Adjusted Indirect Treatment Comparison of Progression-Free Survival with D-Rd and VRd Based on MAIA and SWOG S0777 Individual Patient-Level Data.

INTRODUCTION: Daratumumab plus lenalidomide and dexamethasone (D-Rd) and bortezomib plus lenalidomide and dexamethasone (VRd) are commonly used treatment combinations for transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). D-Rd and VRd demonstrated superior efficacy relative to lenalidomide and dexamethasone (Rd) in the MAIA and SWOG S0777 trials, respectively, but have not been compared directly in a head-to-head trial. Naïve comparisons of efficacy across the two trials may be biased because MAIA enrolled only TIE patients (median age 73 years), whereas SWOG S0777 enrolled both TIE patients and transplant-eligible patients who chose to defer/refuse frontline stem cell transplantation (median age 63 years). The present study compared progression-free survival (PFS) in TIE patients with NDMM treated with D-Rd versus VRd based on an adjusted indirect treatment comparison (ITC) that leveraged individual patient-level data from MAIA and SWOG S0777. METHODS: Harmonized inclusion/exclusion criteria (including age ≥ 65 years as a proxy for transplant ineligibility) and propensity-score weighting were used to balance the trial populations on measured baseline characteristics. After differences in trial populations were adjusted for, an anchored ITC was performed wherein within-trial PFS hazard ratios (HRs) for D-Rd versus Rd and VRd versus Rd were estimated and used to make indirect inference about PFS for D-Rd versus VRd. RESULTS: PFS HRs were 0.52 (95% confidence interval [CI] 0.41-0.67) for D-Rd versus Rd based on MAIA data, 0.88 (95% CI 0.63-1.23) for VRd versus Rd based on SWOG S0777 data, and 0.59 (95% CI 0.39-0.90) for the Rd-anchored ITC of D-Rd versus VRd. Sensitivity and subgroup analyses produced results consistent with the primary results. CONCLUSION: This anchored ITC demonstrated a greater PFS benefit for D-Rd versus VRd in TIE patients with NDMM. In the absence of head-to-head trials comparing D-Rd and VRd, the present trial may help inform treatment selection in this patient population.

Multiple drug combinations can be used to treat patients with newly diagnosed multiple myeloma (NDMM) who are not eligible for a stem cell transplant. Two of these combinations­daratumumab plus lenalidomide and dexamethasone (D-Rd) and bortezomib plus lenalidomide and dexamethasone (VRd)­have each been studied in clinical trials (MAIA and SWOG S0777) against the combination of lenalidomide plus dexamethasone (Rd), but D-Rd and VRd have not been compared directly in a head-to-head clinical trial. Our study used data from the MAIA and SWOG S0777 trials to indirectly compare outcomes observed with D-Rd and VRd. For this indirect comparison between D-Rd and VRd, we first made adjustments to the patient populations of each trial to make them more similar to each other; this helped to make sure any differences we saw in treatment outcomes between D-Rd and VRd would not be because of differences in the characteristics of the patients who participated in the trials. After we made these adjustments to the patient populations of each trial, both D-Rd and VRd lowered the risk of disease progression or death compared with Rd alone. However, when indirectly compared in our study, D-Rd lowered the risk of disease progression or death by 41% compared with VRd. As data directly comparing treatment outcomes for D-Rd and VRd are not available, this indirect comparison can contribute to the information used to make treatment decisions for patients with NDMM who are not eligible for a stem cell transplant.

Progression-Free Survival of Daratumumab Versus Bortezomib Triplet Combination With Lenalidomide and Dexamethasone in Transplant Ineligible Patients With Newly Diagnosed Multiple Myeloma: TAURUS Chart Review Study.

BACKGROUND: Daratumumab, lenalidomide and dexamethasone (DRd) and bortezomib, lenalidomide and dexamethasone (VRd) are preferred regimens for transplant ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). Both DRd and VRd demonstrated superior efficacy versus Rd in the MAIA and SWOG S0777 trials, respectively, but there is no head-to-head (H2H) clinical trial comparing their efficacy. Differing populations in the MAIA and S0777 trials make an unadjusted comparison of outcomes challenging and biased. The current TAURUS study is the first real-world H2H study comparing progression-free survival (PFS) among TIE NDMM patients treated with DRd or VRd as first-line (1L) in similar clinical settings. MATERIALS AND METHODS: A multicenter chart review study was conducted at nine sites across the United States. All TIE patients treated with DRd and a randomly selected population of VRd patients were included. TIE NDMM patients aged ≥65 were included if they initiated 1L DRd/VRd between January 2019 and September 2021. PFS was defined as the time from DRd/VRd initiation until disease progression or death. A doubly-robust multivariable Cox regression model combined with inverse probability of treatment weighting (IPTW) methodology was used to compare PFS between cohorts. RESULTS: Weighted cohorts comprised 91 DRd and 87 VRd patients. Thirteen DRd and 24 VRd patients experienced progression/death. Patients treated with DRd had a lower risk of progression/death versus VRd (adjusted hazard ratio: 0.35, 95% confidence interval: [0.17; 0.73]). CONCLUSION: DRd is associated with a significantly lower risk of disease progression or death compared to VRd as 1L treatment for TIE NDMM patients.

Racial disparities in utilization of first-generation versus second-generation long-acting injectable antipsychotics in Medicaid beneficiaries with schizophrenia.

BACKGROUND: Multiple studies report racial disparities in antipsychotic prescription patterns. This study assessed demographic and clinical factors associated with the utilization of first-generation (FG) versus second-generation (SG) long-acting injectable (LAI) antipsychotics. METHODS: This retrospective, observational cohort analysis used claims data from the IBM MarketScan® Multi-State Medicaid database. The study included adults with an LAI claim between 01-January-2009 and 31-December-2018, an ICD-9-CM or ICD-10-CM diagnosis of schizophrenia, race recorded as Black or White, and ≥12 months of continuous enrollment before the index LAI. Descriptive analysis detailed the relationship between race and FG or SG LAI initiation. Multivariate logistic regression was used to assess potential associations with FG vs. SG LAI initiation, including clinical and demographic factors, comorbidities, and index year. RESULTS: A total of 10,773 patients were included: 6659 (62 %) Black and 4114 (38 %) White. Black patients had a higher utilization of FG LAIs than White patients (46.8 % vs. 38.9 %) over the 10 years analyzed. Black patients were more likely to utilize FG LAIs than White patients (odds ratio: 1.47; 95 % CI: 1.34, 1.62) after controlling for index year and covariates (race, age, gender, insurance plan type, Quan-Charlson Comorbidity index score, comorbidities, prior medications). Significant predictors of FG LAI utilization were older age, type of baseline oral antipsychotic (FG vs SG), type of coverage (managed care vs fee for service), and greater comorbidity burden. CONCLUSION: The utilization of FG LAIs was greater in Black compared to White Medicaid beneficiaries with schizophrenia over a 10-year period. These findings suggest that racial disparities exist in LAI initiation, with implications for differential quality of schizophrenia treatment.

Real-world Duration of Use and Dosing Frequency of Daratumumab in Patients With Multiple Myeloma in the United States.

Daratumumab (DARA) is an anti-CD38 monoclonal antibody approved as a combination therapy for newly diagnosed multiple myeloma (MM) and as monotherapy and combination therapy for relapsed or refractory MM cases. We assessed the length of DARA use across lines of therapy and the probabilities of treatment discontinuation in patients with MM in the real-world. We used the deidentified Clinformatics Data Mart database from Optum to identify patients with MM (n=2124) who received DARA-containing treatment between November 1, 2015 and March 31, 2021 in the United States. Patients were excluded if they had received a stem cell transplant. The duration of DARA use was defined as the time interval between the first initiation and discontinuation of DARA as a time-to-event outcome using the Kaplan-Meier method. A gap of more than 60 days between 2 consequent DARA claim dates was defined as DARA discontinuation. The median duration of continuous DARA use was 16.6 months. By 24 months, 33.1% of patients remained on DARA treatment. In a subgroup analysis of patients with 12 months or more continuous insurance coverage (n=1246), the median length of DARA use was 24.7 months; by 24 months, 51.8% remained on DARA treatment. The dose adherence ratios (observed DARA doses relative to the label) were close to 1.0, particularly among patients with longer follow-up, indicating that real-world DARA dosing frequency was similar to that on the approved label. In summary, this real-world analysis reported that the median duration of continuous DARA use is 16.6 months, with high dosing adherence in patients who have MM.

Racial and Ethnic Disparities in Treatment Initiation Among Patients with Newly Diagnosed Psoriatic Arthritis: A Retrospective Medicaid Claims Database Study.

INTRODUCTION: In patients with psoriatic arthritis (PsA), potential differences in care by race/ethnicity have not been well studied. METHODS: This retrospective, observational cohort analysis utilized the IBM MarketScan® Multi-State Medicaid database. Patients aged ≥ 18 years with two or more PsA-related claims between January 1, 2010 and December 31, 2019, and ≥ 12 months of continuous enrollment before the first diagnosis of PsA (index date) were included. Outcomes evaluated were the use of disease-modifying antirheumatic drugs (DMARDs) overall and by type (conventional synthetic, biologic, targeted synthetic) within 12 months following initial PsA diagnosis, as well as the time to DMARD initiation after initial PsA diagnosis, stratified by race/ethnicity. Multivariate Cox proportional hazards models were used to assess potential associations between patient baseline characteristics and time to DMARD initiation. RESULTS: Among patients with newly diagnosed PsA (N = 3432), the mean age was 44.4 years, 69.9% were female, 77.4% were White, and 10.1% were Black. Of the 2993 patients with at least 12 months of follow-up, fewer Black patients received any DMARD therapy compared with White patients (68.4 vs. 76.4%, respectively, p = 0.002), and, specifically, a lower percentage of Black patients received biologic DMARDs compared with White patients (33.6 vs. 42.6%, respectively, p = 0.003). After adjusting for baseline characteristics, Black patients had significantly longer time to initiation of any DMARD (HR [95% CI] 0.82 [0.71-0.94]) and biologic DMARD (0.84 [0.71-0.99]) compared with White patients. Other baseline variables such as older age, anxiety, and hepatitis C were also significantly associated with longer time to any DMARD initiation after initial PsA diagnosis. CONCLUSIONS: Time to treatment initiation was significantly longer in Black patients compared with White patients with newly diagnosed PsA. These findings suggest care delivery disparities in patients with PsA and highlight the need for future studies to understand factors that drive the observed differences in drug therapy by race/ethnicity.

Real-world calibration and transportability of the Disease Recovery Evaluation and Modification (DREaM) randomized clinical trial in adult Medicaid beneficiaries with recent-onset schizophrenia.

BACKGROUND: The Disease Recovery Evaluation and Modification study (DREaM; NCT02431702) assessed the benefit of initiating paliperidone palmitate (PP), a long-acting injectable antipsychotic, in patients with recent-onset schizophrenia or schizophreniform disorder. OBJECTIVE: To determine whether reductions in psychiatric hospitalizations with early initiation of PP vs oral antipsychotic (OAP) therapy observed in a DREaM post hoc analysis are transportable to a real-world population of patients with recent-onset schizophrenia. METHODS: Patients enrolled in DREaM were randomized to receive OAP or PP for 9 months, after which OAP recipients were re-randomized to receive OAP or PP for another 9 months. We used this design to form treatment arms: OAP-OAP, OAP-PP, and PP-PP. Inclusion/exclusion criteria were used to identify a Medicaid Managed Care (MMC) OAP-treated cohort of 1,000 patients diagnosed with schizophrenia using IBM Truven databases from 2015 to 2019. The MMC cohort was combined with the subset of patients diagnosed with schizophrenia enrolled in DREaM from US sites (N = 45, 43, and 44 for OAP-OAP, OAP-PP, and PP-PP, respectively). Propensity scores for the MMC cohort were estimated using baseline variables identified via double-lasso regression. Estimated propensity scores were used to weight psychiatric hospitalizations in the DREaM OAP-OAP group and compared with observed MMC OAP cohort psychiatric hospitalizations. After the successful calibration of the DREaM OAP-OAP group, similar approaches were taken for the OAP-PP and PP-PP groups to transport DREaM effects to MMC data. RESULTS: Standardized mean differences in baseline covariates between DREaM treatment arms and MMC groups were substantially reduced after calibration. The 18-month cumulative numbers of psychiatric hospitalizations per patient (SE) were 0.83 (0.14) for the MMC cohort, 0.43 (0.14) for the unweighted OAP-OAP, and 0.80 (0.37) for the calibrated OAP-OAP. The difference between the calibrated OAP-OAP and MMC was not statistically significant (difference, 0.03 [95% CI = -0.67 to 0.81]), indicating successful calibration. The mean difference in 18-month cumulative psychiatric hospitalizations relative to the MMC cohort was -0.77 (95% CI = -1.08 to -0.47) for OAP-PP and -0.83 (95% CI = -1.15 to -0.60) for PP-PP. CONCLUSIONS: Our study demonstrates that results from the DREaM OAP-OAP group reflect psychiatric hospitalizations in a real-world population when calibrated using specific baseline characteristics. Transporting the DREaM effects, we find that using OAP-PP and PP-PP treatment strategies for patients with recent-onset schizophrenia in the MMC population could reduce psychiatric hospitalizations compared with the use of OAP. These findings, along with the potential reduction in associated costs, should be considered when assessing the value of PP formulations. DISCLOSURES: Dr Basu reports consulting fees through Salutis Consulting LLC related to this work. Dr Mavros is a former employee of the Janssen Pharmaceutical Companies of Johnson & Johnson, Inc, and holds stock in the company. Ms Benson, Dr Fu, Ms Patel, and Dr Brown are employees of Janssen Scientific Affairs, LLC, and hold stock in Johnson & Johnson. This research was funded by Janssen Scientific Affairs, LLC. The sponsor was involved in the study design; collection, analysis, and interpretation of data; and development and review of the manuscript. All authors had full access to the study data and take responsibility for data integrity and the accuracy of the analyses. All authors provided direction and comments on the manuscript, reviewed and approved the final version prior to submission, made the final decision about where to publish these data, and approved submission to this journal.

Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial.

BACKGROUND: Addition of temozolomide (TMZ) to radiotherapy (RT) improves overall survival (OS) in patients with glioblastoma (GBM), but previous studies suggest that patients with tumors harboring an unmethylated MGMT promoter derive minimal benefit. The aim of this open-label, phase III CheckMate 498 study was to evaluate the efficacy of nivolumab (NIVO) + RT compared with TMZ + RT in newly diagnosed GBM with unmethylated MGMT promoter. METHODS: Patients were randomized 1:1 to standard RT (60 Gy) + NIVO (240 mg every 2 weeks for eight cycles, then 480 mg every 4 weeks) or RT + TMZ (75 mg/m2 daily during RT and 150-200 mg/m2/day 5/28 days during maintenance). The primary endpoint was OS. RESULTS: A total of 560 patients were randomized, 280 to each arm. Median OS (mOS) was 13.4 months (95% CI, 12.6 to 14.3) with NIVO + RT and 14.9 months (95% CI, 13.3 to 16.1) with TMZ + RT (hazard ratio [HR], 1.31; 95% CI, 1.09 to 1.58; P = .0037). Median progression-free survival was 6.0 months (95% CI, 5.7 to 6.2) with NIVO + RT and 6.2 months (95% CI, 5.9 to 6.7) with TMZ + RT (HR, 1.38; 95% CI, 1.15 to 1.65). Response rates were 7.8% (9/116) with NIVO + RT and 7.2% (8/111) with TMZ + RT; grade 3/4 treatment-related adverse event (TRAE) rates were 21.9% and 25.1%, and any-grade serious TRAE rates were 17.3% and 7.6%, respectively. CONCLUSIONS: The study did not meet the primary endpoint of improved OS; TMZ + RT demonstrated a longer mOS than NIVO + RT. No new safety signals were detected with NIVO in this study. The difference between the study treatment arms is consistent with the use of TMZ + RT as the standard of care for GBM.ClinicalTrials.gov NCT02617589.

Hypomorphic and dominant-negative impact of truncated SOX9 dysregulates Hedgehog-Wnt signaling, causing campomelia.

Haploinsufficiency for SOX9, the master chondrogenesis transcription factor, can underlie campomelic dysplasia (CD), an autosomal dominant skeletal malformation syndrome, because heterozygous Sox9 null mice recapitulate the bent limb (campomelia) and some other phenotypes associated with CD. However, in vitro cell assays suggest haploinsufficiency may not apply for certain mutations, notably those that truncate the protein, but in these cases in vivo evidence is lacking and underlying mechanisms are unknown. Here, using conditional mouse mutants, we compared the impact of a heterozygous Sox9 null mutation (Sox9+/-) with the Sox9+/Y440X CD mutation that truncates the C-terminal transactivation domain but spares the DNA-binding domain. While some Sox9+/Y440X mice survived, all Sox9+/- mice died perinatally. However, the skeletal defects were more severe and IHH signaling in developing limb cartilage was significantly enhanced in Sox9+/Y440X compared with Sox9+/-. Activating Sox9Y440X specifically in the chondrocyte-osteoblast lineage caused milder campomelia, and revealed cell- and noncell autonomous mechanisms acting on chondrocyte differentiation and osteogenesis in the perichondrium. Transcriptome analyses of developing Sox9+/Y440X limbs revealed dysregulated expression of genes for the extracellular matrix, as well as changes consistent with aberrant WNT and HH signaling. SOX9Y440X failed to interact with ß-catenin and was unable to suppress transactivation of Ihh in cell-based assays. We propose enhanced HH signaling in the adjacent perichondrium induces asymmetrically localized excessive perichondrial osteogenesis resulting in campomelia. Our study implicates combined haploinsufficiency/hypomorphic and dominant-negative actions of SOX9Y440X, cell-autonomous and noncell autonomous mechanisms, and dysregulated WNT and HH signaling, as the cause of human campomelia.

Racial or ethnic differences on treatment adherence and persistence among patients with inflammatory bowel diseases initiated with biologic therapies.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic disease with the potential for significant morbidity in case of suboptimal treatment (e.g. low treatment adherence). In spite of immense research in IBD, literature on association of IBD with race/ethnicity is fragmented. In this study, we aimed to evaluate the association between race/ethnicity and treatment adherence and persistence among patients with Crohn's disease (CD) or ulcerative colitis (UC) initiated with biologic therapies. METHODS: This observational, retrospective study utilized the Optum Clinformatics (Optum) Extended Data Mart Socioeconomic Status (SES) database. Adult patients with ≥ 2 medical claims for CD or UC diagnosis, ≥ 1 medical or pharmacy claim for corresponding FDA-approved biologic therapy, and a ≥ 12-month pre-index (index date: date of the first biologic medical/pharmacy claim) continuous health plan enrollment were included. Treatment adherence was measured as the proportion of days covered of ≥ 80% and treatment persistence by the number of days from the index date to the biologics discontinuation date. Switching among biologics was allowed for both treatment adherence and treatment persistence. Multivariable regression analyses were performed to evaluate the association between race/ethnicity and treatment adherence/persistence. RESULTS: Among patients with CD (N = 1430) and UC (N = 1059) included, majority were White (CD: 80.3%, UC: 78.3%), followed by African Americans (AA; CD: 10.5%, UC: 9.7%). Among patients with CD, AA were significantly less likely to adhere to biologics (adjusted OR [95%CI]: 0.61 [0.38; 0.99]) and more likely to discontinue biologics earlier (adjusted HR [95%CI]: 1.52 [1.16; 2.0]) during the follow-up period compared to Whites, after adjusting for other patient sociodemographic and clinical characteristics. Among patients with UC, no significant differences in the treatment adherence/persistence were observed between different races/ethnicities. CONCLUSIONS: Patients with CD were found to display racial differences in the treatment adherence and persistence of biologics, with significantly lower adherence and earlier discontinuation in AA compared to Whites. Such differences were not observed in patients with UC. Future studies are warranted to understand the possible reasons for racial differences, particularly in patients with CD.

Patient characteristics associated with dose modifications for VRd among newly diagnosed multiple myeloma patients.

Aim: To evaluate among multiple myeloma (MM) patients, the proportions with first-line bortezomib/lenalidomide/dexamethasone (VRd) dose modifications and the associated baseline patient characteristics. Patients & methods: Adult MM patients treated with first-line VRd were selected from the Optum claims database. VRd dose modifications were defined based on lenalidomide dose. Results: Among 1497 MM patients, 33% received VRd lite and 22% VRd reduced. Compared with VRd regular, VRd lite usage was more likely to be associated with patients aged ≥75 years and female sex; VRd reduced usage was more likely to be associated with female sex and frailty. Conclusion: A large proportion of MM patients received VRd dose modifications in the real-world, which could potentially result in reduced effectiveness of VRd.

Real-world patient characteristics and treatment outcomes among nontransplanted multiple myeloma patients who received Bortezomib in combination with Lenalidomide and Dexamethasone as first line of therapy in the United States.

BACKGROUND: There is limited real-world evidence that describes patients with newly diagnosed multiple myeloma (NDMM) treated with the bortezomib, lenalidomide, and dexamethasone (VRd) triplet regimen. We evaluated patient characteristics and treatment outcomes among nontransplanted NDMM patients who received VRd as their first line of therapy (LOT) in US oncology practice settings. METHODS: This retrospective observational cohort study evaluated patients from the Flatiron MM Core Registry who received VRd as first LOT between November 1, 2015, and February 28, 2021. Progression-free survival (PFS) was analyzed using the Kaplan-Meier method. Associations between patient demographic and clinical characteristics and PFS were evaluated using a multivariable Cox proportional hazards model. RESULTS: A total of 2342 eligible patients with VRd as first LOT were identified (mean age, 67.0 years). Among all identified patients, 64.3% were ≥ 65 years of age, 25.5% were elderly (≥75 years), and 47.9% were frail. Among patients with available data, 21.2% had high-risk cytogenetics, and the majority had International Staging System (ISS) stage I/II disease (71.8%), and Eastern Cooperative Oncology Group performance status (ECOG PS) score 0/1 (81.2%). Median duration of therapy was 5.5 months. With median follow-up of 21.0 months, median PFS and time-to-next-treatment were 26.5 and 16.1 months, respectively. Higher risk of disease progression or death was seen in patients categorized as elderly (hazard ratio [HR] = 1.37; 95% confidence interval [CI]: 1.13-1.66 vs patients < 65 years), having high-risk cytogenetics (HR = 1.44; 95% CI: 1.19-1.75 vs standard risk), having ISS disease stages II and III (HR = 1.31; 95% CI: 1.06-1.63 and HR = 1.37; 95% CI: 1.10-1.70 versus stage I, respectively), and having worse ECOG PS score (≥2) (HR = 1.49; 95% CI: 1.22-1.81 versus functionally active patients). CONCLUSIONS: The majority of patients treated with VRd in this study were ≥ 65 years of age, were ISS stage I/II, had an ECOG PS score of 0/1, and had standard cytogenetic risk. Median PFS observed in real-world practice was notably shorter than that observed in the SWOG S0777 clinical trial. In nontransplanted patients treated with VRd as first LOT, a higher risk of disease progression or death was associated with older age, having high-risk cytogenetics, worse disease stage, and worse ECOG PS score.

Risk factors for recurrent venous thromboembolism: a real-world analysis.

This study was conducted in patients treated for initial venous thromboembolism (VTE) for approximately 6 months to enhance understanding of the risk factors to inform clinical decision-making about long-term anticoagulation therapy. This retrospective cohort study was conducted using a large administrative claims database in the United States. A Cox proportional hazards model was used to examine demographic and clinical characteristics associated with recurrent VTE. A total of 13 831 patients had an index VTE event, and recurrent VTE occurred in 844 (6.1%) of these patients over a median follow-up of 22.8 months. Baseline comorbidities of arrhythmia, congestive heart failure, and chronic kidney disease were significantly associated with recurrent VTE. During the period of anticoagulation treatment after the index VTE, use of antidepressants was associated with an increased risk of recurrent VTE, whereas use of antibiotics and major surgery were associated with a decreased risk. In the 6 months prior to index VTE, anti-inflammatory agents and major surgery were associated with a decreased risk of recurrent VTE. The type of index VTE was also significantly associated with recurrent VTE, with an increased risk observed in patients with pulmonary embolism (PE) alone or PE with deep vein thrombosis (DVT) versus DVT alone. This real-world analysis identified baseline comorbidities, medications, and index VTE type to be factors predictive of recurrent VTE among patients treated for index VTE for approximately 6 months. Consideration of these factors may assist in the identification of patients who may benefit from extended anticoagulant therapy.

Healthcare Costs of Multiple Myeloma Patients with Four or More Prior Lines of Therapy, Including Triple-Class Exposure in the United States.

INTRODUCTION: The treatment of multiple myeloma (MM) remains a challenge as patients eventually progress through several lines of therapy (LOTs), requiring use of multiple MM drug classes. In this retrospective US claims-database study, we examined the healthcare costs of patients with MM who received ≥ 4 prior LOTs, including triple-class exposure (TCE). METHODS: Adult patients with MM were selected from the IBM MarketScan Commercial and Medicare claims databases (1 January 2012-30 June 2021). Eligible patients were required to have received at least four prior LOTs, and TCE (i.e., received a proteasome inhibitor, immunomodulatory drug, and anti-CD38-targeted monoclonal antibody) after the first-observed diagnosis of MM. The index date was defined as the initiation date of the first subsequent LOT after meeting the eligibility criteria for the study, and this date had to be after 1 January 2017 to capture contemporary cost estimates. The primary outcome measurements were all-cause and MM-related healthcare costs after the index date. RESULTS: The study population included 68 patients with MM (63% men), with a mean age of 59.8 years. Mean duration from first-observed MM diagnosis until index date averaged 46.7 months. During a mean follow-up of 21.9 months, total all-cause healthcare costs averaged US$757,386 per patient (equivalent to US$34,610 per patient per month). MM-related healthcare costs (US$670,561 per patient) contributed on average 88.5% to the total all-cause healthcare costs; the majority (67.2%) of MM-related healthcare costs were attributed to drug and infusion costs (US$450,952 per patient). CONCLUSIONS: In this retrospective US claims-database study, patients with MM with ≥ 4 prior LOTs, including TCE, continued to experience high healthcare costs that were mostly attributable to anti-myeloma drugs and their administration.

Healthcare resource utilization and costs before and after long-acting injectable antipsychotic initiation in commercially insured young adults with schizophrenia.

BACKGROUND: Long-acting injectable (LAI) antipsychotics use is associated with improved adherence which can reduce the rate of relapse, hospitalization, and associated costs in patients with schizophrenia. Young adults could be at higher risk of poor adherence, hence use of LAI in this population may offer a benefit but the evidence is limited. This study aimed to compare clinical and economic outcomes before and after the initiation of LAI antipsychotics in commercially insured young adults (18-35 years of age) with schizophrenia. METHODS: A retrospective claims data study was conducted using the data from the IBM MarketScan® Commercial Claims and Encounters (CCAE) Database. Patients with a continuous enrollment of at least 1-year before and 1-year after the first observed schizophrenia diagnosis (index date) and with the use of ≥1 typical or atypical LAI antipsychotic during the post-index follow-up period were included. A pre-post analysis was conducted to compare relapse rates, healthcare resource utilization, and costs before (from index date to LAI initiation) and after LAI initiation (to end of follow up). RESULTS: A total of 2222 patients who initiated LAIs after an index schizophrenia diagnosis were identified. The per patient per month (PPPM) composite relapse event rate (0.109 pre-LAI to 0.073 post-LAI) and hospitalization rate (0.091 to 0.058), all-cause inpatient visits (0.231 to 0.119), and length of stay (2.694 to 1.092 days) significantly decreased from before LAI initiation to after LAI initiation with similar trends seen for mental health and schizophrenia-related measures (all significant; P < 0.0001). All-cause total costs ($4898 to $3078 PPPM) were also decreased after LAI initiation, with similar trends seen for mental health and schizophrenia-related costs (all significant; P < 0.0001). Although medication costs were higher post-LAI period ($311 to $542 PPPM), the cost increase was substantially offset by the decreased costs associated with total healthcare costs. CONCLUSIONS: Treatment with LAI antipsychotics was associated with a decrease in relapse event rate, healthcare resource utilization, and costs after LAI initiation compared to before LAI initiation in commercially insured young adults with schizophrenia. Treatment with LAIs in young adults with schizophrenia is potentially associated with significant cost savings to commercial payers.

Depression and food insecurity among patients with rheumatoid arthritis in NHANES.

BACKGROUND: Social determinants of health (SDH), including food insecurity, are associated with depression in the general population. This study estimated the prevalence of depression and food insecurity and evaluated the impact of food insecurity and other SDH on depression in adults with rheumatoid arthritis (RA). METHODS: Adults (≥ 18 years) with RA were identified from the 2013-2014 and 2015-2016 National Health and Nutrition Examination Survey (NHANES). Depression was defined as a score of ≥ 5 (mild depression: 5-9; moderate-to-severe depression: 10-27) using the Patient Health Questionnaire-9 (PHQ-9). Food insecurity was assessed with the 18-item US Household Food Security Survey Module. Adults with household-level marginal-to-very-low food security were classified as experiencing food insecurity. The prevalence of depression and food insecurity among participants with RA were estimated. Weighted logistic regression was used to evaluate the association between depression and participants' characteristics including SDH. Penalized regression was performed to select variables included in the final multivariable logistic regression. RESULTS: A total of 251 and 276 participants from the 2013-2014 and the 2015-2016 NHANES, respectively, had self-reported RA. The prevalence of depression among these participants was 37.1% in 2013-2014 and 44.1% in 2015-2016. The prevalence of food insecurity was 33.1% in 2013-2014 and 43.0% in 2015-2016. Food insecurity was associated with higher odds of having depression (OR 2.17, 95% CI 1.27, 3.72), and the association varied by depression severity. Compared with participants with full food security, the odds of having depression was particularly pronounced for those with very low food security (OR 2.96, 95% CI 1.48, 5.90) but was not significantly different for those with marginal or low food security. In the multivariable regression, being female, having fair/poor health condition, any physical disability, and ≥ 4 physical limitations were significantly associated with depression. CONCLUSIONS: In adults with self-reported RA, the prevalence of depression and food insecurity remained high from 2013 to 2016. We found that depression was associated with SDH such as food insecurity, although the association was not statistically significant once adjusted for behavioral/lifestyle characteristics. These results warrant further investigation into the relationship between depression and SDH among patients with RA.

Healthcare Costs Incurred by Patients with Multiple Myeloma Following Triple Class Exposure (TCE) in the US.

INTRODUCTION: Multiple myeloma (MM) is a malignancy of plasma cells; most MM patients will eventually relapse or become refractory to treatment. Treating MM patients remains a challenge since patients eventually progress through several lines of therapy (LOTs), requiring the use of multiple MM drug classes. We examined healthcare resource utilization (HCRU) and the costs incurred by MM patients following triple class exposure (TCE; defined as exposure to a proteosome inhibitor, an immunomodulatory agent, and an anti-CD-38 antibody). METHODS: Adult MM patients were selected from the MarketScan® commercial and Medicare supplemental databases (January 2009-February 2021). From this cohort, patients who had TCE and ≥ 1 subsequent LOT that occurred after January 1, 2017 were included in the study population. The initiation date for the first post-TCE LOT was defined as the index date. All-cause and MM-related HCRU and the associated costs were examined post-index date. RESULTS: A total of 85 MM patients with TCE who initiated ≥ 1 subsequent LOT post-TCE and had ≥ 1 year of follow-up post-index date were included in the study population; mean age on index date was 58.8 years, and 60.0% were male. The time from first-observed MM diagnosis until index date averaged 47.5 months. During an average follow-up of 20.9 months post-index date, 64.7% of patients (N = 55) initiated a second LOT and 35.2% (N = 30) received at least 3 LOTs. During follow-up, mean total all-cause healthcare cost per patient was $722,992 (equivalent to $34,578 per patient per month [PPPM]). Approximately 90.7% ($655,524 per patient) of the total all-cause healthcare costs were MM related, 66.0% of which were MM drug/infusion costs. CONCLUSION: In this real-world US study, MM patients with TCE incurred high healthcare costs, with the majority being MM related and primarily attributed to MM drug and infusion costs.

Postoperative, Single-Fraction Radiation Therapy in Merkel Cell Carcinoma of the Head and Neck.

PURPOSE: Conventionally fractionated, postoperative radiation therapy (cPORT; 50 Gy in 25 fractions) is considered for patients with Merkel cell carcinoma (MCC) to improve locoregional control. However, cPORT is associated with acute toxicity, especially in the head and neck (H&N) region, and requires daily treatments over several weeks. We previously reported high rates of durable local control with minimal toxicity using 8-Gy single-fraction radiation therapy (SFRT) in the metastatic setting. We report early results on a cohort of patients with localized H&N MCC who received postoperative SFRT if a cPORT regimen was not feasible. METHODS AND MATERIALS: Twelve patients with localized MCC of the H&N (clinical/pathologic stages I-II) and no prior radiation therapy to the region were identified from an institutional review board-approved prospective registry who underwent surgical resection followed by postoperative SFRT. Time to event was calculated starting from the date of resection before SFRT. The cumulative incidence of in-field locoregional recurrences and out-of-field recurrences was estimated with death as a competing risk. RESULTS: Twelve patients with H&N MCC were identified with clinical/pathologic stages I-II H&N MCC. Median age at diagnosis was 81 years (range, 58-96 years); 25% had immunosuppression. At a median follow-up of 19 months (range, 8-34), there were no in-field locoregional recurrences. A single out-of-field regional recurrence was observed, which was successfully salvaged. There were no MCC-specific deaths. No radiation-associated toxicities greater than grade 1 (Common Terminology Criteria for Adverse Events v5) were observed. CONCLUSIONS: Preliminary data suggest that SFRT could offer a potential alternative to cPORT to treat the primary site for localized H&N MCC, particularly in elderly or frail patients, with promising in-field local control and minimal toxicity. Further data with validation in larger cohorts are needed to confirm the sustained safety and efficacy of postoperative SFRT.

Distance to glycemic goal at the time of treatment intensification in patients with type 2 diabetes mellitus failing metformin monotherapy in the United States.

Background: A substantial proportion of patients with type 2 diabetes mellitus (T2DM) do not reach their target HbA1c level on metformin. The objective of this retrospective observational cohort study is to better characterize the distance between HbA1c target and patient's actual HbA1c level (the distance to goal), using a target HbA1c of 7.0% (53 mmol/mol), in patients with T2DM who have started metformin monotherapy.Methods: We used data from the GE Centricity Electronic Medical Record database by IQVIA in 2016 in the United States (US) to identify adults with T2DM who started metformin monotherapy (MM) and received at least 90 days of treatment. Patients were categorized into three groups: those who achieved the goal of HbA1c <7.0%, those who did not achieve the goal of HbA1c <7.0% (i.e. failed MM) and received intensified treatment, and those who failed MM and did not receive intensified treatment. Distance to goal was computed for patients in each group.Results: We identified 20,704 patients in the US database who started MM; 1741 (8.4%) failed MM and received intensified treatment, while 4977 (24.0%) failed MM and did not receive intensified treatment. The mean post-MM HbA1c for those who failed MM and received intensified treatment was 8.7% (72 mmol/mol) (median 8.2%, 66 mmol/mol) and the mean distance to goal was 1.7% (median 1.2%). The mean post-MM HbA1c for those who failed MM and did not receive intensified treatment was 8.0% (64 mmol/mol) (median 7.5%, 58 mmol/mol) and the mean distance to goal was 1.0% (median 0.5%).Conclusion: A proportion of US T2DM patients do not achieve glycemic control (target HbA1c < 7.0%) despite 90 days of MM. Patients who failed MM and eventually received intensified treatment did so when their HbA1c distance to goal exceeded the level at which one add-on therapy alone might be sufficient to bring them to goal.

Dose distribution and up-titration patterns of metformin monotherapy in patients with type 2 diabetes.

AIMS: To assess the dose distribution among users of metformin monotherapy as well as the patterns of up-titration following initiation of therapy in people with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This was a retrospective cohort study of adults with T2DM in the United Kingdom (UK). Metformin dose distribution was assessed at 0, 6 and 12 months in people initiating metformin monotherapy (new users) and cross-sectionally in people with ongoing metformin monotherapy (prevalent users). Patterns and predictors of up-titration were also analysed in new users. Dose distributions and treatment patterns were assessed descriptively; predictors of up-titration were determined using multivariable logistic regressions. RESULTS: Totals of 6174 new users and 8733 prevalent users were included. New users initiated metformin at >0 mg to ≤500 mg (25%), >500 mg to ≤1000 mg (47%), >1000 mg to ≤1500 mg (17%) or >1500 mg to ≤2000 mg (12%) daily. This distribution did not vary over time. Prevalent users of metformin received doses of >0 mg to ≤500 mg (14%), >500 mg to ≤1000 mg (40%), >1000 mg to ≤1500 mg (15%), >1500 mg to ≤2000 mg (29%) or >2000 mg (1%) daily. Among new users of metformin, 6.7% and 10.8% had been up-titrated at 6 and 12 months, respectively, despite the majority having glycated haemoglobin >53 mmol/mol. Predictors of up-titration included younger age and higher HbA1c. CONCLUSIONS: A majority of T2DM patients taking metformin received a dose ≤1000 mg/day. Up-titration of metformin is infrequent in the first year postinitiation.

Psychosocial mechanisms of a behavioral treatment for urinary incontinence of prostate cancer survivors.

Purpose: We examined underlying psychosocial processes of a behavioral treatment for urinary incontinence (UI) of prostate cancer survivors.Design: Secondary analysis of data collected from a clinical trial.Sample: Two hundred forty-four prostate cancer survivors who participated in a clinical trial of behavioral intervention to UI as intervention or control subjects.Methods: The participants had a 3-month behavioral intervention or usual care and were followed up for an additional 3 months. They were assessed at baseline, 3, and 6 months. Latent growth curve models were performed to examine trajectories of each study variable and relationships among the variables.Findings: Increasing self-efficacy and social support were significantly and independently associated with more reduction of urinary leakage frequency over time.Implications for psychosocial oncology: Providing problem-solving skills and social support, including peer support, are essential for empowering patients to reduce UI.