Healthcare resource utilization and cost among individuals with late-onset versus adult-onset Huntington's disease: a claims­based retrospective cohort study.

AIMS: Quantify healthcare resource utilization (HRU) and costs for individuals with late-onset Huntington's disease (LoHD) and compare these with adult-onset HD (AoHD) and non-HD controls. METHODS: This retrospective cohort study used US healthcare claims data from the IBM MarketScan Commercial and Medicare Supplemental Databases. Individuals newly diagnosed with HD between 1/1/2009 and 12/31/2017 were selected (index date was first HD claim). Individuals ≥60 years of age at the index date were categorized as having LoHD while individuals 21-59 years of age were categorized as having AoHD. Non­HD controls were exact matched 2:1 to LoHD and AoHD cohorts. Individuals were required to have continuous enrollment for ≥12 months pre- and post-index. Twelve-month all-cause HRU and healthcare costs were assessed for each cohort. RESULTS: In total, 763 individuals with LoHD and 1,073 individuals with AoHD were matched with 3,762 non-HD controls. Unadjusted all-cause HRU in the 12 months post-index was higher for individuals with LoHD and AoHD compared with non-HD controls across most service categories. Adjusted all-cause HRU for the LoHD cohort was significantly higher compared with non-HD controls across all service categories. In the 12 months post-index, mean total costs for the LoHD cohort ($29,055) were significantly higher than for non-HD controls (≥60 years old: $17,286; 21-59 years old: $12,688; p <.001) and similar to total costs in the AoHD cohort ($31,701; p =.47). LIMITATIONS: It was not possible to control for differences in HD stage but regression models were adjusted for baseline HRU. Evaluations of costs did not include indirect costs, which are known to be significant components of the wider HD burden. CONCLUSIONS: This study provides the first analysis of HRU and costs in LoHD, demonstrating that individuals with LoHD experience a significantly higher healthcare burden compared with non-HD controls and a similarly high burden compared with individuals with AoHD.

Huntington's disease (HD) usually develops between the ages of 30­50 but can develop earlier/later. This study looked at healthcare use in people who developed HD at age 60 or later in the United States. Researchers found that people who develop HD at age 60 or later have similar health needs to people with adult-onset HD. Furthermore, they have much greater health needs than people of a similar age who do not have HD.

Burden of influenza in patients with cardiovascular disease who receive antiviral treatment for influenza.

AIMS: Cardiovascular disease (CVD) increases the risk of complications from respiratory viruses, including influenza. Moreover, respiratory viruses may increase the risk of CV events. Antiviral medication may reduce healthcare resource utilization (HRU), but more data is needed in CVD populations to explore relationships between influenza antiviral treatment, CVD-related complications, HRU, and costs. MATERIALS AND METHODS: This retrospective claims analysis examined data extracted from IBM MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases during three influenza seasons: 2016-2017, 2017-2018, or 2018-2019. Propensity score matching was used to compare HRU outcomes and costs among CVD patients treated with influenza antivirals and untreated patients. RESULTS: Across all influenza seasons, patients with CVD and influenza who received antiviral treatment had fewer all-cause emergency department (ED) visits (p < .01), respiratory-related HRU (p < .01), respiratory-related outpatient and ED visits (both p < .01), CVD-related HRU (p < .01), heart failure-related HRU visits (p < .01), and kidney failure-related HRU (p < .01) 180 days post-treatment fill date than CVD patients untreated for influenza. CVD patients treated with antivirals also had a lower mean number of all-cause inpatient, outpatient, and ED visits and days of stay (all p < .01) and fewer mean respiratory-related outpatient and ED visits (both p < .01). HRU patterns were generally consistent over time and across individual influenza seasons. Finally, treated CVD patients incurred lower all-cause outpatient costs 180 days post-treatment fill date (p < .05) than CVD patients untreated for influenza. CONCLUSION: CVD patients who contract influenza and take antiviral medication have fewer short- and long-term influenza-related complications and less overall HRU compared with CVD patients who were not prescribed antiviral treatments. Antiviral treatment may be an important tool in reducing complications in CVD patients with influenza.

People with heart disease are more likely to have complications from respiratory viruses, including influenza (flu). Moreover, respiratory viruses may increase the risk of damage to the heart muscle. We examined whether patients with heart disease who get the flu and take prescription medications called antiviral drugs have fewer short- and long-term flu-related complications and use fewer healthcare services than patients with heart disease who do not take antiviral drugs.We examined commercial and Medicare databases during three influenza seasons (2016­2017, 2017­2018, and 2018­2019), and we compared outcomes and costs among heart disease patients who were treated or not treated with antiviral drugs. Patients with heart disease and the flu who received antiviral drugs had fewer visits to the emergency room, used fewer healthcare services for respiratory-related problems, used fewer heart disease-related healthcare services, and had fewer heart failure-related or kidney failure-related healthcare visits than heart disease patients who were not treated for the flu. Finally, patients with heart disease who were treated with antiviral drugs spent less money on outpatient services than patients with heart disease who were not treated with antiviral drugs.We determined that patients who get the flu and take antiviral drugs have fewer short- and long-term flu-related complications and use fewer healthcare services than heart disease patients who do not receive antiviral drugs. Therefore, it may be important to treat heart disease patients with antiviral drugs in order to reduce the number of flu-related complications in these patients.

Antiviral Use and Health Care Use Among US Patients With Rheumatoid Arthritis and Influenza in Three Influenza Seasons, 2016-2019.

OBJECTIVE: Patients with rheumatoid arthritis (RA) are vulnerable to severe complications of influenza. We assessed whether health care resource use (HRU) and costs differed between patients with RA and influenza who received antiviral medication compared with matched patients with RA and influenza not receiving antiviral therapy. METHODS: This was a retrospective US health insurance claims analysis over three influenza seasons (each October to April) in 2016-2019. Adults with RA and a subsequent diagnosis of influenza were included. Treated patients (receiving antiviral influenza treatment within 2 days of diagnosis) and untreated patients were propensity score matched using baseline covariates. HRU and costs were assessed for inpatient, emergency department (ED), and outpatient visits and compared between cohorts using χ2 tests and t tests. RESULTS: After matching, 2638 treated and 1319 untreated patients were included. For treated versus untreated patients, the mean number of all-cause outpatient visits was 0.96 versus 1.21 during 14 days of follow-up (P < 0.001) and 1.94 versus 2.24 over 28 days (P = 0.001), respectively. Over 28 days, the mean number of all-cause ED visits was lower among treated (0.23) than untreated (0.30) patients (P = 0.042). The mean number of respiratory-related outpatient visits was significantly lower for treated versus untreated patients, and mean costs for these visits were $17.89 versus $35.27 over 14 days (P < 0.001) and $28.92 versus $48.77 over 28 days (P < 0.001) for treated versus untreated patients, respectively. CONCLUSION: Our findings demonstrate that prompt antiviral treatment after influenza diagnosis may reduce HRU and costs in patients with RA.

Front-line treatment patterns in multiple myeloma: An analysis of U.S.-based electronic health records from 2011 to 2019.

Multiple myeloma (MM) treatment options have evolved rapidly, but how new agents are incorporated into treatment decisions in current practice is not well understood. This study examined prescribing trends of physicians treating newly diagnosed MM and treatment outcomes in the United States. Electronic health record data from 6271 adult patients diagnosed with MM and receiving initial treatment between 1 January 2011 and 31 January 2020 were derived from the Flatiron Health electronic-health record de-identified database. The number/types of agents included in therapy regimens, time to next treatment (TTNT), and overall survival (OS) were assessed. Subgroups were analyzed by the International Staging System (ISS) disease stage at diagnosis, stem cell transplant eligibility and timing, and practice type. Exploratory prognostic models evaluated the association between baseline covariates and time-to-event outcomes. The proportion of patients receiving triplet therapies increased from 2011 (36%) to 2019 (72%) as those receiving initial monotherapy or doublet therapy decreased. Overall, the most prevalent triplet regimen consisted of an immunomodulatory drug (IMiD), a proteasome inhibitor, and a steroid. From 2017 to 2019, median TTNT from front-line to second-line was longer in patients with ISS stage I versus stages II/III, and in those receiving IMiD-containing doublet or triplet therapies versus other combinations. Overall median OS was 56 months and increased from 2011 to 2014, after which median OS was not yet reached. Age, ISS stage, and high-risk status were prognostic for both OS and TTNT, while sex, practice type, and ECOG status were prognostic for OS only.

Matching-adjusted indirect treatment comparison of ozanimod versus teriflunomide for relapsing multiple sclerosis.

BACKGROUND: A growing number of immunomodulating disease-modifying therapies are available for treatment of relapsing multiple sclerosis (RMS). In the absence of randomized head-to-head trials, matching-adjusted indirect comparisons (MAICs) can be used to adjust for cross-trial differences and evaluate the comparative efficacy and safety of these agents. We used MAIC methodology to indirectly compare key outcomes with ozanimod (OZM) and teriflunomide (TERI) in the treatment of RMS. METHODS: A systematic literature review was conducted to identify clinical trials evaluating the efficacy and safety of OZM vs TERI. Given the absence of head-to-head trials of OZM vs TERI, we used a matching-adjusted indirect comparison to adjust for potential treatment effect modifiers and prognostic factors while assessing confirmed disability progression (CDP), relapse, and safety outcomes. Individual patient data for OZM (SUNBEAM and RADIANCE Part B trials) and aggregate level data for TERI (ASCLEPIOS I/II, TOWER, OPTIMUM, and TEMSO trials) were used to evaluate the following outcomes: annualized relapse rate (ARR), proportion of patients relapsed, CDP at 3 and 6 months, overall adverse events (AEs), serious AEs (SAEs), and discontinuations due to AEs. RESULTS: After matching, baseline patient characteristics were balanced between OZM and TERI. Compared with TERI, OZM demonstrated significant improvements in ARR (rate ratio: 0.73; 95% CI: 0.62-0.84), proportion of patients relapsed (odds ratio [OR]: 0.56; 95% CI: 0.44-0.70), overall AEs (OR: 0.35; 95% CI: 0.29-0.43), SAEs (OR: 0.53; 95% CI: 0.37-0.77), and discontinuations due to AEs (OR: 0.14; 95% CI: 0.09-0.21). OZM demonstrated statistically significant improvements in CDP at 3 months (hazard ratio [HR]: 0.78; 95% CI: 0.66-0.92) but nonsignificant differences at 6 months (HR: 0.78; 95% CI: 0.60-1.01) compared with TERI. CONCLUSION: In this indirect treatment comparison of patients with RMS, OZM appeared to have an improved benefit-risk profile over TERI.

Comparative Efficacy and Safety of Ozanimod and Dimethyl Fumarate for Relapsing-Remitting Multiple Sclerosis Using Matching-Adjusted Indirect Comparison.

BACKGROUND: Patients with multiple sclerosis (MS) experience relapses and sustained disability progression. Since 2004, the number of disease-modifying therapies (DMTs) for MS has grown substantially. As a result, patients, healthcare providers, and insurers are increasingly interested in comparative efficacy and safety evaluations to distinguish between treatment options, but head-to-head studies between DMTs are limited. OBJECTIVE: The aim of the current study was to compare efficacy and safety outcomes with the DMTs ozanimod and dimethyl fumarate (DMF) using a matching-adjusted indirect comparison (MAIC) to adjust for cross-trial differences in study design and population. METHODS: A systematic literature review was performed to identify clinical studies evaluating the efficacy and safety of ozanimod compared with DMF. Individual patient-level data (IPD) for ozanimod were obtained from the SUNBEAM and RADIANCE Part B trials, and aggregate-level patient data (APD) for DMF were obtained from CONFIRM and DEFINE. A MAIC is used to weight IPD to APD based on important baseline patient characteristics considered to be effect modifiers or prognostic factors in order to balance the covariate distribution to establish more homogenous trial populations. Once trial populations are determined to be sufficiently homogenous, outcomes of interest are estimated and used to generate treatment effects between the weighted IPD and APD. We used MAIC methodology to compare efficacy and safety outcomes of interest between ozanimod 1.0 mg once daily (OD) and DMF 240 mg twice daily (BID), including confirmed disability progression (CDP) at 3 and 6 months, annualized relapse rate (ARR), proportion of patients relapsed, overall adverse events (AEs), serious AEs (SAEs), and discontinuations due to AEs. RESULTS: After matching patient data, baseline patient characteristics were balanced between patients receiving ozanimod and those receiving DMF. Compared with DMF, ozanimod demonstrated significantly improved CDP at 3 months (hazard ratio 0.67; 95% confidence interval [CI] 0.53-0.86), ARR (rate ratio [RR] 0.80; 95% CI 0.67-0.97), proportion of patients relapsed (odds ratio [OR] 0.66; 95% CI 0.52-0.83), overall AEs (OR 0.11; 95% CI 0.08-0.16), SAEs (OR 0.27; 95% CI 0.19-0.39), and discontinuations (OR 0.11; 95% CI 0.07-0.17). CDP at 6 months did not differ significantly between the two agents (RR 0.89; 95% CI 0.62-1.26). CONCLUSIONS: After adjustment of baseline patient characteristics, the MAIC demonstrated that the efficacy and safety of ozanimod 1.0 mg OD was superior to that of DMF 240 mg BID. Although a MAIC is less likely to produce biased estimates than a naïve or a standard indirect treatment comparison via a common comparator, limitations include potential confounding due to unobserved and thus unaccounted for baseline differences.

Ozanimod and dimethyl fumarate (DMF) are disease-modifying therapies used to treat relapsing-remitting multiple sclerosis (MS). Comparative efficacy and safety evaluation is important to key patients, healthcare providers, and health insurers; however, head-to-head studies between MS therapies are limited. In this analysis, we used an indirect treatment comparison method, specifically a matching-adjusted indirect comparison (MAIC), to compare results of clinical trials of ozanimod and DMF. In this MAIC, findings suggested that ozanimod was associated with greater reductions of relapses, a lowered risk of disability progression at 3 months, and improved safety outcomes compared with DMF. Although MAICs were conducted while adjusting for important treatment-effect modifiers and/or prognostic factors, the possibility of confounding as a result of unobserved baseline differences remains. Such an issue can be resolved only by conducting a head-to-head treatment comparison in a randomized clinical trial.

An indirect treatment comparison of the efficacy of pembrolizumab versus competing regimens for the adjuvant treatment of stage III melanoma.

Objective: To determine the efficacy of pembrolizumab relative to other treatments used in stage III melanoma by conducting a systematic literature review (SLR) and network meta-analysis (NMA). Methods: A SLR was conducted to identify randomized clinical trials (RCTs) evaluating approved adjuvant treatments including interferon-containing regimens, BRAF-inhibitors, and PD-L1 inhibitors in stage III melanoma patients. Relative treatment effects for recurrence-free survival (RFS) were synthesized with Bayesian NMA models that allowed for hazard ratios (HRs) to vary over time. Results: Included studies formed a connected network of evidence composed of eight trials. In high-risk stage III patients, the HR for pembrolizumab vs observation decreased significantly over time with the superiority of pembrolizumab over observation becoming statistically meaningful before 3 months. By 9 months, the HR for pembrolizumab vs observation was statistically significantly lower than the HR for most other treatments vs observation, with the exception of ipilimumab and biochemotherapy due to overlapping 95% credible intervals. In BRAF + patients, pembrolizumab was statistically significantly better than observation after 3 months. The HR for both BRAF-inhibitors vs observation increased significantly over time and pembrolizumab was statistically superior to both BRAF-inhibitors after 15 months. Conclusions: Pembrolizumab results in statistically significantly improved RFS compared to all competing regimens after 9 months, except ipilimumab and biochemotherapy, for the adjuvant treatment of stage III melanoma. However, point estimate HRs vs observation for pembrolizumab are much lower than those for ipilimumab. In BRAF + patients, the advantage of pembrolizumab versus competing interventions increases over time with respect to RFS.

Pembrolizumab plus chemotherapy for first-line treatment of metastatic nonsquamous non-small-cell lung cancer: a network meta-analysis.

AIM: A systematic review and network meta-analysis were conducted to evaluate the efficacy of pembrolizumab + pemetrexed + platinum relative to other regimens in metastatic nonsquamous non-small-cell lung cancer (NSq-NSCLC). PATIENTS & METHODS: Eligible studies evaluated first-line regimens in NSq-NSCLC patients without known targetable mutations. Relative treatment effects were synthesized with random effects proportional hazards Bayesian network meta-analyses. RESULTS: The hazard ratio (HR) for overall survival (OS) for pembrolizumab + pemetrexed + platinum was statistically significant over all platinum-doublet (HR range: 0.42-0.61), platinum-doublet + bevacizumab (HR range: 0.44-0.53) and platinum-doublet + atezolizumab regimens (HR range: 0.56-0.62). Additionally, pembrolizumab + pemetrexed + platinum numerically improved OS over atezolizumab + paclitaxel + carboplatin + bevacizumab (HR: 0.65; 95% credible interval: 0.43, 1.01). Pembrolizumab + pemetrexed + platinum had 95.6% probability of being the best treatment regimen for OS. CONCLUSION: Pembrolizumab + pemetrexed + platinum is likely the most efficacious first-line regimen for metastatic NSq-NSCLC.