Association of Morbid Progression With Overall Survival Among Patients With Multiple Myeloma: Validation of the Progression-free Survival Endpoint.

INTRODUCTION: Multiple myeloma (MM) is an incurable malignancy, marked by end-organ damage that is frequently irreversible. Progressive disease (PD) can be defined as morbid PD, associated with new-onset hypercalcemia, renal insufficiency, anemia, or lytic bone lesions (CRAB symptoms), or as asymptomatic biochemical progression. The frequency of morbid versus asymptomatic PD and its effect on survival is unknown. Our aim was to determine the incidence of morbid PD, and to evaluate if this influences survival. PATIENTS AND METHODS: Data from 2 phase III trials of transplant-ineligible patients with newly diagnosed MM were included in a post hoc analysis. RESULTS: Of 2082 patients enrolled, 1243 (59.7%) experienced PD. At first progression, 543 (43.7%) patients had morbid PD; 12 (2.2%) had hypercalcemia, 271 (49.9%) had renal insufficiency, 370 (68.1%) developed anemia, and 79 (14.5%) developed new or enlarged bone lesions. A total of 700 (56.3%) patients had asymptomatic PD. Patients with morbid PD had worse second progression-free survival (PFS) versus patients with asymptomatic biochemical PD (median second PFS, 11.5 months vs. 20.0 months; hazard ratio, 1.63; 95% confidence interval, 1.43-1.85; P < .0001) and worse overall survival (OS) (median OS, 23.2 months vs 39.3 months; hazard ratio, 1.51; 95% confidence interval, 1.30, 1.74; P < .0001). CONCLUSIONS: Morbid PD occurs frequently and is associated with inferior second PFS and OS. As CRAB symptoms may not reverse with therapy, morbid PD is a meaningful event, and its association with a shortened PFS adds validity to PFS as a relevant endpoint in patients with MM.

Real-world treatment patterns, healthcare use and costs in triple-class exposed relapsed and refractory multiple myeloma patients in the USA.

Aim: To estimate treatment patterns and healthcare costs among triple-class exposed relapsed and refractory multiple myeloma (RRMM) patients. Materials & methods: Eligible patients had ≥1 line of therapy (LOT) each of proteasome inhibitors, immunomodulatory drugs and daratumumab in December 2015-September 2018 and received a new LOT. Results: A total of 154 patients were included with a median follow-up of 6.2 months. Median time from diagnosis to new LOT was 41.0 months. Kaplan-Meier estimate of median time to therapy discontinuation was 4.2 months. Mean per-patient, per-month MM-related costs were USD 35,657. Most frequently observed regimens were lenalidomide or pomalidomide + daratumumab (18.2%), lenalidomide or pomalidomide + proteasome inhibitors (15.6%) and lenalidomide or pomalidomide monotherapy (11.0%). Conclusion: Triple-class exposed RRMM patients receive heterogeneous treatments for a short duration with high healthcare resource utilization and costs.

Lenalidomide maintenance post-transplantation in newly diagnosed multiple myeloma: real-world outcomes and costs.

Aim: To compare real-world outcomes and costs among patients with newly diagnosed multiple myeloma receiving lenalidomide-only maintenance (Len-Mt) versus no maintenance after autologous hematopoietic stem cell transplantation. Patients & methods: Time to next treatment (TTNT) was evaluated; costs were calculated for 0-12, 12-24 and 24-36 months postindex date. Results: Len-Mt cohort had longer TTNT (HR: 0.43; p < 0.0001). Per-patient per-month costs during months 0-12 were higher among patients, receiving Len-Mt (USD 13,095 vs USD 8910; p < 0.0001), due to higher pharmacy costs - outpatient costs were lower. During months 12-24 and 24-36, outpatient costs were similar in both cohorts; total and pharmacy costs remained elevated for patients receiving Len-Mt. Conclusion: Len-Mt improved TTNT, initially reduced outpatient costs, but resulted in higher overall and pharmacy costs.

Racial disparities in treatment patterns and outcomes among patients with multiple myeloma: a SEER-Medicare analysis.

The objective of the study was to assess racial disparities in the treatment and outcomes among white, African American, and Hispanic patients with multiple myeloma (MM). Patients with an MM diagnosis from the Surveillance Epidemiology and End Results (SEER)-Medicare (2007-2013) database were included. Continuous Medicare enrollment for 6 months before (baseline) and after MM diagnosis was required unless death occurred. Time from MM diagnosis to novel therapy initiation and autologous stem cell transplant (ASCT), overall survival (OS), and MM-specific survival (MSS) was evaluated. Unadjusted and multivariable regressions compared African Americans and Hispanics vs whites. Trends of novel therapy and ASCT use across MM diagnosis years were assessed using linear regression models. The study included 3504 whites, 858 African Americans, and 468 Hispanics. African Americans and Hispanics had a longer time from MM diagnosis to novel therapy initiation vs whites (median: 5.2 and 4.6 vs 2.7 months, respectively). All cohorts had an increasing trend of novel therapy initiation within 6 months of MM diagnosis, particularly whites (all P < .05). Median MSS was significantly longer for African Americans (5.4 years) than whites (4.5 years; P < .05), and was comparable for Hispanics and whites. Median OS was similar overall (2.6-2.8 years). ASCT rate within 1 year of MM diagnosis rose among whites and African Americans (P < .05), but not Hispanics, who were less likely to receive ASCT vs whites. Significant variations in novel therapy and ASCT use were observed among different racial/ethnic groups with MM. Although OS was similar, both African Americans and Hispanics may not be fully benefitting from the introduction of novel therapies, as they receive them later than whites.

Treatment Patterns and Clinical and Economic Outcomes in Patients With Newly Diagnosed Multiple Myeloma Treated With Lenalidomide- and/or Bortezomib-containing Regimens Without Stem Cell Transplant in a Real-world Setting.

BACKGROUND: Real-world data in patients with newly diagnosed multiple myeloma (NDMM) are sparse. Using United States claims databases, we analyzed treatment patterns, clinical outcomes, and health care utilization and costs in patients receiving lenalidomide- and/or bortezomib-containing therapy. MATERIALS AND METHODS: Patient claims were obtained from a large commercial and Medicare database (October 2009 to May 2015). Patients with NDMM who received lenalidomide- and/or bortezomib-containing therapy and did not receive stem cell transplant (SCT) were analyzed. Duration of treatment (DOT), time to next treatment (TTNT), and health care utilization and costs were evaluated. RESULTS: Of 3075 patients, 1767 received doublet therapy (814 lenalidomide-dexamethasone [Rd], 953 bortezomib-dexamethasone [Vd]) and 464 received triplet therapy (318 lenalidomide-bortezomib-dexamethasone [RVd], 146 cyclophosphamide-bortezomib-dexamethasone [CyBord]). Rd versus Vd resulted in longer median DOT (12.0 vs. 5.9 months; P < .0001) and median TTNT (36.7 vs. 24.4 months; P = .0005). Year 1 costs were greater with Rd versus Vd (Δ = $14,964; P = .0009), primarily owing to higher pharmacy costs; outpatient physician visits and chemotherapy administration costs were lower. Median DOT (14.8 vs. 9.0 months; P < .0001) and median TTNT (35.7 vs. 22.3 months; P = .0007) were longer with RVd versus CyBord; year 1 costs were comparable. CONCLUSIONS: In this study of patients with NDMM ineligible for transplant, the median duration of therapy was approximately 70% of that in clinical trial observations. Lenalidomide therapy versus Vd and CyBord resulted in longer DOT, which correlated with longer TTNT, and higher pharmacy costs, which were partially offset by lower outpatient and chemotherapy administration costs.

Treatment Outcomes and Health Care Resource Utilization in Patients With Newly Diagnosed Multiple Myeloma Receiving Lenalidomide-only Maintenance, Any Maintenance, or No Maintenance: Results from the Connect MM Registry.

PURPOSE: Maintenance therapy after autologous stem cell transplantation (ASCT) improves clinical outcomes in multiple myeloma (MM), but the effect of continued treatment with lenalidomide-only maintenance, or any maintenance, on health care resource utilization (HCRU) is largely unknown. METHODS: Here we present an analysis of HCRU and clinical outcomes in a cohort of patients from the Connect MM registry, the largest, ongoing, observational, prospective US registry of patients with symptomatic newly diagnosed MM. In this study, patients with newly diagnosed MM who completed induction and single ASCT without subsequent consolidation received lenalidomide-only maintenance (n = 180), any maintenance (n = 256), or no maintenance (n = 165). HCRU (hospitalization, surgery/procedures, and concurrent medications [growth factors, bisphosphonates, or neuropathic pain medication]) was assessed starting from 100 days post-ASCT for up to 2 years. FINDINGS: Although the rates of hospitalization per 100 person-years were similar across groups at the end of years 1 and 2, the median duration of hospitalization was numerically longer with no maintenance. The rates of use of growth factors, bisphosphonates, and neuropathic pain medication were generally similar in all 3 groups. The receipt of any maintenance was associated with significantly reduced use of neuropathic pain medications during year 1. Of note, lenalidomide-only maintenance was associated with significantly longer progression-free survival (54.5 vs 30.4 months; hazard ratio [HR] = 0.58; 95% CI, 0.43-0.79; P = 0.0005) and overall survival (OS) (median OS not reached in either group; HR = 0.45; 95% CI, 0.28-0.73; P = 0.001) compared with no maintenance. Likewise, the group treated with any maintenance had significantly longer median progression-free survival (44.7 vs 30.4 months; HR = 0.62; 95% CI, 0.47-0.82; P = 0.0008) and OS (median OS not reached in either group; HR = 0.50; 95% CI, 0.33-0.76; P = 0.001) than did the group that did not receive maintenance. IMPLICATIONS: These findings suggest that in this largely community-based study population, post-ASCT maintenance therapy, including lenalidomide-only maintenance, improves clinical outcomes without negatively affecting HCRU. ClinicalTrials.gov identifier: NCT01081028.

Assessing the Effect of Adherence on Patient-reported Outcomes and Out of Pocket Costs Among Patients With Multiple Myeloma.

BACKGROUND: The present study characterized the effect of multiple myeloma (MM) on work productivity, health care resource usage, and out of pocket costs (OOPCs) and examined the association of adherence with quality of life (QoL) and productivity loss. MATERIALS AND METHODS: The present cross-sectional study included 162 patients categorized by their 4-item Morisky Medication Adherence Scale (MMAS-4) score (4 vs. ≤ 3). Online surveys included the Work Productivity and Activity Impairment questionnaire, Functional Assessment of Cancer Therapy-Multiple Myeloma (FACT-MM), and MM-specific questions. RESULTS: On average, patients reported FACT-MM scores of 98.5 ± 29.3, absenteeism of 18.3% ± 17.8%, presenteeism of 51.8% ± 30.2%, overall work productivity impairment of 57.3% ± 31.7%, and activity impairment of 49.9% ± 29.5% in the previous 7 days. During the previous 3 months, the mean OOPCs were $709 ± $1307; prescription medications accounted for 55% of these costs. Patients attended 4.1 ± 4.6 visits to oncologists or hematologists during that time, which accounted for 45% of the OOPCs. Patients spent an average of 6.8 ± 8.3 hours at MM-related monthly appointments, and 35.2% reported frustration while at the doctor's office. Patients with an MMAS-4 score of 4 reported higher FACT-MM scores (106.9 vs. 89.2; P < .001). Patients with an MMAS-4 score of ≤ 3 reported greater activity impairment (56.5% vs. 39.8%; P = .015) and feeling overwhelmed or frustrated with rescheduling MM appointments (64.0% vs. 26.0%; P = .002). CONCLUSION: MM was associated with significant workplace and functional impairment, high OOPCs, and frequent office visits. High medication adherence was associated with better outcomes across these domains. As survival for patients with MM improves, patient QoL should be considered to enhance these outcomes.

Cost-effectiveness of Pomalidomide, Carfilzomib, and Daratumumab for the Treatment of Patients with Heavily Pretreated Relapsed-refractory Multiple Myeloma in the United States.

PURPOSE: Pomalidomide plus low-dose dexamethasone (POM-d), daratumumab monotherapy (DARA), and carfilzomib monotherapy (CAR) have been approved for use in the treatment of patients with heavily pretreated relapsed-refractory multiple myeloma (RRMM) in the US, based on findings from the MM-002, SIRIUS, and PX-171-003-A1 studies, respectively. The objective of this study was to assess the cost-effectiveness of POM-d, DARA, and CAR in this patient population from a US payer's perspective. METHODS: A cost-effectiveness model was developed to estimate the cost and health outcomes over a 3-year time horizon in 3 health states: progression-free, post-progression, and death. The main efficacy data source was a matching-adjusted indirect comparison using data from the aforementioned studies. Direct medical costs were considered, including: treatment acquisition and administration (initial line and subsequent line), pre- and post-medication, prophylaxis treatment, adverse event management, and health care resource utilization. Sensitivity analyses were conducted. A scenario analysis that assumed equal efficacy across all 3 treatments was conducted. Costs, life-years, and quality-adjusted life-years were estimated and discounted at 3% per annum. FINDINGS: Over 3 years, the use of POM-d was associated with similar life-years and quality-adjusted life-years gained compared with DARA and CAR (incremental: life-years, +0.02 and +0.07, respectively; quality-adjusted life-years, +0.01 and +0.05), and with a cost less than that of DARA (-$8,919) and similar to that of CAR (-$195). Sensitivity analyses illustrated that the results were sensitive to progression-free survival, treatment duration, and drug costs. An equal efficacy scenario resulted in cost-savings relative to those of both DARA and CAR (-$11,779 and -$12,595). IMPLICATIONS: POM-d may be a cost-effective treatment option relative to DARA or CAR in heavily pretreated patients with RRMM in the US.

Real-World Treatment Patterns, Time to Next Treatment, and Economic Outcomes in Relapsed or Refractory Multiple Myeloma Patients Treated with Pomalidomide or Carfilzomib.

BACKGROUND: Negligible real-world evidence exists for later line treatment of multiple myeloma (MM) to assist treatment decisions or reimbursement models, such as episode-based payments. OBJECTIVE: To describe the treatment patterns and clinical/economic outcomes when pomalidomide or carfilzomib is used for relapsed/refractory MM. METHODS: A U.S. claims database was used to identify MM patients with an initial pomalidomide or carfilzomib claim (index date) between February 1, 2013, and February 28, 2015, which was assumed to be relapse therapy. Treatment regimens were defined as all MM chemotherapy observed within 60 days of index. Patients receiving pomalidomide and carfilzomib within 60 days of index were excluded. Time to next treatment (TTNT), a progression proxy, was defined as the addition of a new agent > 60 days from index or as treatment restart following a > 90-day therapy gap. Cost estimations used plan-allowed amounts. Descriptive statistics were used to compare outcomes between treatment groups, and regression models were used to adjust for baseline patient characteristics. RESULTS: There were 454 patients initiating treatment with pomalidomide (n = 264) or carfilzomib (n = 190) during the index period. The most frequent initial regimens for pomalidomide patients included pomalidomide + dexamethasone (47.0%) and pomalidomide alone (33.0%); the most frequent regimens for carfilzomib patients were carfilzomib alone (45.3%) and carfilzomib + dexamethasone (14.7%). The most frequent next line treatment for pomalidomide patients who progressed was the addition of (14.0%) or switch to (15.0%) carfilzomib ± dexamethasone and for carfilzomib patients, the most frequent next line treatment was pomalidomide + dexamethasone (9.3%) and carfilzomib alone or carfilzomib + dexamethasone + cyclophosphamide (6.7% each). The median (95% CI) TTNT for pomalidomide patients was 11.9 (10.7-14.8) compared with 9.4 (7.7-10.0) months for carfilzomib (P = 0.060). For patients followed to progression (pomalidomide: n = 100, 37.9%; carfilzomib: n = 75, 39.5%), mean TTNT was longer for patients initiating therapy with pomalidomide (6.9 months) versus carfilzomib (5.3 months, P = 0.016). When adjusted for baseline confounders, pomalidomide patients had a nonsignificant longer time to a subsequent treatment line. Inpatient encounters observed during the index line were very low (mean = 1) for both groups; outpatient encounters were fewer in pomalidomide patients. Adjusted analyses revealed inpatient encounters were higher (P = 0.005), while outpatient use was lower in pomalidomide patients (P = 0.006). Unadjusted median costs incurred during the initial line were similar between the 2 groups (pomalidomide: $102,805; carfilzomib: $127,203; P = 0.110) but significantly lower in pomalidomide patients after adjusting for baseline characteristics (P = 0.013). Unadjusted per patient per month (PPPM) costs incurred over the entire follow-up period were lower in pomalidomide-initiated patients ($18,298 vs. $24,734, P = 0.001) but not statistically significant in adjusted analyses (P = 0.230). CONCLUSIONS: A longer time to a subsequent line of therapy was observed in pomalidomide patients compared with carfilzomib patients, although the difference lost significance in adjusted analyses. Compared with carfilzomib, pomalidomide patients were observed to have lower unadjusted median PPPM costs over the entire post-index period and lower adjusted mean monthly costs during initial therapy. DISCLOSURES: Funding for this study was provided by Celgene. Chen, McGuiness, and Wade are employees of QuintilesIMS, which was contracted by Celgene to undertake this research. McGuiness also owns stock in Pfizer. Parikh, Abouzaid, Purnomo, and Hussein are employees of Celgene and participated fully in the development and approval of the manuscript. Portions of the results of this research were previously presented at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting; June 3-7, 2016; Chicago, Illinois. Study concept and design were contributed by Chen, Parikh, Abouzaid, McGuiness, and Wade. Chen and McGuiness took the lead in data collection, along with Wade, and data interpretation was performed by Hussein and Wade, with assistance from the other authors. The manuscript was written by McGuiness, Chen, and Wade, with assistance from Parikh and Abouzaid, and revised by McGuiness and Hussein, along with the other authors.

Identifying patient subgroups who benefit most from a treatment: using administrative claims data to uncover treatment heterogeneity.

OBJECTIVES: To illustrate how claims data can be used to (1) develop outcome scores that predict response to a traditional treatment and (2) estimate the economic impact of individualized assignment to a newer treatment based on the outcome score. An example application is based on two treatments for attention deficit hyperactivity disorder (ADHD): osmotic-release oral system methylphenidate (OROS-MPH) and lisdexamfetamine dimesylate (LDX). METHODS: Adolescents with ADHD initiating OROS-MPH (n=6320) or LDX (n=6394) were selected from the MarketScan claims database. A model was developed for predicting risk of switching/augmentation with OROS-MPH using multiple baseline characteristics. The model was applied to an independent sample to stratify patients by their predicted risk and, within each stratum, risk of switching/augmentation and ADHD-related total costs were compared between OROS-MPH and LDX patients using inverse probability of treatment weighting. RESULTS: The prediction model resulted in substantial stratification, showing risk of switching/augmentation with OROS-MPH ranging from 11.3-42.1%. In the two strata where OROS-MPH had highest risk of switching/augmentation, LDX had significantly lower risk of switching/augmentation than OROS-MPH (by 7.0-8.2%) and lower ADHD-related annual total costs (by $264-$625 per patient). LIMITATIONS: The current study has used the risk of switching/augmentation as a proxy measure for treatment efficacy to establish the prediction model. Future research using a clinical measure for ADHD symptoms is warranted to verify the findings. CONCLUSIONS: Combining multiple patient characteristics into a predicted score for treatment outcomes with a traditional treatment can help identify subgroups of patients who benefit most from a new treatment. In this analysis, ADHD patients with a high predicted score for switching/augmentation with OROS-MPH had a lower rate of switching/augmentation with LDX. Assigning OROS-MPH and LDX treatments based on the predicted scores that are heterogeneous in a patient population may help improve clinical outcomes and the cost-effectiveness of care.

Economic evaluation of denosumab compared with zoledronic acid in hormone-refractory prostate cancer patients with bone metastases.

BACKGROUND: Bone metastases are common in patients with hormone-refractory prostate cancer. In a study of autopsies of patients with prostate cancer, 65%-75% had bone metastases. Bone metastases place a substantial economic burden on payers with estimated total annual costs of $1.9 billion in the United States. Skeletal-related events (SREs), including pathologic fractures, spinal cord compression, surgery to bone, and radiation to bone, affect approximately 50% of patients with bone metastases. They are associated with a decreased quality of life and increased health care costs. Zoledronic acid is an effective treatment in preventing SREs in solid tumors and multiple myeloma. Recently, denosumab was FDA-approved for prevention of SREs in patients with bone metastases from solid tumors. A Phase 3 clinical trial (NCT00321620) demonstrated that denosumab had superior efficacy in delaying first and subsequent SREs compared with zoledronic acid. However, the economic value of denosumab has not been assessed in patients with hormone-refractory prostate cancer. OBJECTIVE: To compare the cost-effectiveness of denosumab with zoledronic acid in the treatment of bone metastases in men with hormone-refractory prostate cancer. METHODS: An Excel-based Markov model was developed to assess costs and effectiveness associated with the 2 treatments over a 1- and 3-year time horizon. Because the evaluation was conducted from the perspective of a U.S. third-party payer, only direct costs were included. Consistent with the primary outcome in the Phase 3 trial, effectiveness was assessed based on the number of SREs. The model consisted of 9 health states defined by SRE occurrence, SRE history, disease progression, and death. A hypothetical cohort of patients with hormone-refractory prostate cancer received either denosumab 120 mg or zoledronic acid 4 mg at the model entry and transitioned among the 9 health states at the beginning of each 13-week cycle. Transition probabilities associated with experiencing the first SRE, subsequent SREs, disease progression, and death were primarily derived from the results of the Phase 3 clinical trial and were supplemented with published literature. The model assumed that a maximum of 1 SRE could occur in each cycle. Drug costs included wholesale acquisition cost, health care professional costs associated with drug administration, and drug monitoring costs, if applicable. Nondrug costs included incremental costs associated with disease progression, costs associated with SREs, and terminal care costs, which were derived from the literature. Adverse event (AE) costs were estimated based on the incidence rates reported in the Phase 3 trial. Resource utilization associated with AEs was estimated based on consultation with a senior medical director employed by the study sponsor. All costs were presented in 2010 dollars. The base case estimated the incremental total cost per SRE avoided over a 1-year time horizon. Results for a 3-year time horizon were also estimated. One-way sensitivity analyses and probabilistic sensitivity analyses (PSA) were performed to test the robustness of the model. RESULTS: In the base case, the total per patient costs incurred over 1 year were estimated at $35,341 ($19,230 drug costs and $16,111 nondrug costs) for denosumab and $27,528 ($10,960 drug costs and $16,569 nondrug costs) for zoledronic acid, with an incremental total direct cost of $7,813 for denosumab. The estimated numbers of SREs per patient during the 1-year period were 0.49 for denosumab and 0.60 for zoledronic acid, resulting in an incremental number of SREs of -0.11 in the denosumab arm. The estimated incremental total direct costs per SRE avoided with the use of denosumab instead of zoledronic acid were $71,027 for 1 year and $51,319 for 3 years. The 1-way sensitivity analysis indicated that the results were sensitive to the drug costs, median time to first SRE, and increased risk of SRE associated with disease progression. Results of the PSA showed that based on willingness-to-pay thresholds of $70,000, $50,000, and $30,000 per SRE avoided, respectively, denosumab was cost-effective compared with zoledronic acid in 49.5%, 17.5%, and 0.3% of the cases at 1 year, respectively, and 79.0%, 49.8%, and 4.1% of the cases at 3 years, respectively. CONCLUSIONS: Although denosumab has demonstrated benefits over zoledronic acid in preventing or delaying SREs in a Phase 3 trial, it may be a costly alternative to zoledronic acid from a U.S. payer perspective.

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.

Economic consequence of switching to citalopram after its generic entry for adult patients with major depressive disorder (MDD) treated with escitalopram: a 6-month retrospective study.

OBJECTIVE: To estimate, from a third-party payer's perspective, the effects of switching from escitalopram to citalopram, after the generic entry of citalopram, on hospitalization and healthcare costs among adult MDD patients who were on escitalopram therapy. METHODS: Adult MDD patients treated with escitalopram were identified from Ingenix Impact claims database. MDD- and mental health (MH)-related hospitalization rates and healthcare costs were compared between 'switchers' (patients who switched to citalopram after its generic entry) and 'non-switchers'. MDD- and MH-related outcomes were defined as having a primary or a secondary diagnosis of ICD-9-CM = 296.2x, 296.3x and ICD-9-CM = 290-319, respectively. A propensity score matching method that estimated the likelihood of switching using baseline characteristics was used. Outcomes were examined for both 3-month and 6-month post-index periods. RESULTS: The sample included 3,427 matched pairs with balanced baseline characteristics. Switchers were more likely to incur an MDD-related (odds ratio [OR] = 1.52) and MH-related hospitalization (OR = 1.34) during the 6-month post-index period (both p < 0.05). Compared to switchers, non-switchers had significantly lower MDD- and MH-related hospitalization costs ($248.3 and $219.8 lower, respectively) and medical costs ($277.4 and $246.4 lower, respectively) (all p < 0.05). Although non-switchers had significantly higher MDD- and MH-related prescription drug costs, overall they had significantly lower total MDD- and MH-related healthcare costs ($109.9 and $93.6 lower, respectively; both p < 0.001). The 3-month results were consistent with these 6-month findings. LIMITATIONS: The study limitations included limited generalizability of study findings, inability to differentiate switching from escitalopram to citalopram due to medical reasons versus non-medical reasons, and exclusion of indirect costs from cost calculations. CONCLUSIONS: Compared to patients maintaining on escitalopram, switchers from escitalopram to citalopram experienced higher risk of MDD- and MH-related hospitalization and incurred higher total MDD- and MH-related healthcare costs. The economic consequences of therapeutic substitution should take into account total healthcare costs, not just drug acquisition costs.