OBJECTIVETo estimate long-term persistence among bio-naïve patients with CD initiated on ustekinumab or adalimumab. METHODSAdults with CD initiating ustekinumab or adalimumab (index date, between ...September 23, 2016 and August 1, 2019) were sampled from the IBM MarketScan Commercial Database. Patients without CD-indicated biologics (bio-naïve) and with no diagnoses for other autoimmune diseases 12 months pre-index date (baseline) were included. Cohorts were balanced on baseline characteristics with inverse probability of treatment weighting. Persistence was defined as the absence of therapy exposure gaps >120 days (ustekinumab) or >60 (adalimumab) between days of supply. Composite endpoints were persistence and being corticosteroid-free (no corticosteroids >14 days of supply after day 90 post-index) and persistence while on monotherapy (no immunomodulators/non-index biologics). Persistence was analyzed using Kaplan-Meier and Cox's models. RESULTSUstekinumab and adalimumab cohorts included 671 and 2,975 patients. At 12 months post-index, ustekinumab patients were significantly more persistent (hazard ratio HR = 1.60; 95% confidence interval CI = 1.33-1.93), persistent while on monotherapy (HR = 1.43; 95% CI = 1.24-1.65), and trended toward being more persistent and corticosteroid-free (HR = 1.14; 95% CI = 0.99-1.30) vs adalimumab. At 24 months post-index, ustekinumab patients were significantly more persistent (HR = 1.66; 95% CI = 1.40-1.97), persistent while on monotherapy (HR = 1.44; 95% CI = 1.26-1.64), and persistent and corticosteroid-free (HR = 1.15; 95% CI = 1.01-1.31) vs adalimumab. CONCLUSIONSBio-naïve patients with CD initiated on ustekinumab demonstrated significantly more persistence than patients initiated on adalimumab at 12 and 24 months of treatment. Long-term persistence is a measure of a drug's real-world performance and findings may aid clinical decision-making.
OBJECTIVESTo 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"). METHODSIn 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. RESULTSAfter 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). CONCLUSIONSPatients 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.
To compare health care resource utilization (HRU) and costs among commercially insured patients with nasal polyposis (NP) with and without recurrence after endoscopic sinus surgery (ESS).
...Retrospective matched cohort study.
Adults with initial ESS or an NP excision after a new NP diagnosis were identified in Optum's Clinformatics Data Mart Database (October 1, 2014-December 31, 2019).
The index date was the date of NP recurrence, identified with a claims-based algorithm for the recurrent cohort, or a random date for the nonrecurrent cohort. Patients in both cohorts were matched 1:1 on baseline characteristics (12 months preindex) via propensity scores and exact matching factors. Annual HRU and costs (2019 US$) were compared between the matched cohorts at 12 months postindex.
NP recurrence was identified among 3343 of 16,693 patients with initial ESS; after matching, each cohort comprised 1574 patients (median age, 54 years; 40% female) with similar baseline health care costs (recurrent, $34,420; nonrecurrent, $33,737). At 12 months postindex, the recurrent cohort had higher HRU, including 36% and 51% more outpatient and emergency department visits, respectively (all P < .01). Mean health care costs were $9676 higher in the recurrent cohort ($24,039) relative to the nonrecurrent cohort ($14,363, P < .01). The mean cost difference between cohorts was driven by $8211 in additional outpatient costs, as well as $6062 in additional NP-related outpatient costs, in the recurrent cohort (all P < .01).
NP recurrence is associated with a substantial economic burden, which appears to be driven by outpatient services.
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.
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.
To compare persistence and describe dose titration among bio-naïve patients with Crohn's disease (CD) initiated on ustekinumab or adalimumab.
Bio-naïve adults with CD who initiated ustekinumab or ...adalimumab (index date) from 23 September 2016 (ustekinumab US approval for CD) to 1 August 2019 were selected from IQVIA PharMetrics Plus. Cohorts were balanced on baseline characteristics measured over 12 months pre-index using inverse probability of treatment weights. Persistence was defined as no gaps (ustekinumab: >120 days; adalimumab: >60 days) between days of supply. Dose escalation was defined as ≥2 consecutive sub-cutaneous claims 100% above the US label daily dose in the maintenance phase; de-escalation was a return to the daily dose for ≥2 consecutive claims. Outcomes were described using weighted Kaplan-Meier models; persistence outcomes were compared using Cox's proportional hazards models.
At 12 months post-index, patients in the ustekinumab (n = 948) versus adalimumab (n = 4143) cohort had a significantly higher rate of persistence on index biologic (hazard ratio HR 1.50; 95% confidence interval CI: 1.29-1.74). A total of 830 (87.6%) patients in the ustekinumab cohort and 3713 (89.6%) in the adalimumab cohort began the maintenance phase; within 12 months, 11.2% and 16.9%, underwent a dose escalation, and 26.6% and 6.3%, respectively, subsequently de-escalated to the per US label daily exposure.
Bio-naïve patients with CD initiated on ustekinumab were more persistent than patients initiated on adalimumab; moreover, these patients had numerically lower dose escalation and higher de-escalation rates than patients initiated on adalimumab. Findings support the use of ustekinumab as a first-line treatment for bio-naïve patients with CD.
To describe real-world use of esketamine (ESK) intranasal spray and healthcare outcomes among patients with treatment-resistant depression (TRD) in the United States (US).
Adults with TRD initiated ...on ESK (index date) between 5 March 2019 (US approval date for TRD) and 31 October 2020 were sampled from IBM MarketScan Research Databases. TRD was defined as claims for ≥2 unique antidepressants during the same major depressive episode. Subgroups of the TRD cohort with comorbid cardiometabolic conditions, pain, anxiety disorder, and substance use disorder (SUD) were identified. Patients had ≥6 months of continuous health plan eligibility pre- and post-index.
The TRD cohort comprised 269 patients; comorbidity subgroups included 123 (cardiometabolic), 144 (pain), 189 (anxiety disorder), and 58 (SUD) patients. Proportion of patients completing ≥8 ESK sessions (number of sessions in induction phase) was 61.3% in the TRD cohort and ranged from 60.2% (cardiometabolic subgroup) to 72.4% (SUD subgroup) in subgroups. Median frequency of induction sessions was every 5-8 days among the TRD cohort and subgroups. Mean mental health-related inpatient costs reduced from pre- to post-index periods in the TRD cohort (mean ± standard deviation median costs per-patient-per-6-months: $3,480 ± $13,328 $0 pre-ESK initiation; $3,262 ± $16,666 $0 post-ESK initiation; mean difference: -$218) and subgroups (largest decrease in cardiometabolic subgroup: $4,864 ± $14,271 $0; $2,792 ± $15,757 $0; -$2,072). Mean mental health-related emergency department (ED) costs decreased in the TRD cohort ($608 ± $2,525 $0; $269 ± $1,143 $0; -$339) and subgroups (largest decrease in the SUD subgroup: $1,403 ± $3,752 $0; $351 ± $868 $0; -$1,052).
This is a descriptive analysis; sample size for some comorbidity subgroups is small.
The majority of patients completed ESK induction phase, and most dosing intervals were longer than the label recommendation. In this descriptive analysis, mental health-related inpatient and ED costs trended lower post-ESK initiation.
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.
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.
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).
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.
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.
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.
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.
