Evaluating the real-world effectiveness of belimumab in patients with SLE using SLE-related laboratory values and rheumatoid arthritis-derived disease activity measures: RAPID3, swollen joint count and tender joint count.

OBJECTIVE: To investigate the real-world impact of intravenous belimumab treatment among patients with SLE using rheumatoid arthritis-derived disease activity measures and SLE-related laboratory values. METHODS: This retrospective cohort study used US electronic medical record data from the United Rheumatology Normalised Integrated Community Evidence (UR-NICE) database. Adult patients with SLE who initiated intravenous belimumab between 1 January 2012 and 3 December 2019 (index), had 12 months of pre-index and 24 months of post-index clinical activity, and had ≥6 infusions of belimumab during the 24 months post-index were included. The primary outcome measure was time to first improvement of minimally important difference (MID) for Routine Assessment of Patient Index Data 3 (RAPID3), Patient Pain Index (PPI), swollen joint count, tender joint count (TJC), complement C3 and C4 and anti-double-stranded DNA antibodies during the on-treatment follow-up period of up to 24 months. The secondary outcome measure evaluated the trajectories of these outcome measures for up to 24 months of belimumab treatment. RESULTS: Of 495 patients included, between 21.0% and 52.1% had ≥1 record for each of the disease activity measures or laboratory values in the pre-index and post-index periods and were included in analyses for that measure. The proportion of patients achieving MID for each measure increased rapidly within 3 months, with continued gradual improvement throughout the remaining on-treatment period, up to 24 months. After 6 months, 52.3% and 55.3% of patients had achieved MID in RAPID3 and PPI, respectively. Outcome measure trajectories indicated improved disease activity with belimumab treatment, particularly in RAPID3, TJC and laboratory values. CONCLUSIONS: In this real-world effectiveness study, belimumab therapy for SLE resulted in clinically meaningful improvements in rheumatoid arthritis-derived disease activity measures within 3 months of treatment, with patients who remained on belimumab therapy experiencing improvement even up to 24 months of observation.

Real-world association between systemic corticosteroid exposure and complications in US patients with severe asthma.

BACKGROUND: Systemic corticosteroid (SCS) use remains widespread among patients with severe asthma, despite associated complications. OBJECTIVE: Evaluate the association between cumulative SCS exposure and SCS-related complications in severe asthma. METHODS: This retrospective, longitudinal study used claims data from the Optum Clinformatics Data Mart database (GSK ID: 214469). Eligible patients (≥ 12 years old) had an asthma diagnosis and were divided into two cohorts: SCS use and non/burst-SCS use. Patients in the SCS use cohort had a claim for a daily prednisone-equivalent dose ≥ 5 mg SCS following ≥ 6 months of continuous SCS use; those in the non/burst-SCS cohort had no evidence of continuous SCS use and had a non-SCS controller/rescue medication initiation claim. For each cohort, the date of the qualifying claim was the index date. SCS users were further stratified by SCS use during each quarter of follow-up: low (≤ 6 mg/day), medium (> 6-12 mg/day), high (> 12 mg/day), and continuous high (≥ 20 mg/day for 90 days). SCS-related complications were evaluated in the quarter following SCS exposure. The adjusted odds ratios (OR) of experiencing SCS-related complications during follow-up in each of the SCS use groups versus the non/burst SCS cohort were calculated using generalized estimating equations models. RESULTS: SCS and non/burst-SCS use cohorts included 7473 and 89,281 patients (mean follow-up: 24.6 and 24.2 months), respectively. Compared with the non/burst-SCS use cohort, medium, high, and continuous high SCS use was associated with greater odds of any SCS-related complication (adjusted OR [95% confidence interval]: 1.30 [1.21, 1.39], 1.49 [1.35, 1.64] and 1.63 [1.40, 1.89], respectively) including increased acute gastrointestinal, cardiovascular, and immune system-related complications, and chronic cardiovascular, metabolic/endocrine, central nervous system, bone-/muscle-related, ophthalmologic, and hematologic/oncologic complications. Low-dose SCS use was also associated with significantly increased odds of acute gastrointestinal and immune system-related complications, and chronic bone-/muscle-related and hematologic/oncologic complications versus the non/burst-SCS use cohort. CONCLUSION: SCS use, even at low doses, is associated with increased risk of SCS-related complications among patients with severe asthma.

Impact of formulary-related pharmacy claim rejections of cariprazine on health care utilization and treatment patterns among patients with bipolar I disorder.

BACKGROUND: Formulary restrictions, intended to limit inappropriate medication use and decrease pharmacy costs, may prevent or delay patients with bipolar I disorder from initiating cariprazine, a dopamine D3-preferring D3/D2 and serotonin 5HT1A receptor partial agonist that is approved to treat manic/mixed or depressive episodes associated with bipolar I disorder. Little is known about the downstream consequences of formulary-related cariprazine prescription rejections. OBJECTIVE: To evaluate the impact of formulary-related cariprazine claim rejections on health care resource utilization (HCRU) and treatment patterns among patients newly prescribed cariprazine for bipolar I disorder. METHODS: Symphony Health Integrated Dataverse was used to identify commercially insured adults (aged ≥18 years) with bipolar I disorder and at least 1 pharmacy claim for cariprazine (rejected because of formulary restrictions or approved; date of the first claim is the index date) from March 2015 through October 2020. Formulary-related rejection reasons included noncoverage, prior authorization requirement, and step therapy requirement. Baseline characteristics were evaluated during the 12 months pre-index and balanced between rejected and approved cohorts using 1:2 propensity score matching. HCRU outcomes included all-cause and mental health (MH)-related hospitalizations, emergency department (ED) visits, and outpatient visits. Treatment patterns were analyzed descriptively and included treatment delay and atypical antipsychotic use. HCRU was reported per patient-year and compared between cohorts using rate ratios; 95% CIs and P values were calculated using nonparametric bootstrap procedures. RESULTS: The matched rejected and approved cohorts comprised 1,554 and 3,108 patients, respectively. The rejected cohort had 22% more all-cause and 24% more MH-related hospitalizations per patient-year vs the approved cohort (rate ratio [95% CI], all-cause: 1.22 [1.01-1.48], P = 0.024; MH-related: 1.24 [1.01-1.55], P = 0.044). ED and outpatient visits were numerically, but not significantly, greater in the rejected cohort. Of patients in the rejected cohort, 34.7% never received an atypical antipsychotic and 76.8% never received cariprazine. For those who later received cariprazine or another atypical antipsychotic, the average treatment delay was approximately 6 months (188 days) and approximately 4 months (123 days) after the initial rejection, respectively. CONCLUSIONS: Patients with bipolar I disorder and formulary-related cariprazine claim rejections experienced significantly more hospitalizations than patients whose initial claim was approved; ED and outpatient visits were similar between cohorts. Less than a quarter of patients whose initial claim was rejected later received cariprazine, and more than one-third never received any atypical antipsychotic. To our knowledge, this is the first study to evaluate the impact of formulary-related rejections of cariprazine on HCRU and treatment patterns in patients with bipolar I disorder.

The real-world health resource use and costs of misdiagnosing bipolar I disorder.

BACKGROUND: Misdiagnosis of bipolar I disorder (BP-I) as major depressive disorder (MDD) is common. This study evaluated healthcare resource utilization (HRU) and costs among BP-I patients who were initially misdiagnosed with MDD (misdiagnosed BP-I cohort) versus patients diagnosed with BP-I without a known prior MDD diagnosis (BP-I only cohort). METHODS: Data from IBM® MarketScan® Research Databases were used. The index date was the first MDD diagnosis for misdiagnosed patients or first BP-I diagnosis for BP-I only patients. Inverse probability of treatment weighting was used to balance baseline characteristics between cohorts. All-cause and mental health (MH)-related HRU and costs were compared between weighted cohorts using rate ratios (RRs) and mean cost differences, respectively. Outcomes were reported per patient-year (PPY). Confidence intervals and P-values were calculated using non-parametric bootstrap procedures. RESULTS: Overall, 14,729 misdiagnosed BP-I and 16,072 BP-I only patients met criteria. Baseline characteristics were balanced across weighted cohorts. Misdiagnosed BP-I patients had significantly higher rates of hospitalizations, emergency room visits, and outpatient visits than BP-I only patients during follow-up (all-cause RRs: 1.94, 1.33, and 1.38, respectively, all P < .001; MH-related RRs: 2.19, 1.77, and 1.77, respectively, all P < .001). Similarly, misdiagnosed BP-I patients incurred significantly higher total healthcare costs PPY over follow-up (all-cause: $21,202 vs $14,661, cost difference = $6541; MH-related: $12,901 vs $6749, cost difference = $6152; both P < .001). Cost differences were even higher during the first year (all-cause = $7146; MH-related = $6619; both P < .001). LIMITATIONS: Claims database (e.g., coding inaccuracies); generalizability to uninsured patients. CONCLUSIONS: The prompt and correct diagnosis of BP-I may significantly reduce HRU and costs.

Impact of adherence to treatment with inhaled corticosteroids/long-acting ß-agonists on asthma outcomes in the United States.

BACKGROUND: Suboptimal adherence to maintenance medication has been associated with poor outcomes in asthma. This study examined single-inhaler inhaled corticosteroid (ICS)/long-acting ß2 agonist (LABA) adherence and asthma-related outcomes. METHODS: This retrospective observational study of patients with asthma initiating ICS/LABA used data from IQVIA PharMetrics Plus (1 January 2014-31 March 2019). Patients included were ⩾18 years old and had ⩾12 months continuous eligibility before, and ⩾180 days follow-up after, the index date. Adherence was measured as proportion of days covered ([PDC] adherent ⩾ 0.8; non-adherent <0.8) each quarter, with outcomes measured each subsequent quarter. Endpoints were asthma-related overall and severe (inpatient/emergency department [ED] visit) exacerbations, rescue medication use, and asthma-related healthcare resource utilization and costs. Regression models evaluated associations between adherence and outcomes, controlling for repeated measures and differences in baseline characteristics. RESULTS: Overall, 50,037 patients were included (mean age 45.3 years; mean follow-up 23.3 months). Adherent patients were less likely to experience asthma-related overall (adjusted odds ratio [aOR] 95% confidence interval [CI]: 0.942 [0.890, 0.998]; p = 0.041), or severe exacerbations (aOR [95% CI]: 0.778 [0.691, 0.877]; p < 0.001) per quarter versus non-adherent patients. Adherent patients had lower severe exacerbation rates (adjusted rate ratio [aRR] [95% CI]: 0.792 [0.702, 0.893]; p < 0.001) but similar overall exacerbation rates (aRR [95% CI]: 0.993 [0.945, 1.044]; p = 0.783) versus non-adherent patients. The odds of rescue medication use were lower per 20% PDC increase (aOR [95% CI] short-acting ß2 agonist: 0.991 [0.985, 0.996]; p = 0.001; oral corticosteroid: 0.988 [0.982, 0.995]; p < 0.001). Adherent patients were less likely to visit EDs per quarter (aOR [95% CI]: 0.775 [0.680, 0.883]; p < 0.001) and odds of hospitalization were lower per 20% PDC increase (aOR [95% CI]: 0.930 [0.881, 0.982]; p = 0.009). Across most measures, adherent patients incurred lower costs. CONCLUSION: This real-world study highlights the short-term clinical and economic benefits of ICS/LABA adherence in asthma, particularly in reducing severe exacerbations.

Adherence and Persistence to Single-Inhaler Versus Multiple-Inhaler Triple Therapy for Asthma Management.

BACKGROUND: Treatment guidelines recommend triple therapy for patients with asthma who remain uncontrolled on inhaled corticosteroid/long-acting ß2-agonist therapy. Previously, triple therapy was only available via multiple inhalers. Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) is approved as maintenance treatment for asthma; however, real-world information on adherence and persistence is limited. OBJECTIVE: To compare adherence and persistence among adult patients with asthma receiving single-inhaler FF/UMEC/VI versus multiple-inhaler triple therapy (MITT) in the United States. METHODS: This retrospective cohort study used IQVIA PharMetrics Plus data to evaluate patients with asthma who initiated once-daily FF/UMEC/VI 100/62.5/25 mcg or MITT between September 18, 2017, and September 30, 2019. Inverse probability weighting and multivariable regression adjusted for differences in characteristics between the FF/UMEC/VI and MITT cohorts. Adherence was assessed using proportion of days covered (PDC) and proportion of patients achieving PDC ≥0.8 and PDC ≥0.5. Non-persistence was identified as a >45-day gap between fills. RESULTS: The study included 1396 FF/UMEC/VI and 5115 MITT initiators. Three months after initiation, FF/UMEC/VI users had significantly higher mean PDC versus MITT users (0.68 vs 0.59; P < .001) and 31% more likely to be adherent (PDC ≥0.8; 40.6% vs 31.3%; adjusted risk ratio [95% confidence interval (CI)]: 1.31 [1.13-1.54]; P < .001). Similar patterns were observed at 6 and 12 months post initiation. In addition, FF/UMEC/VI users were 49% more likely to persist at 12 months than MITT users (25.9% vs 15.1%, adjusted hazard ratio [95% CI]: 1.49 [1.39-1.60]; P < .001). CONCLUSIONS: Patients with asthma initiating triple therapy with FF/UMEC/VI had significantly better adherence and persistence compared with MITT initiators.

Adherence and persistence to once-daily single-inhaler versus multiple-inhaler triple therapy among patients with chronic obstructive pulmonary disease in the USA: A real-world study.

BACKGROUND: Triple therapy comprising an inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting ß2 agonist (ICS/LAMA/LABA) is recommended for chronic obstructive pulmonary disease (COPD) patients at risk of exacerbation. Multiple-inhaler triple therapy (MITT) is associated with poor adherence and persistence; however, these outcomes have not been evaluated for single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI). METHODS: This retrospective analysis of the IQVIA PharMetrics Plus claims database identified patients with COPD initiating triple therapy between 18 September 2017 and 30 June 2019. The first date of single-inhaler FF/UMEC/VI dispensing, or first day of overlapping ICS, LAMA, and LABA medications for MITT users, defined the index date. Patients were ≥40 years, had ≥12 months of continuous insurance coverage pre-index (baseline) and ≥6 months' coverage post-index; those with MITT during baseline were excluded. Inverse probability weighting was used to balance baseline characteristics. Adherence was assessed using proportion of days covered (PDC) and was evaluated using linear and log-binomial models. Persistence (non-persistence identified as >30-day gap between fills) was evaluated using Cox models. RESULTS: 9942 patients (FF/UMEC/VI: 2782; MITT: 7160) were included. Adherence was significantly higher for FF/UMEC/VI versus MITT users (mean PDC, 0.66 vs. 0.48; p < 0.001), and FF/UMEC/VI users were twice as likely to be adherent (PDC ≥0.8) than MITT users (46.5% vs. 22.3%; risk ratio [95% CI]: 2.08 [1.85-2.30]; p < 0.001). After 12 months, significantly more FF/UMEC/VI users persisted on therapy than MITT users (35.7% vs. 13.9%; hazard ratio [95% CI]: 1.91 [1.81-2.01]; p < 0.001). CONCLUSIONS: COPD patients initiating single-inhaler FF/UMEC/VI had significantly improved adherence and persistence compared with MITT.

Benefit of Prompt versus Delayed Use of Single-Inhaler Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) Following a COPD Exacerbation.

Purpose: Triple therapy (TT; inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting ß2-agonist) is recommended for patients with chronic obstructive pulmonary disease (COPD) at risk of exacerbation, although the optimum timing of TT initiation remains unclear. This study evaluated the impact of prompt versus delayed initiation of single-inhaler TT (fluticasone furoate, umeclidinium, and vilanterol [FF/UMEC/VI]) following a COPD exacerbation. Patients and Methods: This retrospective cohort study used data from the IQVIA PharMetrics® Plus database. Patients initiating FF/UMEC/VI following a COPD exacerbation between September 18, 2017 and September 30, 2019 (exacerbation = index date) were categorized as prompt (within 30 days of index) or delayed (31-180 days after index) FF/UMEC/VI initiators. Patients were aged ≥40 years at index, had ≥12 months' continuous health insurance coverage before index (baseline), and ≥6 months' coverage after index (follow-up). Patients with a COPD exacerbation or claim for FF/UMEC/VI during baseline were excluded. Inverse probability weighting was used to adjust for differences in baseline characteristics between cohorts. Exacerbations (overall, moderate, and severe), healthcare costs, and readmissions were evaluated during follow-up. Results: A total of 1904 patients (prompt: 529; delayed: 1375) were included. After weighting, baseline characteristics were well balanced between cohorts. Patients in the prompt cohort had significantly lower rates per person-year (PPY) of overall (0.98 vs 1.23; rate ratio [RR] [95% CI] = 0.79 [0.65-0.94], p = 0.004), moderate (0.86 vs 1.03; RR [95% CI] = 0.84 [0.69-0.99], p = 0.038), and severe (0.11 vs 0.20; RR [95% CI] = 0.57 [0.37-0.79], p = 0.002) exacerbations, compared with delayed initiators. Mean all-cause and COPD-related healthcare costs were significantly lower among prompt initiators (all-cause: $26,107 vs $32,400 PPY, p = 0.014; COPD-related: $12,694 vs $17,640 PPY, p = 0.002). Conclusion: Prompt initiation of FF/UMEC/VI following a moderate or severe COPD exacerbation was associated with significant reductions in exacerbations and healthcare costs relative to delayed initiation.

Healthcare costs of patients with cancer stratified by Khorana score risk levels.

AIMS: Patients with cancer are at high risk of venous thromboembolism (VTE), which entails a high economic burden. The risk of cancer-associated VTE can be assessed using the Khorana score (KS), a validated VTE risk prediction algorithm. This study compared healthcare costs associated with different KS in a population of patients newly diagnosed with cancer. METHODS: The Optum Clinformatics DataMart database (01/01/2012-09/30/2017) was used to select adult patients with ≥1 hospitalization or ≥2 outpatient claims with a cancer diagnosis (index date) initiated on systemic therapy or radiation therapy. Patients were classified in mutually exclusive cohorts based on KS (i.e. KS = 0, 1, 2 or ≥3). The observation period spanned from index to the earliest among the end of data availability, death, end of insurance coverage, or 12 months. RESULTS: In total 6,194 patients (KS = 0: 2,488; KS = 1: 2,125; KS = 2: 1,074; KS ≥ 3: 507) were included. On average, patients were aged 68 years, 48-52% were female, and the Quan-Charlson comorbidity index ranged between 1.1 and 1.4. Over the observation period, all-cause total healthcare costs per patient per month (PPPM) were $8,826 (KS = 0), $11,598 (KS = 1), $14,028 (KS = 2), and $16,211 (KS ≥ 3). Using the KS = 0 cohort as a reference, adjusted PPPM costs were $2,506, $4,775, and $6,452 higher in the KS = 1, KS = 2, and KS ≥ 3 cohorts, respectively. Hospitalization and outpatient costs were the main drivers of these differences. Similar results were found for VTE-related costs, which represented 4-11% of the total all-cause cost difference between KS cohorts. LIMITATIONS: Residual confounders; results may not be generalized to patients with other insurance plans or those who received treatments other than systemic therapy or radiation therapy. CONCLUSIONS: This real-world analysis found that cancer patients at higher risk of VTE (based on KS) incurred significantly greater all-cause and VTE-related healthcare costs compared with cancer patients at lower risk of VTE.

Hospital Admission and Readmission Among US Patients Receiving Umeclidinium/Vilanterol or Tiotropium as Initial Maintenance Therapy for Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Patients hospitalized for chronic obstructive pulmonary disease (COPD) exacerbations are at risk of further readmissions, increased treatment costs, and excess mortality. This study evaluated inpatient admissions and readmissions in patients receiving initial maintenance therapy with umeclidinium/vilanterol (UMEC/VI) versus tiotropium (TIO). METHODS: This retrospective, matched cohort study identified patients with COPD who initiated maintenance therapy with UMEC/VI or TIO from Optum's de-identified Clinformatics Data Mart database between January 1, 2013, and December 31, 2018 (index date defined as earliest dispensing). Eligibility criteria included: ≥ 1 medical claim for COPD pre-index or on the index date; ≥ 12 months of continuous eligibility pre-index; age ≥ 40 years at index; no pre- or post-index asthma diagnosis; and no pre-index claims for medications containing inhaled corticosteroids, long-acting ß2-agonists, or long-acting muscarinic antagonists. Outcomes included time to first on-treatment COPD-related inpatient admission, rate of on-treatment COPD-related admissions, and rate of all-cause and COPD-related readmissions within 30 and 90 days. Propensity score matching was used to adjust for potential confounders. RESULTS: Matched UMEC/VI and TIO cohorts each included 7997 patients and were balanced on baseline characteristics (mean age 70.9 years; female 47.1-47.6%). Over 12 months, patients initiating UMEC/VI had significantly reduced risk (hazard ratio [95% CI]: 0.87 [0.79, 0.96]; p = 0.006) and rates (rate ratio [95% CI]: 0.80 [0.72, 0.92]; p = 0.008) of COPD-related inpatient admissions compared with TIO. While all-cause readmission rates were similar between treatment cohorts, readmission rates among patients with an initial admission length of stay of 1-3 days were numerically lower for UMEC/VI versus TIO (30-day readmissions: 10.5% vs. 12.4%; 90-day readmissions: 15.5% vs. 19.8%). Similar patterns were observed for COPD-related readmissions. CONCLUSIONS: These findings highlight the real-world benefits of dual therapy with UMEC/VI versus TIO in reducing inpatient admissions and readmissions in patients with COPD, which may translate to lower healthcare costs.

Patients with chronic obstructive pulmonary disease (COPD) who are admitted to the hospital are more likely to be readmitted in the future, have higher healthcare costs, and are more likely to die from their illness. Patients who are readmitted to hospital have even higher treatment costs. Identifying which treatments are best at reducing the number of patients with COPD who are admitted to the hospital may help to improve outcomes and reduce the cost of COPD treatment. We used US healthcare claims data to compare two daily treatments for COPD, umeclidinium/vilanterol and tiotropium. We aimed to find out which treatment was more effective at reducing hospital admissions due to COPD. We also compared how many patients on each treatment were readmitted within 30 or 90 days of their original hospital admission for COPD. We found that patients who started treatment with umeclidinium/vilanterol were less likely to be admitted to the hospital for COPD than patients who started treatment with tiotropium. Similar numbers of patients on each treatment were readmitted to the hospital within 30 or 90 days after they were discharged. However, among patients whose initial hospital stay was short (1­3 days), readmissions within 30 or 90 days were less common with umeclidinium/vilanterol than tiotropium. These findings suggest that umeclidinium/vilanterol may be more effective than tiotropium at reducing the number of patients with COPD who need to be admitted or readmitted to hospital. Starting COPD treatment with umeclidinium/vilanterol may lead to better health outcomes and lower costs than tiotropium.

Real-World Healthcare Resource Utilization in Patients with Classical Hodgkin Lymphoma Treated with Pembrolizumab and Nivolumab in the USA.

BACKGROUND: Patients with classical Hodgkin lymphoma (cHL) relapsed or refractory (R/R) disease who relapse after or are ineligible for autologous stem cell transplantation have a poor prognosis. Recently, the anti-PD1 monoclonal antibodies nivolumab and pembrolizumab were approved by the US Food and Drug Administration (FDA; May 2016 and March 2017, respectively) as treatment options for R/R cHL patients. OBJECTIVE: In the absence of comparative clinical trials between these agents, this observational study was conducted to evaluate the healthcare resource utilization (HRU) of patients with cHL initiated on pembrolizumab compared to nivolumab in the USA. PATIENTS AND METHOD: Healthcare insurance claims from Symphony Health's IDV® (Integrated Dataverse) (July 2014-June 2018) were used in this retrospective study. The study population included adult patients with cHL initiated on pembrolizumab or nivolumab (index date). Inverse probability of treatment weighting was used to adjust for differences in patient characteristics between cohorts. All-cause and cHL-related hospitalizations and outpatient visits were measured during the observation (post-index) period and reported per patient-year (PPY). Rates of HRU were compared between cohorts using rate ratios (RRs). RESULTS: A total of 92 and 218 patients initiated on pembrolizumab and nivolumab, respectively, were included in the study population. After weighting, the mean age was similar at 55 years in both cohorts, while the proportion of females was lower in the pembrolizumab cohort (35.3%) compared to the nivolumab cohort (44.1%). Mean Quan-Charlson Comorbidity Index score was well balanced after weighting in the pembrolizumab and nivolumab cohorts (4.2 and 4.3, respectively). During the observation period, patients in the pembrolizumab cohort had significantly lower rates of all-cause hospitalizations (RR [95% CI] 0.33 [0.09-0.80]) and cHL-related hospitalizations (RR [95% CI] 0.14 [0.02-0.37]) than those in the nivolumab cohort. Rates of all-cause and cHL-related outpatient visits were not statistically different between patients in the pembrolizumab and nivolumab cohorts. CONCLUSIONS: In this real-world study, adult cHL patients initiated on pembrolizumab had significantly lower rates of all-cause and cHL-related hospitalizations compared to patients initiated on nivolumab.

Cancer associated thrombosis and mortality in patients with cancer stratified by khorana score risk levels.

BACKGROUND: The Khorana score (KS) clinical algorithm is used to predict VTE risk in cancer patients. The study objective was to evaluate VTE and survival rates among patients newly diagnosed with cancer and stratified by KS in a real-world population. METHODS: Data from the Optum® Clinformatics® DataMart database between 01/01/2012-09/30/2017 was used to identify adults with ≥ 1 hospitalization or ≥ 2 outpatient claims with a cancer diagnosis (index date). Only patients who were initiated on chemotherapy or radiation therapy were included. Patients were classified based on KS (KS = 0, 1, 2 or ≥ 3). Time-to-first VTE and survival were evaluated from the index date to the earliest among end of data availability or insurance coverage, death, or 12 months post-index using Kaplan-Meier (KM) analyses. RESULTS: A total of 2,488 (KS = 0); 2,125 (KS = 1), 1,074 (KS = 2), and 507 (KS ≥ 3) cancer patients were included. The 12-month KM rates of VTE were 3.1%, 5.4%, 7.9%, and 14.9% (associated median time to VTE of 2.7, 3.0, 1.4, and 1.7 months) among KS = 0, 1, 2, and ≥ 3 cohorts, respectively. Corresponding adjusted hazard ratios (95% CIs) relative to the KS = 0 cohort were 1.72 (1.25-2.38), 2.46 (1.73-3.50), and 4.99 (3.40-7.31) for the KS = 1, 2, and ≥ 3 cohorts, respectively (all P < .001). Regardless of KS, patients with VTE had significantly lower survival rates than those without. CONCLUSIONS: This real-world claims-based cohort study of newly diagnosed cancer patients showed significantly higher rates of VTE with increased KS, confirming its predictive ability. Moreover, VTE was associated with lower survival rates within each KS cohort.

Healthcare costs of NVAF patients treated with rivaroxaban and apixaban in the US.

OBJECTIVES: To provide the most current assessment of real-world healthcare resource utilization (HRU) and costs among patients with non-valvular atrial fibrillation (NVAF) who newly initiated rivaroxaban and apixaban using a large US database. MATERIAL AND METHODS: A retrospective weighted cohort design was used with healthcare insurance claims from the Optum Clinformatics Data Mart databases (January 2012-December 2018). The index date was defined as the first dispensing of rivaroxaban or apixaban. Adult NVAF patients with an index date on or after 1 January 2016, ≥ 12 months of continuous eligibility before the index date and ≥ 1 month after, and without prior use of oral anticoagulant were included. The observation period spanned from the index date to the earliest of the end of data availability, end of insurance coverage, or death. Inverse probability of treatment weighting (IPTW) was used to adjust for differences in baseline characteristics between cohorts. All-cause healthcare resource utilization (HRU), including hospitalization, emergency room, and outpatient visits, and healthcare costs, including medical and pharmacy costs, were evaluated from the payer's perspective during the observation period up to 18 and 24 months, separately. RESULTS: In total, 23,822 rivaroxaban and 53,666 apixaban users were included. After weighting, all baseline characteristics were well balanced between cohorts (mean age: 73.8 years, female: 46.6% in both cohorts). Up to 18 months of follow-up, rivaroxaban users incurred significantly lower total healthcare costs compared to apixaban users (cost difference = -$1,121; p = 0.020), driven by significantly lower rates of outpatient hospital visits and associated costs (cost difference = -$1,579; p < 0.001). Similar results were found in the analysis conducted for up to 24 months of follow-up (total cost difference = ‒$1,111; p = 0.020). CONCLUSIONS: In this large retrospective analysis, patients with NVAF initiated on rivaroxaban incurred significantly lower healthcare costs compared to those initiated on apixaban, which were primarily driven by significantly lower outpatient visits and costs during the 18- and 24-month follow-up periods.

Ibuprofen rescues mutant cystic fibrosis transmembrane conductance regulator trafficking.

BACKGROUND: Small molecules as shown by VX809 can rescue the mislocalization of F508del-CFTR. The aim of this study was to identify correctors with a clinical history and their targets of action. METHODS: CFTR correctors were screened using two F508del-CFTR expressing cell based HTS assays. Electrophysiological studies using CFBE41o(-) and HBE cells and in-vivo mouse assays confirmed CFTR rescue. The target of action was attained using pharmacological inhibitors and siRNA to specific genes. RESULTS: Ibuprofen was identified as a CFTR corrector. Ibuprofen treatment of polarized CFBE41o(-) monolayers increased the short-circuit current (Isc) response to stimulation. In vivo CF mice treatment with ibuprofen restored the CFTR trafficking. SiRNA knock down of cyclooxygenase expression caused partial F508del-CFTR correction. CONCLUSION: These studies show that ibuprofen is a CFTR corrector and that it causes correction by COX-1 inhibition. Hence ibuprofen may be suitable to be part of a future CF combination therapy.