Treatment Patterns, Acute Healthcare Resource Use, and Costs of Patients with Treatment-Resistant Depression Completing Induction Phase of Esketamine in the United States.

BACKGROUND: This study aimed to understand treatment patterns, acute healthcare use, and cost patterns among adults with treatment-resistant depression (TRD) who completed induction treatment with esketamine nasal spray in the United States (US). Per label, induction is defined as administration twice a week for 4 weeks, after which maintenance is started on a weekly basis for 4 weeks, and thereafter, patients are treated weekly or bimonthly. METHODS: Adults with one or more esketamine claim (index date) on or after March 5, 2019 were selected from Optum's de-identified Clinformatics® Data Mart Database (January 2016-June 2022). Before the index date, patients had evidence of TRD and ≥ 12 months of continuous insurance eligibility (baseline period). Patients with eight or more esketamine treatment sessions were included in the main cohort. A subgroup included patients with one or more baseline mental health (MH)-related inpatient (IP) admission or emergency department (ED) visit (i.e., prior acute healthcare users). Treatment patterns were described during the follow-up period (index date until earliest of end of insurance eligibility or data); acute healthcare (i.e., IP and ED) resource use and costs (2021 US dollars) were reported during the baseline and follow-up periods. RESULTS: Of the 322 patients in the main cohort, 111 comprised the subgroup of prior acute healthcare users. During the follow-up period, mean time from index date to eighth esketamine session was 73.2 days in the main cohort and 78.8 days in the subgroup (per label, 28 days). Further, 75.2% of the main cohort and 73.9% of the subgroup completed four or more esketamine maintenance sessions following induction. In the main cohort, mean all-cause acute healthcare costs per patient per month (PPPM) decreased from baseline ($837) to follow-up ($770). Similar reductions were observed for mean MH-related acute healthcare costs PPPM (baseline $648, follow-up $577). In the subgroup, mean all-cause acute healthcare costs PPPM also decreased (baseline $2323, follow-up $1423), driven by mean MH-related acute healthcare costs PPPM (baseline $1880, follow-up $1139). Mean all-cause acute healthcare use per ten patients per month remained largely stable from baseline to follow-up in the main cohort (IP days: baseline 2.24, follow-up 2.13; ED visits: baseline 1.33, follow-up 1.45) and decreased in the subgroup (IP days: baseline 6.38, follow-up 4.56; ED visits: baseline 2.58, follow-up 2.41). Trends in mean MH-related acute healthcare use were similar. CONCLUSION: Patients generally required more time than label recommendation to complete esketamine induction treatment, and most went on to have 12 or more esketamine sessions. Completion of induction treatment correlated with reductions in mean all-cause and MH-related acute healthcare costs. Larger reductions were seen in the subgroup of prior acute healthcare users.

Economic burden of generalized myasthenia gravis (MG) in the United States and the impact of common comorbidities and acute MG-events.

BACKGROUND: This study assessed the incremental healthcare costs and resource utilization (HRU) associated with generalized myasthenia gravis (gMG), as well as variability in these outcomes among patients with gMG and common comorbidities and acute MG-related events. METHODS: Adults with gMG and without MG were identified from a large US database (2017-2021). The index date was the first MG diagnosis (gMG cohort) or random date (non-MG cohort). Cohorts were propensity score matched 1:1. The gMG cohort included subgroups of patients with a 12-month pre-index (baseline) cardiometabolic or psychiatric comorbidity, or a post-index MG exacerbation/crisis. Monthly healthcare costs (2021 USD) and HRU were compared post-index between gMG and non-MG cohorts. RESULTS: The gMG and matched non-MG cohorts each contained 2,739 patients. Mean incremental healthcare costs associated with MG were $4,155 (gMG: $5,567; non-MG: $1,411), with differences driven by incremental inpatient costs of $2,166 (gMG: $2,617; non-MG: $452); all p < 0.001. The gMG versus non-MG cohort had 4.36 times more inpatient admissions and 2.26 times more outpatient visits; all p < 0.001. Among patients with gMG in cardiometabolic (n = 1,859), psychiatric (n = 1,308), and exacerbation/crisis (n = 419) subgroups, mean monthly healthcare costs were $6,660, $7,443, and $17,330, respectively. CONCLUSIONS: gMG is associated with substantial incremental costs and HRU, with inpatient costs driving the total incremental costs. Costs increased by 20% and 34% among patients with cardiometabolic and psychiatric conditions, respectively, and over three times among those with acute MG-related events. gMG is a complex disease requiring management of comorbidities and treatment options that can prevent acute symptomatic events.

Generalized myasthenia gravis (gMG) is a rare long-standing condition that affects the junctions between nerves and muscles, causing them to be weak. In a serious case, the diaphragm ­ a muscle that helps with breathing ­ becomes so weak that a patient will need a machine to breathe for them. This is called MG exacerbation or crisis. In this study, we used a large insurance database in the United States to look at how much money healthcare payers paid for gMG patients on average and what healthcare resources patients with gMG used. We compared these findings with patients without gMG. Also, among patients with gMG, we reported these findings specifically for patients who also had heart, blood, or blood vessel disease; patients who had a mental illness; and patients who had MG exacerbation or crisis later on. We found that patients with gMG used $5,567 per month on average ($4,155 more than patients without gMG), mostly from overnight hospital stays. Patients with gMG also had four times more overnight hospital stays and two times more hospital day visits when we compared them to patients without gMG. Patients with gMG and other health conditions used even more money and resources per month. Patients with MG exacerbation or crisis used $17,330 per month on average. Our results showed that gMG led to higher healthcare cost and resource use. In order to reduce cost and resources, doctors also need to control for other health conditions as they treat patients with gMG, and to prevent patients from having MG exacerbation or crisis later on.

Burden of chronic corticosteroid use among patients with ulcerative colitis initiated on targeted treatment or conventional therapy in the United States.

BACKGROUND: Chronic corticosteroid use is common in ulcerative colitis (UC); however, real-world evidence of its burden to the health care system is limited. OBJECTIVE: To quantify chronic corticosteroid use burden in UC. METHODS: Adults with UC initiated on targeted treatments (ie, biologics and advanced/small molecule therapies) or conventional therapy (index date) were selected from a deidentified US insurance claims database (January 1, 2004, to September 30, 2021). Targeted treatments and conventional therapy initiators were stratified into chronic (>90 days corticosteroid use 12 months post-index [landmark]) and nonchronic corticosteroid users. Patient characteristics 12 months pre-index were balanced with inverse probability of treatment weighting. Health care resource use, costs (US$ 2021), and corticosteroid-related complications were compared in the 12 months post-landmark. RESULTS: Targeted treatment initiators included 1,886 chronic and 1,911 nonchronic corticosteroid users; conventional therapy initiators included 4,980 chronic and 5,199 nonchronic users. Chronic vs nonchronic users had 94% more inpatient days and 16% more outpatient visits among targeted treatment initiators, and 135% more inpatient days and 30% more outpatient visits among conventional therapy initiators (all P < 0.01). Mean all-cause total costs per patient per year were $73,491 for chronic vs $58,884 for nonchronic users ($14,607 higher; P < 0.01) for targeted treatment initiators, and $39,335 for chronic vs $21,271 for nonchronic users ($18,065 higher; P < 0.01) for conventional therapy initiators. Odds of infection and bone loss were 14% and 113% higher, respectively, in chronic vs nonchronic users among targeted treatment initiators and 29% and 47% higher in chronic vs nonchronic users among conventional therapy initiators (all P < .01). CONCLUSIONS: The results of this study suggest that chronic corticosteroid use is associated with substantial clinical and economic burden and may indicate unmet needs in the management of UC progression.

Economic and clinical burden of chronic corticosteroid use in patients with Crohn[apos]s disease initiated on biologic or conventional therapies in the US: A retrospective claims study.

BACKGROUND: Chronic corticosteroid (CS) use is associated with complications, but estimates of the economic and clinical burden in patients with Crohn's disease (CD) are lacking. OBJECTIVE: To estimate the burden of chronic CS use in CD in the United States in terms of health care resource utilization (HRU), health care costs, and CS-related complications. METHODS: This was a retrospective study of adults with CD initiated on biologics or conventional therapies (index date). Patients from a deidentified insurance claims database (2004-2021) were classified as chronic CS users (>90 days of CS use) or nonchronic CS users based on a 12-month landmark period starting on the index date. Patient baseline characteristics were balanced, and outcomes (HRU, costs [2021 US dollars], and CS-related complications) 12 months after the landmark period were compared between CS groups using regressions with nonparametric bootstrap resampling to estimate confidence intervals and P values. RESULTS: Biologic initiators (mean age: 44 years, 55% female) included 3366 chronic and 3401 nonchronic CS users; conventional therapy initiators (mean age: 51 years, 59% female) included 3657 chronic and 3727 nonchronic CS users. Compared with nonchronic users, chronic users had significantly more inpatient days and outpatient visits (biologic initiators: 37% and 24% more, respectively; conventional therapy initiators: 36% and 17%, respectively; all P<0.05). Chronic users also had significantly higher mean all-cause total costs per-patient-per year (biologic: $72,967 vs. $63,100, mean cost difference [MCD] = $9867; conventional therapy: $40,144 vs. $26,426, MCD = $13,718; all P<0.001), as well as higher odds of infection (biologic: 14% higher; conventional therapy: 20% higher) and bone loss (63% and 41%, respectively) (all P<0.05). CONCLUSION: Chronic CS use in patients with CD is associated with a significant economic and clinical burden including higher HRU, health care costs, and prevalence of complications, suggesting unmet needs in the clinical management of this population.

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.

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.

Treatment patterns, healthcare utilization, and costs of patients with treatment-resistant depression initiated on esketamine intranasal spray and covered by US commercial health plans.

AIMS: 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). METHODS: 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. RESULTS: 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). LIMITATIONS: This is a descriptive analysis; sample size for some comorbidity subgroups is small. CONCLUSIONS: 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.

Economic Burden Associated With Nasal Polyposis Recurrence Among Commercially Insured Patients in the United States.

OBJECTIVE: 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). STUDY DESIGN: Retrospective matched cohort study. SETTING: 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). METHODS: 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. RESULTS: 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). CONCLUSION: NP recurrence is associated with a substantial economic burden, which appears to be driven by outpatient services.

Excess healthcare resource utilization and healthcare costs among privately and publicly insured patients with major depressive disorder and acute suicidal ideation or behavior in the United States.

BACKGROUND: This study assessed the healthcare resource utilization (HRU) and cost burden of patients with major depressive disorder (MDD) and acute suicidal ideation or behavior (SIB; MDSI) versus those with MDD without SIB and those without MDD. METHODS: Adults were selected from the MarketScan® Databases (10/2015-02/2020). The MDSI cohort received an MDD diagnosis within 6 months of a claim for acute SIB (index date). The index date was a random MDD claim in the MDD without SIB cohort and a random date in the non-MDD cohort. Patients had continuous eligibility ≥12 months pre- and ≥1 month post-index. HRU and costs were compared during 1- and 12-month post-index periods between MDSI and control cohorts matched 1:1 on demographics. RESULTS: The MDSI cohort included 73,242 patients (mean age 35 years, 60.6% female, 37.2% Medicaid coverage). At 1 month post-index, the MDSI cohort versus the MDD without SIB/non-MDD cohorts had 12.8/67.2 times more inpatient admissions and 3.3/8.9 times more emergency department visits; they had 2.9 times more outpatient visits versus the non-MDD cohort (all p < 0.001). The MDSI cohort had incremental mean healthcare costs of $5255 and $6674 per-patient-month versus the MDD without SIB and non-MDD cohorts (all p < 0.001); inpatient costs drove up to 89.5% of incremental costs. At 12 months post-index, HRU and costs remained higher in MDSI versus control cohorts. LIMITATIONS: SIB are underreported in claims; unobserved confounders may cause bias. CONCLUSIONS: MDSI is associated with substantial excess healthcare costs driven by inpatient costs, concentrated in the first month post-index, and persisting during the following year.

Economic Burden of Commercially Insured Patients With Major Depressive Disorder and Acute Suicidal Ideation or Behavior in the United States.

Objective: Suicidal ideation or behavior (SIB) is a symptom of major depressive disorder (MDD). This study evaluated health care resource utilization (HRU) and costs of commercially insured adults who had diagnosed MDD with acute SIB (MDSI).Methods: Adults with MDSI (index date: first SIB claim) and controls without MDD or suicide-related claims (random index date) were identified using International Classification of Diseases, Clinical Modification, 10th Revision codes in the OptumHealth Care Solutions, Inc. database (October 2014 to March 2017). Adults with < 12 months of plan enrollment pre-index and/or selected psychiatric comorbidities were excluded. MDSI and control cohorts were matched 1:1 on demographics and comorbidities. HRU and costs were compared between matched cohorts during up to 1 and 12 months post-index (inclusive) using regressions adjusted for baseline costs.Results: Among patients with MDSI (n = 1,576, mean age = 34 years, 55.6% female), most index events occurred in emergency department (ED; 50.7%) and inpatient (45.2%) settings. The MDSI cohort, compared with the control cohort within 1 and 12 months post-index, respectively, had 157.7 and 28.0 times more inpatient admissions, 16.4 and 5.4 times more ED visits, and 4.9 and 3.2 times more outpatient visits (all P < .01). Incremental health care costs per patient per month in the MDSI compared with the control cohort within 1 and 12 months were $7,839 and $2,757, respectively (both P values < .01). Inpatient and ED costs constituted 70.6% and 16.5% of the total incremental costs, respectively, within the first month of follow-up.Conclusions: Among commercially insured adults, MDSI was associated with significant economic burden; inpatient and ED services drove incremental costs of the condition. Further assessment of treatment options for this vulnerable patient population is warranted.

Health care resource use, short-term disability days, and costs associated with states of persistence on antidepressant lines of therapy.

AIMS: To compare health care resource utilization (HCRU), short-term disability days, and costs between states of persistence on antidepressant lines of therapy after evidence of treatment-resistant depression (TRD). METHODS: Patients with major depressive disorder (MDD) were identified in the IBM MarketScan Commercial and Medicare Supplemental Databases (01/01/2013-03/04/2019), Multi-State Medicaid Database (01/01/2013-12/31/2018), and Health Productivity Management Database (01/01/2015-12/31/2018). The index date was the date of the first evidence of TRD during the first observed major depressive episode. The follow-up period was divided into 45-day increments and categorized into persistence states: (1) evaluation (first 45 days after evidence of TRD); (2) persistence on the early line after evidence of TRD; (3) persistence on a late line; and (4) non-persistence. HCRU, short-term disability days, and costs were compared between persistence states using multivariate generalized estimating equations. RESULTS: Among 10,053 patients with TRD, the evaluation state was associated with higher likelihood of all-cause inpatient admissions (odds ratio [OR; 95% confidence interval (CI)] = 1.79 [1.49, 2.14]), emergency department visits (OR [95% CI] = 1.23 [1.12, 1.34]), and outpatient visits (OR [95% CI] = 3.83 [3.51, 4.18]; all p < .001) versus persistence on the early-line therapy. This resulted in $374 higher mean PPPM all-cause health care costs (95% CI = 265, 470; p < .001) during evaluation versus persistence on the early line therapy. The evaluation state was associated with 89% more short-term disability days (OR [95% CI] = 1.89 [1.49, 2.57] and $212 higher mean PPPM short-term disability costs (95% CI = 64, 259) relative to persistence on the early line (both p < .001). Moreover, during persistence on a later line, mean PPPM all-cause health care costs were $141 higher (95% CI = 13, 242; p = .028) relative to the early line. LIMITATIONS: Medication may have been dispensed but not actually taken. CONCLUSIONS: Higher costs during the first 45 days after evidence of the presence of TRD and during persistence on a late line relative to persistence on the early-line therapy suggest there are benefits to using more effective treatments earlier.

Prevalence of Pre-existing Conditions Relevant for Adverse Events and Potential Drug-Drug Interactions Associated with Augmentation Therapies Among Patients with Treatment-Resistant Depression.

INTRODUCTION: Pre-existing conditions relevant for adverse events (AE) and the potential for drug-drug interactions (DDIs) may limit safe pharmacotherapeutic augmentation options for patients with major depressive disorder (MDD). This concern may be heightened among patients with treatment-resistant depression (TRD), who often have comorbid medical disorders. METHODS: Adults with MDD and ≥ 1 antidepressant claim within the first observed major depressive episode were identified in the MarketScan® Databases. Those initiating a new regimen after two regimens at adequate dose and duration were considered to have TRD. The index date was defined at TRD onset or on a random antidepressant claim among patients with non-TRD MDD. Pre-existing conditions 12 months pre-index and potential DDIs 3 months pre/post-index associated with specific non-antidepressant augmentation therapies, including atypical antipsychotics (APs), buspirone, psychostimulants, anticonvulsants, thyroid hormone, and lithium were compared between 1:1 matched TRD and non-TRD MDD cohorts. RESULTS: Overall, 3414 patients with TRD and non-TRD MDD (mean age 39.7 years, 69% female) were matched. Relative to non-TRD MDD, patients with TRD had 33% higher likelihood of ≥ 1 pre-existing condition relevant for AEs listed in product labels of non-antidepressant augmentation therapies (p < 0.001). Patients with TRD vs. non-TRD MDD had 12.9 and 6.4 times higher likelihood of ≥ 2 and ≥ 3 DDIs, respectively, based on their medication regimen (all p < 0.001). CONCLUSION: Pre-existing conditions relevant for listed AEs and potential DDIs limit safe augmentation options in MDD, particularly among patients with TRD. Payer prior authorization policies requiring several augmentation therapy trials to access novel treatments may complicate clinical management of this population.

Prevalence, incidence and economic burden of schizophrenia among Medicaid beneficiaries.

OBJECTIVE: To estimate the prevalence, incidence and economic burden of schizophrenia among Medicaid beneficiaries. METHODS: Annual prevalence and incidence of schizophrenia among adult Medicaid beneficiaries were estimated during 2012-2017, by state and across six states (IA, KS, MS, MO, NJ and WI). The pooled estimate of the economic burden of schizophrenia was obtained during 1998Q1-2018Q1 across six states; adults with ≥2 diagnoses of schizophrenia were matched 1:1 to schizophrenia-free controls. The last observed schizophrenia diagnosis (schizophrenia cohort) or the last service claim (control cohort) with ≥12 months of continuous Medicaid enrollment before/after it defined the index date. Healthcare resource utilization (HRU) and costs ($2018 USD) incurred 12 months post-index were compared between cohorts. The economic burden of schizophrenia was also evaluated among young adults (18-34 years). RESULTS: Annual prevalence of schizophrenia ranged between 2.30% and 2.71% and annual incidence between 0.31% and 0.39% during 2012-2016. In 2017, only states with the highest incidence and prevalence rates (KS, MS, MO) had data, resulting in higher prevalence (4.01%) and incidence (0.52%). For the economic burden, adults with schizophrenia (N = 158,763) had higher HRU and incurred $14,087 higher healthcare costs versus controls (mean: $28,644 vs. $14,557), driven by $4677 higher long-term care costs (all p < .001). Young adults with schizophrenia incurred $14,945 higher healthcare costs versus controls, driven by $3473 higher inpatient costs (p < 0.001). CONCLUSIONS: Annual prevalence and incidence of schizophrenia varied by state but remained stable over time. Adults with schizophrenia incurred greater HRU and costs relative to adults without schizophrenia; the burden appeared comparable among young adults.

Economic burden in Medicaid beneficiaries with recently relapsed schizophrenia or with uncontrolled symptoms of schizophrenia not adherent to antipsychotics.

BACKGROUND: Patients with schizophrenia struggle with disease relapses and uncontrolled symptoms, which can either result in or be a result of non-adherence to antipsychotics (APs). The economic burden of such patients is hypothesized to be substantial. OBJECTIVE: To evaluate the economic burden of recently relapsed schizophrenia or of uncontrolled symptoms of schizophrenia with non-adherence to APs in Medicaid beneficiaries. METHODS: Adults with ≥ 2 schizophrenia diagnoses and controls without schizophrenia were identified in Medicaid data (1997Q1-2018Q1) from Iowa, Kansas, Mississippi, Missouri, New Jersey, and Wisconsin. The index date was the last observed schizophrenia diagnosis (cohort with schizophrenia) or the last service claim (control cohort) with ≥ 12 months of continuous Medicaid enrollment before and after it. Cohorts were matched 1:1 using propensity scores. After matching, two subgroups were identified among adults with schizophrenia: (1) patients with schizophrenia and a recent relapse (≥ 1 schizophrenia-related inpatient or emergency department claim ≤ 60 days before or on the index date) and (2) patients with uncontrolled symptoms of schizophrenia (≥ 2 schizophrenia-related hospitalizations) and non-adherence to APs (proportion of days covered < 80%) in the 12-month pre-index period. Previously matched controls were then subset to patients in each subgroup and their matched pairs without schizophrenia, thus maintaining the 1:1 matching ratio. Healthcare resource utilization (HRU) and costs ($2018 USD) in the 12-month post-index (observation) period were compared between matched pairs using adjusted regression models. RESULTS: Among 158,763 patients with schizophrenia, 18,771 (11.8%) had a recent relapse (mean age 50.5 years; 48.6% female, 51.4% male) and 13,697 (8.6%) were not adherent to APs and had uncontrolled symptoms of schizophrenia (mean age 47.1 years; 48.0% female, 52.0% male). During the observation period, patients with recently relapsed schizophrenia and those non-adherent to APs with uncontrolled symptoms of schizophrenia had significantly higher HRU relative to their controls without schizophrenia. Patients with recently relapsed schizophrenia had mean total healthcare costs $21,862 higher relative to their controls ($37,424 vs $15,563), driven by $8,486 higher mean long-term care costs (all P < 0.001). Patients non-adherent to APs with uncontrolled symptoms of schizophrenia had adjusted mean total healthcare costs $20,787 higher relative to their controls ($38,337 vs $15,241), driven by $8,019 higher adjusted mean inpatient costs (all P < 0.001). Additional total healthcare costs incurred by patients with recently relapsed schizophrenia and those of patients non-adherent to APs with uncontrolled symptoms of schizophrenia exceeded by 55.2% and 47.6%, respectively, incremental total healthcare costs incurred by all patients with schizophrenia ($14,087). CONCLUSIONS: Patients with recently relapsed schizophrenia and those non-adherent to AP therapy with uncontrolled symptoms of schizophrenia incurred higher HRU and costs relative to patients without schizophrenia. Additional healthcare costs of these subgroups of patients with schizophrenia appeared higher than in the overall population with schizophrenia. DISCLOSURES: This study was supported by Janssen Scientific Affairs, LLC. The sponsor was involved in the study design, data collection, data analysis, manuscript preparation, and publication decisions. Pilon, Lafeuille, Zhdanava, Côté-Sergent, Rossi, and Lefebvre are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Janssen Scientific Affairs, LLC, which funded the development and conduct of this study and manuscript. Patel, Joshi, and Lin are employees of Janssen Scientific Affairs, LLC and stockholders of Johnson & Johnson. Part of the material in this manuscript has been presented at the US Psych Congress, October 3-6, 2019, San Diego, CA, and at the Virtual ISPOR Meeting, May 18-20, 2020.

The Prevalence and National Burden of Treatment-Resistant Depression and Major Depressive Disorder in the United States.

OBJECTIVE: Estimates of prevalence and burden of treatment-resistant depression (TRD) vary widely in the literature. This study evaluated the prevalence and burden of TRD and the share of TRD in the burden of medication-treated major depressive disorder (MDD) using the most commonly accepted definition of TRD and a novel bottom-up approach. METHODS: Prevalence and health care burden of TRD were estimated by synthetizing inputs across 4 similarly designed claims studies in adults covered by Medicare, Medicaid, commercial plans, and the US Veterans Health Administration (VHA). Productivity (absenteeism and presenteeism) and unemployment burden were estimated based on inputs from a study conducted with data from the Kantar National Health and Wellness Survey (NHWS; 2017). A targeted literature search for additional inputs was performed. A cost model was developed to estimate the burden of TRD and medication-treated DSM-5-defined MDD in the United States. Study outcomes were the 12-month prevalence of TRD and the annual health care, productivity, and unemployment burden of TRD and medication-treated MDD in the United States. RESULTS: The estimated 12-month prevalence of medication-treated MDD in the United States was 8.9 million adults, and 2.8 million (30.9%) had TRD. The total annual burden of medication-treated MDD among the US population was $92.7 billion, with $43.8 billion (47.2%) attributable to TRD. The share of TRD was 56.6% ($25.8 billion) of the health care burden, 47.7% ($8.7 billion) of the unemployment burden, and 32.2% ($9.3 billion) of the productivity burden of medication-treated MDD. CONCLUSIONS: TRD is associated with disproportionate health care costs and unemployment, suggesting potentially large economic and societal gains with effective management.

Antipsychotic Adherence, Resource Use, and Costs Before and After the Initiation of Once-monthly Paliperidone Palmitate Therapy Among Medicaid Beneficiaries With Prior Schizophrenia Relapse.

PURPOSE: Patients with schizophrenia often struggle with medication adherence and may benefit from the use of a long-acting injectable antipsychotic, including once-monthly paliperidone palmitate (PP1M), which was previously demonstrated to improve outcomes compared with oral antipsychotics. This study assessed the impact of initiating PP1M therapy on medication adherence, health care resource use (HRU), and costs among Medicaid beneficiaries with schizophrenia and a prior schizophrenia relapse. METHODS: A 6-state Medicaid database (from quarter 1 of 2009 to quarter 1 of 2018) was used to identify adults with ≥2 schizophrenia diagnoses who started PP1M therapy on or after January 1, 2010. The index date was the first PP1M claim. Patients had ≥12 months of continuous Medicaid enrollment before and after the index date, ≥1 oral antipsychotic claim in the 12 months before the index date, and ≥1 relapse (proxied as a schizophrenia-related inpatient admission or emergency department [ED] visit) during the 12 months before the index date. Generalized estimating equations were used to compare adherence to antipsychotics (proportion of days covered ≥80%), HRU, and costs (reported in 2018 US dollars) in the 12 months after versus before the index date. Sensitivity analyses were conducted (1) accounting for the minimum and cumulative price inflation Medicaid rebates for pharmacy costs of branded psychiatric medications, (2) among patients with ≥2, ≥3, and ≥4 prior schizophrenia-related inpatient admissions or ED visits, (3) among patients not adherent to antipsychotic treatment before the index date, and (4) among patients switching to PP1M directly from oral risperidone or paliperidone. FINDINGS: A total of 1725 patients met the study inclusion criteria (mean age, 39.5 years; 43% female). After versus before the index date, patients were 93% more likely to be adherent to antipsychotic treatment (P < 0.01). The likelihood of inpatient admissions and ED visits decreased by 89% and 49% (all P < 0.01) after initiating PP1M therapy. The number of inpatient days decreased by 31% (P < 0.01) and the number of ED visits by 16% (P = 0.03). Pharmacy costs increased by $514 per-patient-per-month (PPPM), whereas medical costs, driven by inpatient costs, decreased by $391 PPPM (all P < 0.01). Sensitivity analyses yielded similar trends. Notably, total health care cost savings of $231 PPPM were observed after accounting for the cumulative Medicaid rebate for costs of branded psychiatric medications (P < 0.01). IMPLICATIONS: In Medicaid beneficiaries with relapsed schizophrenia, transitioning from oral antipsychotics to PP1M was associated with improved adherence to antipsychotics and decreased use of inpatient and ED services. Increased pharmacy costs after the initiation of PP1M were offset by decreased medical costs. After applying the cumulative Medicaid rebate, including the price inflation rebate for costs of branded psychiatric medications, initiation of PP1M therapy resulted in statistically significant health care cost savings.

Medication adherence, healthcare resource utilization, and costs among Medicaid beneficiaries with schizophrenia treated with once-monthly paliperidone palmitate or once-every-three-months paliperidone palmitate.

OBJECTIVE: Antipsychotics with reduced dosing frequency may improve adherence and clinical outcomes for patients with schizophrenia. This study compared treatment patterns, healthcare resource utilization (HRU), and costs between Medicaid beneficiaries with schizophrenia treated with once-monthly paliperidone palmitate (PP1M) and those who transitioned to once-every-three-months paliperidone palmitate (PP3M). METHODS: Adults with schizophrenia were identified in a four-state Medicaid database (18 May 2014 to 31 March 2019). The index date was the first PP3M claim (PP3M cohort), or a random PP1M claim (PP1M cohort), following ≥4 months of continuous PP1M treatment among patients with ≥12 months of continuous Medicaid enrollment pre- and post-index. Adherence (proportion of days covered by the index treatment ≥80%), persistence (no gap >90/30 days in the PP3M/PP1M supply), HRU, and costs were compared during the 12-month post-index period between cohorts matched 1:1. RESULTS: Among 2374 patients identified, 374 remained in each cohort after matching (mean age 42 years; 30.5% female). Compared to the PP1M cohort, the PP3M cohort was 2.39 times more likely to be adherent (p < .001), 4.63 times more likely to be persistent (p < .001), 33% less likely to have ≥1 hospitalization (p = .011), and 32% less likely to have ≥1 day with home care services (p = .012). Mean annual medical costs were similar between cohorts ($24,970 in the PP3M cohort and $25,736 in the PP1M cohort; p = .854). CONCLUSIONS: Medicaid beneficiaries who transitioned to PP3M had higher adherence and persistence, and a reduced likelihood of hospitalization relative to those who continued treatment with PP1M. The results suggest potential clinical value to transitioning eligible patients to PP3M.

Economic burden of treatment-resistant depression in privately insured US patients with co-occurring anxiety disorder and/or substance use disorder.

OBJECTIVE: To assess the burden of treatment-resistant depression (TRD) among privately insured patients with anxiety disorder and/or substance use disorders (SUD). METHODS: Adults <65 years old were identified in the Optum Health Care Solutions Inc. database (July 2009-March 2017). Among those with major depressive disorder (MDD) and antidepressant use, patients who initiated a third antidepressant (index date) after two regimens at adequate dose and duration were classified in the TRD cohort and patients without evidence of TRD were classified in the non-TRD MDD control cohort. The non-MDD control cohort comprised patients without MDD. In the non-TRD MDD and non-MDD cohorts, the index date was imputed to mimic the distribution of time in the TRD cohort from the first antidepressant to the index date or from the start of eligibility to the index date, respectively. Patients with <6 months of continuous insurance eligibility pre-/post-index, psychosis, schizophrenia, bipolar disorder and related conditions, dementia, and development disorders, and/or no baseline anxiety disorder and/or SUD were excluded. Patients with TRD were matched 1:1 to patients with non-TRD MDD and patients without MDD, based on exact matching factors (i.e. availability of work loss data) and propensity scores computed based on characteristics measured pre-index. Outcomes, including healthcare resource use (HRU) and costs, work productivity loss and related costs measured per patient per year ≤24 months post-index were compared between matched TRD, non-TRD MDD and non-MDD cohorts. RESULTS: A total of 3166 patients were identified in the TRD cohort and matched to non-TRD MDD and non-MDD cohorts. Among patients with TRD (mean age 39 years, 60.5% female), 87.3% had an anxiety disorder, 24.1% had SUD. The TRD cohort had higher HRU vs non-TRD MDD and non-MDD cohorts: 0.32 vs 0.20 and 0.14 inpatient admissions, 0.91 vs 0.73 and 0.58 emergency department visits, and 23.8 vs 16.8 and 11.6 outpatient visits, respectively (all p < .01). The TRD cohort had higher healthcare costs ($16,674) vs non-TRD MDD ($10,945) and non-MDD ($6493) cohorts (all p < .01). Among patients with work loss data (N = 310/cohort), patients with TRD had more work loss days (54) and higher work loss-related costs ($13,674) vs patients with non-TRD MDD (32 days; $7131) and without MDD (17 days; $4798; all p < .01). CONCLUSIONS: In patients with an anxiety disorder and/or SUD, TRD was associated with higher HRU, healthcare costs, work loss days and work loss-related costs.

Economic Burden of Treatment-Resistant Depression in Privately Insured U.S. Patients with Physical Conditions.

BACKGROUND: Little is known about the economic burden of treatment-resistant depression (TRD) in patients with physical conditions. OBJECTIVE: To assess health care resource utilization (HRU) and costs, work loss days, and related costs in patients with TRD and physical conditions versus patients with the same conditions and non-TRD major depressive disorder (MDD) or without MDD. METHODS: Adults aged < 65 years with MDD treated with antidepressants were identified in the OptumHealth Care Solutions database (July 2009-March 2017). Patients who received a diagnosis of MDD and initiated a third antidepressant regimen (index date) after 2 regimens of adequate dose and duration were defined as having TRD. Patients with non-TRD MDD and without MDD were assigned a random index date. Patients with < 6 months of continuous health plan eligibility pre- or post-index; a diagnosis of psychosis, schizophrenia, bipolar disorder/mania, dementia, and developmental disorders; and/or no baseline physical conditions (cardiovascular, metabolic, and respiratory disease or cancer) were excluded. Patients with TRD were matched 1:1 to each of the non-TRD MDD and non-MDD cohorts based on propensity scores. Per patient per year HRU, costs, and work loss outcomes were compared up to 24 months post-index date using negative binominal and ordinary least square regressions. RESULTS: A total of 2,317 patients with TRD (mean age, 47.6 years; 63.1%, female; mean follow-up, 19.7 months) had ≥ 1 co-occurring key physical condition (cardiovascular, 52.5%; metabolic, 48.2%; respiratory, 16.4%; and cancer, 9.5%). Relative to non-TRD MDD and non-MDD cohorts, respectively, patients with TRD had 46% and 235% more inpatient admissions, 28% and 128% more emergency department visits, and 53% and 155% more outpatient visits (all P < 0.05). Health care costs were $22,541 in the TRD cohort, $17,450 in the non-TRD MDD cohort, and $10,047 in the non-MDD cohort, yielding cost differences of $5,091 (vs. non-TRD MDD) and $12,494 (vs. non-MDD; all P < 0.01). In patients with work loss data available (n = 278/cohort), those with TRD had 2.0 and 2.9 times more work loss as well as $8,676 and $10,323 higher work loss costs relative to those with non-TRD MDD and without MDD, respectively (all P < 0.001). CONCLUSIONS: In patients with physical conditions, those with TRD had higher HRU and health care costs, work loss days, and associated costs compared with non-TRD MDD and non-MDD cohorts. DISCLOSURES: This study was sponsored by Janssen Scientific Affairs (JSA), which was involved in all aspects of the research, including the design of the study; the collection, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication. Joshi and Daly are employed by JSA. Zhdanava, Pilon, Rossi, Morrison, and Lefebvre are employees of Analysis Group, which received funding from JSA for conducting this study and has received consulting fees from Novartis Pharmaceuticals and GSK, unrelated to this study. Kuvadia is employed by Integrated Resources, which has provided research services to JSA unrelated to this study; Joshi reports past employment by and stock ownership in Johnson & Johnson; Nelson reports advisory board, data and safety monitoring board, and consulting fees from Assurex, Eisai, FSV-7, JSA, Lundbeck, Otsuka, and Sunovion and royalties from UpToDate, unrelated to this study. This work was presented at AMCP Nexus 2019, held in National Harbor, MD, from October 29 to November 1, 2019.

Are Medicaid Coverage Gaps Associated with Higher Health Care Resource Utilization and Costs in Patients with Schizophrenia?

The objective was to assess the association of Medicaid coverage gaps with health care resource utilization (HRU) and costs of patients with schizophrenia. Patients with schizophrenia were identified from the Medicaid database. The beginning of the first eligible gap was defined as the index date. Per-patient per-month (PPPM) HRU and costs before versus after a gap were assessed, and the association between gap duration and PPPM HRU and costs was examined up to 12 months post index. Together with 95% confidence intervals, HRU differences were reported in rate ratios (RRs), and cost differences were reported in 2016 US dollars. A subgroup of males with substance use disorder (SUD; risk factors for incarceration) also was analyzed. Total PPPM health care costs increased significantly by $711.04 following a coverage gap (P < 0.001). Gaps of 180-365 days were associated with a significant increase in inpatient visits (RR = 1.27; P < 0.001) relative to gaps of <90 days. Gaps of 90-179 days were associated with significantly more PPPM inpatient visits (RR = 1.14; P = 0.024) relative to a gap of <90 days. Inpatient costs were particularly increased for gaps of 180-365 days versus those of <90 days (cost difference = $101.81 PPPM; P = 0.0008). Similar results were found in male patients with SUD, in whom HRU and cost differences appeared larger. In patients with schizophrenia, longer Medicaid coverage gaps were associated with increases in inpatient admissions, emergency room visits, and inpatient costs, particularly among patients with risk factors for incarceration. These results support policies that aim to facilitate Medicaid reinstatement for patients with schizophrenia.