Ischemic stroke and systemic embolism among patients with non-valvular atrial fibrillation who abandon oral anticoagulant therapy.

OBJECTIVES: To compare the risk of stroke and systemic embolism (SE) among patients with nonvalvular atrial fibrillation (NVAF) who abandoned their first direct oral anticoagulant (DOAC) fill ("abandoners") relative to patients who continued DOACs beyond the first fill ("continuers"). METHODS: In this retrospective longitudinal study, adults with NVAF prescribed DOACs were selected from Symphony Health, an ICON plc Company, PatientSource, 1 April 2017 to 31 October 2020. A 90-day landmark period following the first DOAC fill was used to classify patients as abandoners or continuers. Inverse probability of treatment weighting was used to balance baseline characteristics between cohorts. Time to ischemic stroke/SE was described and compared between cohorts using weighted Kaplan-Meier and Cox proportional hazard models from the end of the landmark period until end of clinical activity or data. RESULTS: After weighting, 200,398 and 211,352 patients comprised the abandoner and continuer cohorts, respectively. The mean duration of follow-up was 14.9 and 15.7 months, respectively. At 12 months of follow-up, the probability of ischemic stroke/SE was 1.34% in the abandoner cohort and 1.00% in the continuer cohort; the risk of ischemic stroke/SE was 35% higher in the abandoner versus continuer cohort (hazard ratio [95% confidence interval] = 1.35 [1.20, 1.51]; p < 0.0001). CONCLUSIONS: Patients with NVAF who abandoned the first DOAC fill had significantly higher risk of ischemic stroke/SE compared to patients who continued therapy beyond the first fill. There is an unmet need for better access to DOACs so that the long-term risk of poor outcomes may be minimized.

Access and real-world use patterns of esketamine nasal spray among patients with treatment-resistant depression covered by private or public insurance.

OBJECTIVE: To describe access and real-world use patterns of esketamine nasal spray among adults with treatment-resistant depression (TRD) with private or public insurance. METHODS: Adults with ≥1 claim for esketamine nasal spray were selected from Clarivate's Real World Data product (January 2016-March 2021). Patients with evidence of TRD initiating esketamine (index date) after 05 March 2019 were included. Esketamine access, as measured by pharmacy claim approval rate for each treatment session, and use patterns were described post-index (follow-up period). RESULTS: Among 535 patients with pharmacy claims for esketamine nasal spray (mean age 49.1 years; 65.4% females), 534 had the first esketamine claim being a pharmacy claim, of which 34.6% were approved, 46.3% were rejected, and 19.1% were abandoned. Main reasons for rejection included "claim not covered by plan" (57.1%), "claim errors" (52.6%), and "prior authorization required" (22.7%). The approval rate increased to 85.2% by the second esketamine treatment session. A total of 273 patients initiated esketamine (mean age 49.3 years; 66.3% females). Patients had a mean ± standard deviation (SD) of 11.8 ± 13.3 esketamine sessions over a mean ± SD of 11.8 ± 6.4 months; 47.6% of patients completed ≥8 sessions (i.e. the number of sessions in induction phase) over a mean ± SD of 80.1 ± 71.9 days (per label, 28 days); 48 (17.6%) patients completed induction per label, and among them 93.8% continued treatment. CONCLUSIONS: Initial access to esketamine nasal spray may be hindered by prior authorization or claim filing errors. Among patients who initiated esketamine, treatment compliance generally deviates from label recommendations; yet, most of those who received induction per label successfully transition to maintenance with esketamine.

Esketamine nasal spray is a novel therapy for treatment-resistant depression (TRD). In the United States, insurance plans often regulate access to esketamine. Additionally, for patients, it may be challenging to comply to the treatment schedule, because patients must receive esketamine in a certified treatment center, be monitored for 2 h for potential side effects, and they cannot drive until the next day. This real-world study used insurance claims data and found that patients with TRD had difficulties accessing esketamine. Among those with access, esketamine use patterns were suboptimal.

Weight and BMI Changes Following Initiation of Emtricitabine/Tenofovir Alafenamide Co-Formulated with Darunavir or Co-Administered with Dolutegravir in Overweight or Obese, ART-Naïve People Living with HIV-1.

Introduction: Integrase strand transfer inhibitor-based regimens (eg, containing dolutegravir [DTG]) are associated with weight/body mass index (BMI) increases among people living with HIV-1 (PLWH). Assessing antiretroviral therapy (ART)-related weight/BMI changes is challenging, as PLWH may experience return-to-health weight gain as a result of viral suppression. This retrospective, longitudinal real-world study compared weight/BMI outcomes among overweight/obese (BMI ≥25 kg/m2; thus excluding return-to-health weight/BMI changes), treatment-naïve PLWH who initiated darunavir (DRV)/cobicistat (c)/emtricitabine (FTC)/tenofovir alafenamide (TAF) or DTG + FTC/TAF. Methods: Treatment-naïve PLWH with BMI ≥25 kg/m2 who initiated DRV/c/FTC/TAF or DTG + FTC/TAF (index date) had ≥12 months of baseline observation and ≥1 weight/BMI measurement in baseline and post-index periods in the Symphony Health IDV® database (07/17/2017-12/31/2021) were included. Inverse probability of treatment weighting (IPTW) was used to balance differences in baseline characteristics between cohorts. On-treatment time-to-weight/BMI increases ≥5% were compared between cohorts using weighted adjusted Cox models. Results: Post-IPTW, 76 overweight/obese DRV/c/FTC/TAF-treated (mean age = 51.2 years, 30.7% female, 35.6% Black, mean baseline BMI = 33.2 kg/m2) and 88 overweight/obese DTG + FTC/TAF-treated PLWH (mean age = 51.5 years, 31.4% female, 31.4% Black, mean baseline BMI = 32.7 kg/m2) were included. The median [interquartile range] time from ART initiation to weight/BMI increase ≥5% was shorter for the DTG + FTC/TAF cohort (21.8 [9.9, 32.3] months) than the DRV/c/FTC/TAF cohort (median and interquartile times not reached; Kaplan-Meier rate at 21.8 months = 20.8%). Over the entire follow-up, overweight/obese PLWH initiating DTG + FTC/TAF had a more than twofold greater risk of experiencing weight/BMI increase ≥5% compared to those initiating DRV/c/FTC/TAF (hazard ratio [95% confidence interval]=2.43 [1.02; 7.04]; p = 0.036). Conclusion: Overweight/obese PLWH who initiated DTG + FTC/TAF had significantly greater risk of weight/BMI increase ≥5% compared to similar PLWH who initiated DRV/c/FTC/TAF and had shorter time-to-weight/BMI increase ≥5%, suggesting a need for additional monitoring to assess the risk of weight gain-related cardiometabolic disease.

Incidence of cardiometabolic outcomes among people living with HIV-1 initiated on integrase strand transfer inhibitor versus non-integrase strand transfer inhibitor antiretroviral therapies: a retrospective analysis of insurance claims in the United States.

INTRODUCTION: Integrase strand transfer inhibitor (INSTI)-containing antiretroviral therapy (ART) has been associated with weight gain, though there is limited information on associations between ART-related weight gain and cardiometabolic outcomes among people living with HIV-1 (PLWH). We, therefore, evaluated risks of incident cardiometabolic outcomes following INSTI versus non-INSTI-based ART initiation in the United States. METHODS: We conducted a retrospective study using IBM MarketScan Research Databases (12 August 2012-31 January 2021). Treatment-naïve PLWH initiating ART (index date) on/after 12 August 2013 (approval date of the first second-generation INSTI, dolutegravir) were included and censored at regimen switch/discontinuation, end of insurance eligibility or end of data availability. We used inverse probability of treatment weights constructed with baseline (12 months pre-index) characteristics to account for differences between INSTI- and non-INSTI-initiating cohorts. Doubly robust hazard ratios (HRs) obtained from weighted multivariable Cox regression were used to compare time to incident cardiometabolic outcomes (congestive heart failure [CHF], coronary artery disease, myocardial infarction, stroke/transient ischemic attack, hypertension, type II diabetes, lipid disorders, lipodystrophy and metabolic syndrome) by INSTI-initiation status. RESULTS: Weighted INSTI (mean age = 39 years, 23% female, 70% commercially insured, 30% Medicaid insured) and non-INSTI (mean age = 39 years, 24% female, 71% commercially insured, 29% Medicaid insured) cohorts included 7059 and 7017 PLWH, respectively. The most common INSTI-containing regimens were elvitegravir-based (43.4%), dolutegravir-based (33.3%) and bictegravir-based (18.4%); the most common non-INSTI-containing regimens were darunavir-based (31.5%), rilpivirine-based (30.4%) and efavirenz-based (28.3%). Mean±standard deviation follow-up periods were 1.5±1.5 and 1.1±1.2 years in INSTI- and non-INSTI-initiating cohorts, respectively. INSTI initiators were at a clinically and significantly increased risk of experiencing incident CHF (HR = 2.12, 95% confidence interval [CI] = 1.08-4.05; p = 0.036), myocardial infarction (HR = 1.79, 95% CI = 1.03-5.65; p = 0.036) and lipid disorders (HR = 1.26, 95% CI = 1.04-1.58; p = 0.020); there was no evidence of an increased risk for other individual or composite outcomes. CONCLUSIONS: Over a short average follow-up period of <2 years, INSTI use among treatment-naïve PLWH was associated with an increased risk of several cardiometabolic outcomes, such as CHF, myocardial infarction and lipid disorders, compared to non-INSTI use. Further research accounting for additional potential confounders and with longer follow-up is warranted to more accurately and precisely quantify the impact of INSTI-containing ART on long-term cardiometabolic outcomes.

Esketamine nasal spray for major depressive disorder with acute suicidal ideation or behavior: description of treatment access, utilization, and claims-based outcomes in the United States.

AIMS: To describe real-world esketamine nasal spray access and use as well as healthcare resource use (HRU) and costs among adults with evidence of major depressive disorder (MDD) with suicidal ideation or behavior (MDSI). METHODS: Adults with ≥1 claim for esketamine nasal spray and evidence of MDSI 12 months before/on the date of esketamine initiation (index date) were selected from Clarivate's Real World Data product (01/2016-03/2021). Patients initiated esketamine on/after 03/05/2019 (esketamine approval for treatment-resistant depression; later approved for MDSI on 08/05/2020) were included in the overall cohort. Esketamine access (measured as approved/abandoned/rejected claims) and use were described post-index; HRU and healthcare costs (2021 USD) were described over 6 months pre- and post-index. RESULTS: Among 269 patients in the overall cohort with esketamine pharmacy claims, 46.8% had the first pharmacy claim approved, 38.7% had it rejected, and 14.5% abandoned their claim; 169 patients were initiated on esketamine in the overall cohort (mean age 40.9 years, 62.1% female); 45.0% had ≥8 esketamine treatment sessions (recommended per label) with a mean [median] of 85.0 [58.5] days from index to 8th session (per label 28 days). Among 115 patients with ≥6 months of data post-index, in the 6-month pre- and post-index, respectively, 37.4 and 19.1% had all-cause inpatient admissions, 42.6 and 33.9% had emergency department visits, 92.2 and 81.7% had outpatient visits; mean ± standard deviation all-cause monthly total healthcare costs were $8,371±$15,792 and $6,486±$7,614, respectively. LIMITATIONS: This was a descriptive claims-based analysis; no formal statistical comparisons were performed due to limited sample size as data covered up to 24 months of esketamine use in the US clinical setting. CONCLUSIONS: Nearly half of patients experience access issues with first esketamine nasal spray treatment session. All-cause HRU and healthcare costs trend lower in the 6 months after relative to 6 months before esketamine initiation.

Major depressive disorder (MDD), or clinical depression, can sometimes be accompanied by preoccupation with suicide along with suicidal behavior. Patients diagnosed with MDD with suicidal ideation or behavior (MDSI) can vary in their reactions to this condition, and some never seek treatment. This study investigated treatment patterns in real-world clinics of a recently approved nasal spray therapy, esketamine, which helps improve depressive symptoms in patients with MDSI. The study results highlight challenges related to esketamine treatment access, particularly for the first treatment session. Still, healthcare resource utilization and healthcare costs trended lower following treatment initiation with esketamine in MDSI, suggesting the potential benefits of esketamine in mitigating the clinical and economic burden of MDSI among those who gain access to the drug. Streamlining the approval process by health plan providers to remove hindrances related to compliance with plan requirements may ensure more timely access to esketamine for MDSI.

Venous thromboembolism recurrence among one-and-done direct oral anticoagulant users: a retrospective longitudinal study.

BACKGROUND: Direct oral anticoagulants (DOACs) are the American Society of Hematology guideline-recommended treatment for venous thromboembolism (VTE) in the United States (US). AIM: To compare risk of VTE recurrence between patients who, following the first fill, discontinued ("one-and-done") versus those who continued ("continuers") DOACs. METHOD: Open source US insurance claims data (04/1/2017 to 10/31/2020) were used to select adult patients with VTE initiated on DOACs (index date). Patients with only one DOAC claim during the 45-day landmark period (starting on the index date) were classified as one-and-done and the remaining as continuers. Inverse probability of treatment weighting was used to reweight baseline characteristics between cohorts. VTE recurrence based on the first post-index deep vein thrombosis or pulmonary embolism event was compared using weighted Kaplan-Meier and Cox proportional hazard models from landmark period end to clinical activity or data end. RESULTS: 27% of patients initiating DOACs were classified as one-and-done. After weighting, 117,186 and 116,587 patients were included in the one-and-done and continuer cohorts, respectively (mean age 60 years; 53% female; mean follow-up 15 months). After 12 months of follow-up, the probability of VTE recurrence was 3.99% and 3.36% in the one-and-done and continuer cohorts; the risk of recurrence was 19% higher in the one-and-done cohort (hazard ratio [95% confidence interval] = 1.19 [1.13, 1.25]). CONCLUSION: Substantial proportion of patients discontinued DOAC therapy after the first fill, which was associated with significantly higher risk of VTE recurrence. Early access to DOACs should be encouraged to reduce the risk of VTE recurrence.

Ischemic Stroke and Systemic Embolism Among One-and-Done Direct Oral Anticoagulant Users with Non-valvular Atrial Fibrillation.

INTRODUCTION: Direct oral anticoagulants (DOACs) are essential in ischemic stroke/systemic embolism (SE) prevention among patients with nonvalvular atrial fibrillation (NVAF). This study compared the risk of ischemic stroke/SE among patients with NVAF who discontinued DOACs following the first fill ("one-and-done") relative to patients who continued DOACs beyond the first fill ("continuers"). METHODS: De-identified data from Symphony Health, an ICON plc Company, PatientSource®, April 1, 2017 to October 31, 2020, were used to identify adults with NVAF initiated on DOACs (index date). Patients with only one DOAC claim during the 90-day landmark period starting on the index date were classified as one-and-done and the remaining as continuers. Inverse probability of treatment weighting was used to balance baseline characteristics in the cohorts. Time from the landmark period end to the first ischemic stroke/SE event or, among those without the event, to clinical activity or data end was compared between balanced cohorts using survival analysis. RESULTS: Of patients initiating DOACs, 23.6% were classified as one-and-done users. After weighting was performed, 241,159 and 238,889 patients comprised the one-and-done and continuer cohorts, respectively. At 12 months of follow-up, the probability of ischemic stroke/SE was 1.44% in the one-and-done cohort and 1.00% in the continuer cohort [hazard ratio (95% confidence interval) 1.44 (1.34-1.54); p < 0.0001]. Results at earlier and later time points and in a sensitivity analysis with a 75-day landmark period were similar. CONCLUSION: A substantial proportion of patients were one-and-done DOAC users, which was associated with significantly higher risk of ischemic stroke/SE events. There is an unmet need to improve access and encourage continuous use of DOACs among patients with NVAF so that severe and fatal complications may be mitigated.

Venous Thromboembolism Recurrence Among Patients Who Abandon Oral Anticoagulant Therapy in the USA: A Retrospective Longitudinal Study.

INTRODUCTION: Among patients with venous thromboembolism (VTE), direct oral anticoagulants (DOACs) are recommended for preventing thromboembolic recurrence, complications, and mortality. This study compared the risk of VTE recurrence among patients who abandoned their first DOAC fill ("abandoners") relative to patients who did not ("non-abandoners"). METHODS: Adults with VTE who were prescribed DOACs were selected from Symphony Health, an ICON plc Company, PatientSource®, April 1, 2017 to October 31, 2020. Patients who abandoned their first (index) DOAC fill were classified as abandoners and patients with an approved index DOAC fill as non-abandoners. Baseline characteristics were balanced between cohorts using inverse probability of treatment weighting. VTE recurrence based on the first post-index VTE event (deep vein thrombosis or pulmonary embolism) was ascertained and compared between cohorts using weighted Kaplan-Meier and Cox proportional hazard models during the follow-up period (i.e., index DOAC fill date to end of clinical activity or data availability). RESULTS: After weighting, 152,443 and 153,931 patients comprised the abandoner and non-abandoner cohorts, respectively (mean age 60 years; 53% female; mean follow-up duration 15 months). After 3 months of follow-up, the probability of VTE recurrence was 7.74% in the abandoner cohort and 4.65% in the non-abandoner cohort; the risk of recurrence was 72% higher in the abandoner versus non-abandoner cohort (hazard ratio [95% confidence interval] 1.72 [1.64, 1.82]; p < 0.0001). At 12 months, the probability of recurrence was 9.91% in the abandoner cohort and 6.89% in the non-abandoner cohort; the risk of recurrence was 53% higher in the abandoner versus non-abandoner cohort (1.53 [1.46, 1.61]; p < 0.0001). CONCLUSION: Patients abandoning the first DOAC fill had significantly higher risk of VTE recurrence compared to patients who did not abandon the first fill. Ensuring proper access and encouraging early and continuous use of DOACs may help prevent severe and fatal complications among patients with VTE.