driven by inpatient costs ($3,428 vs $6,689). Pharmacy costs were $10,065 and $987 in patients who filled versus did not fill ≥1 prescription for ruxolitinib, respectively; total PPPM all-cause healthcare costs were $16,618 and $13,916, respectively. The median OS was 37.5 and 18.7 months for the cohorts of patients who filled versus did not fill ≥1 prescription for ruxolitinib, respectively (hazard ratio = 0.63, 95% CI = 0.59 - 0.67). CONCLUSIONS: Ruxolitinib is associated with reduced HCRU and direct costs of medical care in addition to increased survival, suggesting it to be a cost-effective advance for patients with MF.

Myelofibrosis is a rare bone marrow cancer. People with this disease do not live as long as the general population. They have difficult symptoms, can tire easily, and may have a large spleen that can be uncomfortable. Ruxolitinib is a treatment for myelofibrosis that can improve symptoms and help patients live longer.This study asked how treating patients with ruxolitinib affected three things. (1) How often do they go to a healthcare provider? (2) How much do they spend on their healthcare? (3) How long do they live? The authors looked at Medicare records to answer these questions.The study found that treated patients visited hospitals, doctors' offices, and other services less often. When they did require hospital care, they stayed in the hospital for a shorter amount of time. As a result, treated patients spent about half as much on these services. However, patients treated with ruxolitinib spent more at the pharmacy. Finally, treated patients lived about twice as long as those who were never treated with ruxolitinib. These findings suggest that ruxolitinib is worthwhile for patients with myelofibrosis.

Real-world study of disease-free survival & patient characteristics associated with disease-free survival in early-stage non-small cell lung cancer: A retrospective observational study.

INTRODUCTION/ BACKGROUND: Surgical resection remains standard of care for patients with early-stage non-small cell lung cancer (NSCLC), but research shows that adjuvant therapy can reduce the risk of disease recurrence. Our objective was to characterize disease-free survival (DFS) using real-world data. MATERIALS AND METHODS: This was a retrospective study using the COTA real-world database derived from electronic health records in the United States (US). Adults diagnosed with stage IB-IIIA NSCLC from 2013 to 2018 who underwent complete surgical resection (index date) for NSCLC were included. DFS was analyzed using the Kaplan-Meier method. A multivariable Cox-Proportional Hazard (PH) model stratified by year of diagnosis was developed to evaluate covariates associated with DFS. RESULTS: 703 patients met the study criteria (mean age 66.2 years, female (56%), White (82%), and median follow-up time was 37.4 months from index date. Approximately 48% of patients experienced recurrence or death with a median DFS of 42.9 months (95% CI: 37.4-52.2). Patients who received adjuvant therapy, neoadjuvant and adjuvant therapy, neoadjuvant therapy, and surgery only experienced a median DFS of 43.7, 32.3, 33.7, and 49.4 months, respectively. After adjustment, stage at diagnosis and adjuvant therapy status were significantly associated with DFS events. CONCLUSIONS: Higher stage at diagnosis and lack of adjuvant therapy were associated with greater risk of recurrence. Future research should focus on the adoption and effect of adjuvant/ neoadjuvant therapies on disease recurrence, including in patients with oncogenic driver mutations.

Diabetes-Related Complications and Costs in Medicare Beneficiaries with Comorbid Rheumatoid Arthritis and Diabetes Treated with Abatacept Versus Other Targeted DMARDs.

INTRODUCTION: Targeted DMARD (tDMARD) use in patients with rheumatoid arthritis (RA) and type 2 diabetes mellitus (T2DM) may increase whole-body insulin sensitivity. Evidence comparing the T2DM-related clinical and economic impact of abatacept versus other tDMARDs is limited. This study compared differences in T2DM-related healthcare resource utilization (HCRU) and costs in patients with RA and T2DM. METHODS: This retrospective study used 100% Medicare Fee-for-Service claims (parts A/B/D) to identify patients ≥ 65 age, diagnosed with RA and T2DM, and were either TNFi-experienced (switched from a TNFi to another tDMARD) or tDMARD-naïve, initiating their first tDMARD (abatacept, TNFi, or non-TNFi) between 2010 and 2017. Abatacept users were propensity-score (PS) matched to TNFi and other non-TNFi users separately on baseline demographics, comorbidities, medications, T2DM-related HCRU, and costs. Post-index follow-up: until discontinuation of index treatment, disenrollment, death, or end of study period, whichever occurred first. T2DM-related complications and HCRU were assessed. Costs were normalized to per-patient-per-month (PPPM) and inflated to 2019 US$. RESULTS: The TNFi-experienced group included 2169 abatacept/TNFi and 2118 abatacept/other non-TNFi PS-matched pairs; the tDMARD-naïve group included 2667 abatacept/TNFi and 2247 abatacept/other non-TNFi PS-matched pairs. For TNFi-experienced patients, T2DM-related complication rates for inpatient settings PPPM trended lower for abatacept than TNFi (21 vs. 24, p = 0.046) and other non-TNFi groups (21 vs. 26; p < 0.0001). T2DM-related total costs PPPM for TNFi-experienced patients demonstrated lower trends for abatacept than TNFi ($489 vs. $594, p = 0.016) and other non-TNFi users ($493 vs. $606, p = 0.012). CONCLUSIONS: Medicare beneficiaries with RA and T2DM who switch to/initiate abatacept as their first tDMARD have directionally lower rates and costs of T2DM-related complications compared with patients switching to/initiating other tDMARDs. Abatacept treatment may help reduce clinical and economic burdens associated with T2DM in patients with RA.

Thrombotic events and mortality risk in patients with newly diagnosed polycythemia vera or essential thrombocythemia.

Patients with polycythemia vera (PV) and essential thrombocythemia (ET) have increased thrombotic risk. This retrospective, real-world analysis of Medicare patients (age ≥ 65 years) newly diagnosed with high-risk PV or intermediate-/high-risk ET compared mortality risk among those with versus without thrombotic events during the study period. Patients diagnosed with PV or ET with ≥ 1 inpatient or ≥ 2 outpatient claims (January 1, 2010-December 31, 2017; index was date of first qualifying claim) were included. The study included 50,405 Medicare beneficiaries with PV and 124,569 with ET. During follow-up (median [range]: PV, 34.5 [0-97.3] months; ET, 25.5 [0-97.4] months), 14,334 patients (28.4%) with PV and 30,478 (24.5%) with ET experienced thrombotic events (most commonly ischemic stroke [PV, 46.0%; ET, 42.5%]. Mortality risk was increased for patients with versus without post-index thrombosis for both PV (adjusted hazard ratio [aHR; 95% CI], 18.6 [16.1-21.6]; P < 0.001) and ET (aHR [95% CI], 25.2 [23.1-27.5]; P < 0.001). Median survival was shorter for patients who experienced a thrombotic event ≤ 1 year post-index versus those who did not (PV, 5.1 years vs not reached; ET, 3.7 vs 6.7 years; both P < 0.001). These findings highlight the importance of thrombosis risk mitigation in PV and ET management.

Burden of illness and treatment patterns among patients with peripheral T-cell lymphoma in the US healthcare setting.

OBJECTIVE: Limited real-world information exists on the characteristics or treatment patterns of patients with peripheral T-cell lymphoma (PTCL). We reported demographics, treatments and direct healthcare resource utilization (HRU) in a large cohort of US patients newly diagnosed with PTCL. METHODS: Patients aged ≥18 years with a PTCL diagnosis between January 2011 and December 2016 were identified from the Inovalon MORE2 Registry. Continuous medical/pharmacy enrollment 6-months prior to and ≥1-month after the first PTCL diagnosis was required. The main focus of this study was on newly diagnosed patients receiving cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) versus other chemotherapy. RESULTS: A total 2971 patients with PTCL and chemotherapy information were included in the study; 1706 (57%) received CHOP and 1265 (43%) other chemotherapy. A majority of patients (51.7%) were female; mean (standard deviation) age at index was 61.0 (±16.0), Charlson score was 4.1 (±2.9), and follow-up time was 24.6 (±16.7) months. During the variable follow-up period, HRU was similar for the CHOP and other chemotherapy cohorts; 58.1% and 59.3% had ≥1 all-cause hospitalizations, respectively. The proportion of patients with ≥1 PTCL-related hospitalizations was higher in the CHOP than in the other chemotherapy cohort (40.3% vs. 9.7%, respectively) and mean length of stay was longer (4.6 vs. 3.7 days per patient per month, respectively). CONCLUSIONS: This retrospective analysis of patients with PTCL revealed high levels of comorbidity and HRU; novel interventions that improve patient outcomes and reduce the HRU burden of PTCL are needed.

Burden of illness among Medicare and non-Medicare US populations with acquired thrombotic thrombocytopenic purpura.

BACKGROUND: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare hematologic disorder that can lead to serious life-threatening medical complications. OBJECTIVE: The aim of this study was to describe aTTP-related hospital resource utilization, cost, complications, and overall survival among US Medicare and non-Medicare populations following aTTP episodes prior to the US approval of caplacizumab. METHODS: This retrospective study utilized administrative claims data for Medicare Fee-for-Service (FFS) beneficiaries (100% sample) and a sample of commercial, managed Medicaid [MM], Medicare Advantage [MA] plan members from the Inovalon MORE2 Registry. aTTP patients ages 18+ were identified between 2010 and 2018 using a published validated algorithm: ≥1 hospitalization for thrombotic microangiopathy + therapeutic plasma exchange (TPE). 2,279 patients were identified; 65.2% were enrolled in Medicare FFS, 13.6% in commercial, 15.7% in MM, and 5.4% in MA. Mean hospitalization days for aTTP index episode ranged between 12 and 17 days; ∼60% of patients required intensive care. Mean payments for index hospitalization varied by payer [Medicare FFS: $29,024; MA: $12,860; commercial: $9,996 and MM: $10,470]. Among FFS patients, 15.7% died during initial hospitalization and 21.0% died within first 30 days of the event. During follow-up, 11.6-19.6% experienced aTTP-related exacerbation. Incidence rate of relapse and complications per 100 person-years was 5.6 [Medicare FFS: 3.6; MA: 8.7; commercial: 10.4 and MM: 14.7] and 16.7 [FFS: 15.5; MA: 20.5; commercial: 21.7 and MM: 19.1], respectively. Among Medicare patients with and without aTTP, mortality risk was 2.9 (95 % CI: 2.4-3.4) times higher for aTTP vs. non-aTTP patients. CONCLUSION: This is the first real-world study evaluating burden of illness among aTTP patients in the US across payer types. Despite being treated with TPE, patients with aTTP have lower survival rates in comparison to a matched cohort without aTTP. These findings highlight the need for more effective and novel therapies to reduce disease burden for this population.Key pointsIn US Medicare and managed care populations with aTTP between 2010 and 2018, aTTP can lead to significant utilization of ICU services due to clinical complications, and/or relapse following hospital discharge.Despite treatment with therapeutic plasma exchange, acute mortality remains high (15.7%) indicating the need for more effective and novel treatments.

Risk and cost of infection-related hospitalizations in medicare beneficiaries with comorbid rheumatoid arthritis treated with abatacept versus other targeted disease-modifying anti-rheumatic drugs.

OBJECTIVE: This study evaluated infection-related hospitalization risk and cost in tumor necrosis factor inhibitor (TNFi)-experienced and targeted DMARD (tDMARD) naïve rheumatoid arthritis (RA) patients that were treated with abatacept, TNFi, or other non-TNFi. METHODS: This retrospective study used 100% Medicare Fee-for-Service claims to identify patients ≥65 age, diagnosed with RA, and were either 1) TNFi-experienced, who switched from a TNFi to another tDMARD (subsequent tDMARD claim served as index), or 2) tDMARD naïve (first therapy claim served as index), who initiated either abatacept, TNFi, or non-TNFi as their first tDMARD, between 2010 and 2017. Follow-up ended at the date of disenrollment, death, end of study period, or end of index treatment, whichever occurred first. Infection-related hospitalizations included pneumonia, bacterial respiratory, sepsis, skin and soft tissue, joint or genitourinary infections. A Cox proportional hazard model and two part generalized linear model were developed to estimate adjusted infection-related hospitalization risk and costs. Costs were normalized to per-patient-per-month (PPPM) and inflated to 2019 US$. RESULTS: The infection-related hospitalizations rate was lower during follow-up than during baseline periods for abatacept users, but was reversed for both TNFi and other non-TNFi users in both TNFi-experience and tDMARD naïve (p value < .001 based on Breslow-Day test for homogeneity of odds ratios). Infection-related hospitalization PPPM cost was significantly lower in abatacept treated patients compared to TNFi (TNFi-experienced: by $74; tDMARD naïve: $42) and other non-TNFi (TNFi-experienced: by $68; tDMARD naïve: $60). The adjusted infection-related hospitalization risk was significantly higher for RA patients treated with TNFi (TNFi-experienced HR: 1.48; 95% CI: 1.26-1.75, p < .0001; tDMARD naïve HR:1.59; 95% CI: 1.43-1.77, p < .0001) and other non-TNFi (TNFi-experienced HR:1.46; CI:1.28-1.66; tDMARD naïve HR:1.63; 95% CI: 1.44-1.83) than with abatacept. CONCLUSION: RA Medicare Fee-For-Service beneficiaries who either switched or initiated abatacept have a lower infection-related hospitalization risk and cost compared to patients who switched to or initiated other tDMARDs.

Health Care Resource Utilization and Costs Among Medicare Beneficiaries Newly Diagnosed With Peripheral T-cell Lymphoma: A Retrospective Claims Analysis.

BACKGROUND: There are limited data on the treatment patterns, health care resource utilization (HRU), survival outcomes, and medical costs among Medicare beneficiaries newly diagnosed with peripheral T-cell lymphoma (PTCL). PATIENTS AND METHODS: This was a retrospective analysis of data from the Medicare Fee-For-Service claims database using the 100% sample of the Medicare research identifiable files. Patients identified for analysis were aged ≥ 65 years and had received a PTCL diagnosis between January 2011 and December 2017. Outcomes included patient characteristics, HRU, direct all-cause and PTCL-specific health care costs, treatment patterns, and overall survival. Patients were followed until disenrollment, death, or end of the study period. RESULTS: Overall, 2551 patients with PTCL were included, among whom 37% had ≥ 1 emergency department visit and 42% had ≥ 1 hospitalization during the pre-index period. During follow-up (median, 2.0 years), 70% of patients were hospitalized at least once (mean length of stay, 1.34 days); 22% advanced to hospice care. A total of 1593 patients received ≥ 1 identifiable treatment regimen post index, of whom 26% received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and 3% CHOEP (CHOP plus etoposide), whereas 71% received other regimens. The median overall survival among patients receiving identifiable therapy was 4.6 years. The mean adjusted per-person-per-month all-cause costs among the overall PTCL cohort during follow-up were $5930; the mean disease-related costs were $2384. Costs were driven primarily by hospitalizations (38%) and outpatient services (28%). CONCLUSIONS: Medicare beneficiaries newly diagnosed with PTCL have high HRU and cost burden, with no evident standard of care in real-world practice.

Real-world burden of illness and unmet need in locally advanced or metastatic urothelial carcinoma following discontinuation of PD-1/L1 inhibitor therapy: A Medicare claims database analysis.

BACKGROUND: Several programmed death-1 or death-ligand 1 (PD-1/L1) inhibitors are approved first- or second-line therapies for locally advanced or metastatic urothelial carcinoma (la/mUC); however, clinical trials show that only ∼20% of patients respond and all ultimately progress. This study elucidated real-world treatment patterns, healthcare resource utilization (HRU), and economic burden among Medicare beneficiaries with la/mUC who discontinue PD-1/L1 inhibitor therapies. METHODS: We conducted a retrospective claims analysis of patients aged ≥65 years diagnosed with la/mUC (2015-2017) who initiated and subsequently discontinued PD-1/L1 inhibitor therapy (index=date of last administration) using Medicare Fee-for-Service Research Identifiable Files. Included patients had ≥12 months pre- and ≥3 months post-index continuous Medicare enrollment, and were followed until disenrollment, death, or data cutoff. RESULTS: Among 28,063 patients, 17% (n=4652) received ≥1 PD-1/L1 inhibitor following la/mUC diagnosis. Of these, 791 discontinued PD-1/L1 inhibitor therapy and met inclusion criteria (study cohort); 73% male, median age 76 years. Post-discontinuation, 3% received a different PD-1/L1 inhibitor, 46% chemotherapy, and 51% no further systemic treatment. HRU was high during follow-up: 97% had ≥1 outpatient visit and 52% ≥1 hospitalization. Healthcare costs per-patient-per-month were $7153 pre- and $7745 (adjusted) post-index; systemic therapy costs were higher pre- vs. post-index ($2978 vs. $1195) but other costs were higher post-index: hospitalization ($1120 vs. $2200), outpatient ($1437 vs. $2064), hospice ($3 vs. $536), skilled nursing facility ($106 vs. $384). CONCLUSIONS: Over half of Medicare beneficiaries with la/mUC received no disease-directed therapy post-PD-1/L1 inhibitor treatment. Patients who discontinued PD-1/L1 inhibitor therapy had intensive HRU unrelated to therapy costs, highlighting the significant burden of la/mUC and need for treatments that extend survival.