Healthcare resource utilization and costs before and after long-acting injectable antipsychotic initiation in commercially insured young adults with schizophrenia.

BACKGROUND: Long-acting injectable (LAI) antipsychotics use is associated with improved adherence which can reduce the rate of relapse, hospitalization, and associated costs in patients with schizophrenia. Young adults could be at higher risk of poor adherence, hence use of LAI in this population may offer a benefit but the evidence is limited. This study aimed to compare clinical and economic outcomes before and after the initiation of LAI antipsychotics in commercially insured young adults (18-35 years of age) with schizophrenia. METHODS: A retrospective claims data study was conducted using the data from the IBM MarketScan® Commercial Claims and Encounters (CCAE) Database. Patients with a continuous enrollment of at least 1-year before and 1-year after the first observed schizophrenia diagnosis (index date) and with the use of ≥1 typical or atypical LAI antipsychotic during the post-index follow-up period were included. A pre-post analysis was conducted to compare relapse rates, healthcare resource utilization, and costs before (from index date to LAI initiation) and after LAI initiation (to end of follow up). RESULTS: A total of 2222 patients who initiated LAIs after an index schizophrenia diagnosis were identified. The per patient per month (PPPM) composite relapse event rate (0.109 pre-LAI to 0.073 post-LAI) and hospitalization rate (0.091 to 0.058), all-cause inpatient visits (0.231 to 0.119), and length of stay (2.694 to 1.092 days) significantly decreased from before LAI initiation to after LAI initiation with similar trends seen for mental health and schizophrenia-related measures (all significant; P < 0.0001). All-cause total costs ($4898 to $3078 PPPM) were also decreased after LAI initiation, with similar trends seen for mental health and schizophrenia-related costs (all significant; P < 0.0001). Although medication costs were higher post-LAI period ($311 to $542 PPPM), the cost increase was substantially offset by the decreased costs associated with total healthcare costs. CONCLUSIONS: Treatment with LAI antipsychotics was associated with a decrease in relapse event rate, healthcare resource utilization, and costs after LAI initiation compared to before LAI initiation in commercially insured young adults with schizophrenia. Treatment with LAIs in young adults with schizophrenia is potentially associated with significant cost savings to commercial payers.

Patient-psychiatrist discordance and drivers of prescribing long-acting injectable antipsychotics for schizophrenia management in the real-world: a point-in-time survey.

BACKGROUND: To assess discordance between psychiatrists and their patients with schizophrenia regarding disease management and understand drivers of prescribing long-acting injectable (LAI) antipsychotics. METHODS: Data were collected via the Adelphi Schizophrenia Disease Specific Programme™, a point-in-time real-world international survey of psychiatrists and their consulting patients with schizophrenia, conducted in 2019. Psychiatrists completed an attitudinal survey on schizophrenia management and provided patient profiles for their next 10 adult consulting patients. The same patients voluntarily completed patient self-completion forms. Disease severity and improvement were assessed via physician-reported Clinical Global Impression scale; patients' adherence to treatment was rated through a 3-point scale (1=not at all adherent, 3=fully adherent). RESULTS: Four hundred sixty-six psychiatrists provided data for 4345 patients (1132 receiving a LAI; 3105 on non-LAI treatment; 108 not on treatment). LAIs were more commonly prescribed to patients with severe schizophrenia, with varying reasons for prescribing. Globally, only slight agreement was observed between psychiatrists and patients for Clinical Global Impression severity of illness (κ=0.174) and level of improvement on treatment (κ=0.204). There was moderate agreement regarding level of adherence to treatment (κ=0.524). Reasons for non-adherence did not reach a level of agreement greater than fair. CONCLUSIONS: Our real-world survey found that LAIs were more often reserved for severe schizophrenia patients and improving adherence was a key driver for prescribing. However, compared with the patients themselves, psychiatrists tended to underestimate patients' disease severity and overestimate their adherence.

Unemployment, homelessness, and other societal outcomes in patients with schizophrenia: a real-world retrospective cohort study of the United States Veterans Health Administration database : Societal burden of schizophrenia among US veterans.

BACKGROUND: The burden associated with schizophrenia is substantial. Impacts on the individual, healthcare system, and society may be particularly striking within the veteran population due to the presence of physical and mental health comorbidities. Disease burden is also influenced by a complex interplay between social determinants of health and health disparities. The objective of the current study was to compare non-healthcare societal outcomes between veterans with and without schizophrenia in the United States Veterans Health Administration (VHA). METHODS: A retrospective cohort study was conducted using the VHA database (01/2013-09/2019; study period). Veterans with schizophrenia (≥2 diagnoses of ICD-9295.xx, ICD-10 F20.x, F21, and/or F25.x during the study period) were identified; the index date was the earliest observed schizophrenia diagnosis. Veterans with schizophrenia were propensity score-matched to those without schizophrenia using baseline characteristics. A 12-month baseline and variable follow-up period were applied. The frequency of unemployment, divorce, incarceration, premature death, and homelessness were compared between the matched cohorts using standardized mean difference (SMD). Risk of unemployment and homelessness were estimated using logistic regression models. RESULTS: A total of 102,207 veterans remained in each cohort after matching (91% male; 61% White [per AMA]; median age, 59 years). Among veterans with schizophrenia, 42% had a substance use disorder and 30% had mental health-related comorbidities, compared with 25 and 15%, respectively, of veterans without schizophrenia. Veterans with schizophrenia were more likely to experience unemployment (69% vs. 41%; SMD: 0.81), divorce (35% vs. 28%; SMD: 0.67), homelessness (28% vs. 7%; SMD: 0.57), incarceration (0.4% vs. 0.1%; SMD: 0.47), and premature death (14% vs. 12%; SMD < 0.1) than veterans without schizophrenia. After further adjustments, the risk of unemployment and of homelessness were 5.4 and 4.5 times higher among veterans with versus without schizophrenia. Other predictors of unemployment included Black [per AMA] race and history of substance use disorder; for homelessness, younger age (18-34 years) and history of mental health-related comorbidities were additional predictors. CONCLUSION: A greater likelihood of adverse societal outcomes was observed among veterans with versus without schizophrenia. Given their elevated risk for unemployment and homelessness, veterans with schizophrenia should be a focus of targeted, multifactorial interventions to reduce disease burden.

Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in a Rapid-Initiation Model of Care for Human Immunodeficiency Virus Type 1 Infection: Primary Analysis of the DIAMOND Study.

BACKGROUND: Most guidelines recommend rapid treatment initiation for patients with newly diagnosed human immunodeficiency virus type 1 (HIV-1) infection, but prospective US data are limited. The DIAMOND (NCT03227861) study using darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is a phase 3 prospective study evaluating efficacy/safety of a single-tablet regimen in a rapid-initiation model of care. METHODS: Adults aged ≥18 years began D/C/F/TAF ≤14 days from diagnosis without screening/baseline results; as results became available, participants not meeting predefined safety/resistance stopping rules continued. Primary endpoint was virologic response (HIV-1 RNA <50 copies/mL; intent-to-treat; US Food and Drug Administration [FDA] snapshot) at week 48; participant satisfaction was measured via the HIV Treatment Satisfaction Questionnaire status version (HIVTSQs). RESULTS: Of 109 participants, 87% were male, 32% black/African American, median (range) age was 28 (range, 19-66) years, 25% of participants had HIV-1 RNA ≥100 000 copies/mL, 21% had CD4+ cell count <200 cells/µL, and 31% enrolled ≤48 hours from diagnosis. At week 48, 97 (89%) participants completed the study and 92 (84%) achieved HIV-1 RNA <50 copies/mL (FDA snapshot). There were no protocol-defined virologic failures; incidences of adverse events (AEs) and adverse drug reactions (33%) were low, no serious AEs were study drug related, and 1 (<1%) participant discontinued due to study drug related AE(s). The overall HIVTSQs score at week 48 was 58 (maximum: 60). CONCLUSIONS: At week 48, a high proportion of participants starting D/C/F/TAF achieved HIV-1 RNA <50 copies/mL and very few discontinued therapy. D/C/F/TAF was well tolerated, no participants discontinued due to baseline resistance stopping criteria, and high treatment satisfaction among participants was recorded. CLINICAL TRIALS REGISTRATION: NCT03227861.

An Evaluation of the Clinical and Economic Burden Among Older Adult Medicare-Covered Beneficiaries With Treatment-Resistant Depression.

OBJECTIVE: To compare the clinical and economic burden of treatment-resistant depression (TRD) among older adult patients with major depressive disorder (MDD) to non-TRD MDD and non-MDD patients. METHODS: Retrospective cohort study using 5% Medicare data (January 1, 2012-December 31, 2015) for MDD patients aged ≥65 years who were defined as TRD if they received ≥2 antidepressant treatments in the current episode. MDD patients not meeting TRD criteria were deemed non-TRD MDD; those without an MDD diagnosis were categorized as non-MDD. All were required to have continuous health plan enrollment for ≥6 months pre- and ≥12 months postindex date (index: first antidepressant claim/random [non-MDD]). Three cohorts were matched, and generalized linear and Cox proportional hazards models were used to compare medication use, healthcare resource utilization, costs, and risks of initial hospitalization and readmission ≤30 days postdischarge from initial hospitalization. RESULTS: After matching, 178 patients from each cohort were analyzed. During 12 months of follow-up, TRD patients had higher use of different antidepressants and antipsychotics, higher inpatient and emergency room visits, longer inpatient stays, and higher total healthcare costs ($24,543 versus $16,059, $8,058) than non-TRD MDD and non-MDD cohorts, respectively (all p <0.05). Risk of initial hospitalization was higher in the TRD (hazard ratio [HR] = 3.60, 95% confidence interval [CI] = 2.08-6.23) and non-TRD MDD cohorts (HR = 1.82, 95% CI = 1.02-3.25) than the non-MDD cohort. CONCLUSIONS: The burden of MDD among older adult Medicare beneficiaries is substantial, and even greater among those with TRD compared to non-TRD MDD, demonstrating the need for more effective treatments than those currently available.

Humanistic outcomes in treatment resistant depression: a secondary analysis of the STAR*D study.

BACKGROUND: In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, a third of patients did not achieve remission or adequate response after two treatment trials, fulfilling requirements for treatment resistant depression (TRD). The present study is a secondary analysis of the STAR*D data conducted to compare the humanistic outcomes in patients with TRD and non-TRD MDD. METHODS: Patients with major depressive disorder who entered level 3 of the STAR*D were included in the TRD group, while patients who responded to treatment and entered follow-up from level 1 or 2 were included in the non-TRD group. The first visit in level 1 was used for baseline assessments. The time-point of assessments for comparison was the first visit in level 3 for TRD patients (median day: 141), and the visit closest to 141 ± 60 days from baseline for non-TRD patients. Outcomes were assessed by the 12-item Short Form Health Survey (SF12), 16-item Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Work and Social Adjustment Scale (WSAS), and Work Productivity and Activity Impairment scale (WPAI). Scores were compared in a linear model with adjustment for covariates including age, gender, and depression severity measured by the 17-item Hamilton Rating Scale for Depression (HDRS17) and Quick Inventory of Depressive Symptomatology (QIDS). RESULTS: A total of 2467 (TRD: 377; non-TRD: 2090) patients were studied. TRD patients were slightly older (mean age 44 vs 42 years), had a higher proportion of men (49% vs 37%, p < .0001), and baseline depression severity (HDRS17: 24.4 vs 22.0, p < .0001) vs non-TRD patients. During follow-up, TRD patients had lower health-related quality of life (HRQOL) scores on mental (30 vs 45.7) and physical components (47.7 vs 48.9) of the SF12, and lower Q-LES-Q scores (43.6 vs 63.7), greater functional and work impairments and productivity loss vs non-TRD patients (all p < 0.05). CONCLUSION: Patients with TRD had worse HRQOL, work productivity, and social functioning than the non-TRD patients.

Meta-Analysis of Caregiver-Directed Psychosocial Interventions for Schizophrenia.

With the recent movement toward a personal-recovery paradigm to treat schizophrenia, the locus of mental health care delivery has shifted toward community-based care. Family caregivers comprise a substantial component of that community, and are often providing care for longer periods, but often have no formal training or support. Caregiver-directed psychosocial interventions (CDPI) have been developed to train and assist caregivers in their efforts to maximize the odds of treatment success for those in their care. This meta-analysis compared CDPI versus treatment as usual (TAU) on outcomes such as hospitalization, relapse, non-compliance, and "other outcomes" (emergency services utilization, suicide attempt, and death). A systematic literature search (2005-2015) was conducted to identify randomized controlled trials of outpatient administered CDPI versus TAU to treat adult patients recovering from schizophrenia. Relative risks (RR) with 95% confidence intervals derived via random effects meta-analysis were calculated to compare CDPI versus TAU on the aforementioned outcomes. Eighteen of the 693 citations were retained for analysis. Overall RR for CDPI versus TAU suggested improved outcomes associated with CDPI: hospitalization [0.62 (0.46, 0.84) p < 0.00001], relapse [0.58 (0.47, 0.73) p < 0.00001] and other outcomes [0.70 (0.19, 2.57) p = 0.59]. CDPI was associated with significantly better compliance with medication and clinical activities combined [0.38 (0.19, 0.74) p = 0.005]. Medication compliance alone favored CDPI but was non-significant. Compliance with clinical activities alone favored CDPI significantly [0.22 (0.11, 0.47) p < 0.00001]. CDPI is associated with reductions in hospitalization, relapse, and treatment non-compliance.

Comparison and predictors of treatment adherence and remission among patients with schizophrenia treated with paliperidone palmitate or atypical oral antipsychotics in community behavioral health organizations.

BACKGROUND: Nonadherence to antipsychotic treatment increases the likelihood of relapse and progressive symptomatology in patients with schizophrenia. Atypical long-acting injectables, including paliperidone palmitate (PP), may increase adherence and improve symptoms. This study compared and assessed predictors of treatment patterns and symptom remission among schizophrenia patients treated with PP versus atypical oral antipsychotic therapy (OAT) in community behavioral health organizations (CBHOs). METHODS: This retrospective cohort analysis evaluated 763 patients with schizophrenia and new (PP-N; N = 174) or continuing (PP-C; N = 308) users of PP, or new users of OAT (N = 281) at enrollment in the REACH-OUT study (2010-2013). Treatment outcomes assessed at 1 year were discontinuation, and adherence, measured by proportion of days covered (PDC) or medication possession ratio (MPR). Remission status was assessed using the Structured Clinical Interview for Symptoms of Remission (SCI-SR). A machine learning platform, Reverse Engineering and Forward Simulation (REFS™), was used to identify predictors of study outcomes. Multivariate Cox and generalized linear regressions estimated the adjusted hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals. RESULTS: Among PP-N users, 27% discontinued their initial treatment regimen versus 51% (p < 0.001) of OAT users. PP-N (vs OAT; HR = 0.49 [0.31-0.76]) users and males (HR = 0.65 [0.46-0.92]) had significantly lower rates of discontinuation. Relative to OAT, PP-N had a 36% [31%-42%] higher MPR and a 10-fold increased achievement of PDC ≥80% (OR = 10.46 [5.72-19.76]). PP users were significantly more likely to achieve remission in follow-up (PP-N vs OAT: OR = 2.65 [1.39-5.05]; PP-C vs OAT: OR = 1.83 [1.03-3.25]). CONCLUSIONS: Relative to OAT, PP was associated with improved adherence, less frequent treatment discontinuation, and improved symptom remission in this CBHO study population.

Impact of noncancer pain on health-related quality of life.

BACKGROUND: While the economic costs of pain have been documented, the impact of noncancer pain on quality of life has not been studied extensively. OBJECTIVE: To estimate the influence of noncancer pain on quality of life measures. DESIGN: Prospective, multicenter, observational nonrandomized patient pain registry. SETTING: Outpatient settings. PARTICIPANTS: Patients with acute episodes of noncancer pain requiring treatment with a prescription medication containing oxycodone immediate-release on an as-needed basis for at least 5 days (n = 629). MEASUREMENTS: The modified Brief Pain Inventory and the 12-item Short Form Health Survey (SF-12) was measured at baseline when oxycodone immediate-release began and days 7, 14, 21, and 28. Repeated measures mixed models provided estimates of impact of pain on the physical component summary score (PCS) and mental health component summary score (MCS) of the SF-12. RESULTS: Patterns indicating pain oscillation over the 28-day window were common (Range: 44.3% back/neck pain cohort to 61.2% postoperative cohort). After adjustment for sociodemographics, concomitant medications and gastrointestinal symptoms, worst pain in 24 hours was associated with a 13.9 point PCS reduction (adjusted PCS for pain = 10: 31.1; adjusted PCS for pain = 0: 45.0) and a 7.2 point MCS reduction (adjusted MCS for pain = 10: 44.1; adjusted MCS for pain = 0: 51.3). Similar clinically relevant differences were observed among patients with arthritis, back/neck pain, injury/trauma, postoperative pain, neuropathic pain and fibromyalgia, although statistical significance was not observed in the latter 2 groups. CONCLUSION: Among outpatients with various underlying causes of pain, the negative impact of pain on physical and mental health-related quality of life is significant.

Post Hospitalization Clinical Quality Outcomes Among US Patients with Schizophrenia Treated with a Long-Acting Injectable or Switched to a New Oral Antipsychotic: A Retrospective Cohort Study.

BACKGROUND:  Adherence to antipsychotic medication and care discontinuity remain a challenge to healthcare practitioners providing care to patients with schizophrenia. OBJECTIVE: This study used real-world data from a US hospital-based, all-payer database to examine clinical quality measures among patients with schizophrenia initiated on a long-acting injectable (LAI) or switched to a new oral antipsychotic medication (OAP) following a hospitalization. METHODS: A retrospective cohort study using the PINC AI™ Healthcare Database compared two cohorts of patients with schizophrenia on post-index hospitalization clinical quality and care continuity endpoints. Patients initiated on an LAI (n = 7292) or switched to a new OAP (n = 31,956) during an index hospitalization between April 2017 and April 2020 were included. Propensity score weighting addressed differences in patient, hospital, and clinical characteristics between the two cohorts. RESULTS: Patients who initiated an LAI experienced significantly greater adjusted 30-day antipsychotic medication continuation to index therapy, higher rate of 30-day outpatient follow-up care, longer mean time to discontinuation of index therapy, and lower risk of discontinuing their index treatment compared to patients who switched to a new OAP (all p values < 0.001). Probability of 30-day antipsychotic medication continuation was significantly higher for LAI initiators than for patients who switched to a new OAP, even after controlling for patient, clinical, and hospital characteristics (adjusted odds ratio = 1.2, 95% CI 1.1-1.3, p < 0.001). CONCLUSION: Patients who initiated an LAI in a hospital setting experienced better clinical quality and care continuity outcomes compared to patients who were switched to a new OAP. These findings may be useful in identifying solutions to help improve the quality of medication management post-hospital discharge among patients with schizophrenia.

Out-of-Pocket Costs for Long-Acting Injectable and Oral Antipsychotics Among Medicare Patients With Schizophrenia.

OBJECTIVE: The authors sought to describe out-of-pocket (OOP) costs among beneficiaries with schizophrenia differing in Medicare Part D low-income subsidy (LIS) status. METHODS: National 100% Medicare claims were used to identify all adult fee-for-service Medicare Part D beneficiaries with schizophrenia who used antipsychotics in 2019 (N=283,813). Proportions of patients by LIS status, OOP costs per prescription, and annual OOP costs were reported. Results were stratified by type of antipsychotic received (oral antipsychotic [OAP], first-generation long-acting injectable [FGA-LAI], or second-generation long-acting injectable [SGA-LAI]). RESULTS: In the final sample, 90.3% of beneficiaries had full LIS status, paying minimal copayments (29.6% institutionalized full LIS, paying $0; 42.2% noninstitutionalized full LIS, ≤100% federal poverty level [FPL], paying $1.25-$3.80; and 18.5% noninstitutionalized full LIS, >100% FPL, paying $3.40-$8.50). Only 0.9% of the sample received partial LIS status, and 8.8% had a non-LIS status. Non-LIS beneficiaries had the highest OOP costs, followed by partial LIS beneficiaries. Before entering catastrophic coverage, median OOP costs per prescription for generic OAPs, brand-name OAPs, FGA-LAIs, and SGA-LAIs were $10.85, $171.97, $26.09, and $394.28, respectively, for non-LIS beneficiaries and $3.69, $105.82, $9.35, and $229.20, respectively, for partial LIS beneficiaries. The annual total OOP costs varied substantially by LIS status (full LIS, $0-$130.79; partial LIS, $458.96; non-LIS, $998.81). CONCLUSIONS: Most Medicare beneficiaries with schizophrenia qualified for full LIS and faced minimal OOP costs for both OAPs and LAIs. The remainder (i.e., partial LIS and non-LIS beneficiaries) faced substantial OOP costs, both per prescription and annually, especially for SGA-LAIs.

Treatment patterns and hospitalizations following rejection, reversal, or payment of the initial once-monthly paliperidone palmitate long-acting injectable antipsychotic claim among patients with schizophrenia or schizoaffective disorder.

BACKGROUND: Once-monthly paliperidone palmitate (PP1M) is a long-acting injectable antipsychotic approved for the treatment of schizophrenia and schizoaffective disorder (SCA) in adults. OBJECTIVE: To assess treatment patterns and schizophrenia/SCA-related hospitalization following payer rejection, patient reversal, or payment of an initial PP1M claim. METHODS: This was a retrospective cohort study using the IQVIA Formulary Impact Analyzer database linked to the Medical Claims, Hospital Charge Detail Master, and Experian consumer databases. Patients with schizophrenia/SCA and ≥1 PP1M pharmacy claim from January 1, 2018, to February 28, 2022, were identified and stratified into 3 cohorts based on the transaction status of the initial PP1M claim (index date): rejected (payer not approved), reversed (payer approved, patient abandoned), and paid (payer approved, patient filled). Patient characteristics during the 12 months before the index date, subsequent treatment patterns, and schizophrenia/SCA-related hospitalization for patients with >6 months of follow-up were assessed by cohort. RESULTS: The rejected, reversed, and paid cohorts included 1,260, 1,046, and 1,686 patients, respectively. Across these cohorts, the mean ages ranged between 39.2 and 44.5 years; more than half were male (50.8%-51.6%) and White (50.6%-58.3%); 19.8%-24.6% of patients had a Quan-Charlson Comorbidity Index score of ≥2. Rates of prior atypical oral and long-acting injectable antipsychotic use ranged between 76.4%-80.3% and 7.8%-12.7%, respectively. Among patients with ≥6 months of follow-up, 52.2% in the rejected and 53.1% in the reversed cohorts had a subsequent paid PP1M claim during the study period; the median (quartile 1-quartile 3) time to the first paid PP1M claim was 22 (5-74) days for rejection and 11 (1-41) days for reversal. In the rejected and reversed cohorts, 10.2% (n = 111) and 9.8% (n = 90) of patients, respectively, did not receive any paid claim for an antipsychotic after the initial PP1M rejection/reversal. The prevalence of schizophrenia/SCA-related hospitalization during follow-up was similar between patients with a paid (7.4%) and rejected PP1M claim (7.0%; P = 0.689) but higher among patients with a reversed claim (10.8%; P = 0.004). After adjusting for confounders, patients in the reversed cohort were 39% more likely to have a schizophrenia/SCA-related hospitalization than those in the paid cohort (odds ratio = 1.39; 95% CI = 1.03-1.87). CONCLUSIONS: Payer rejection and patient reversal of initial PP1M claims is a form of primary nonadherence and may influence patient trajectory. Data from this study suggest that patient reversal of PP1M may lead to an increased risk of schizophrenia/SCA-related hospitalizations, potentially caused by missed or delayed treatment. Policy initiatives that remove barriers to primary adherence or fulfillment may help improve patients' clinical outcomes.

Adherence, health care utilization, and costs between long-acting injectable and oral antipsychotic medications in South Carolina Medicaid beneficiaries with schizophrenia.

BACKGROUND: Schizophrenia and schizoaffective disorder require long-term antipsychotic treatment with antipsychotic medications, but poor medication adherence can lead to increased health care utilization and costs. Long-acting injectable antipsychotics (LAIs) offer potential therapeutic advantages in that they require less frequent dosing and improved medication adherence. South Carolina has the highest adoption of LAIs among US states, making it an ideal population for comparing the effectiveness of LAIs vs oral antipsychotics (OAPs) in treating schizophrenia or schizoaffective disorder. OBJECTIVE: To evaluate the effect of LAIs compared with OAPs on medication adherence, health care resource utilization, and costs among South Carolina Medicaid beneficiaries with schizophrenia or schizoaffective disorder. METHODS: South Carolina Medicaid beneficiaries with at least 1 claim for an LAI or OAP between January 1, 2015, and December 31, 2018, aged 18 to 65, with at least 2 claims with diagnoses of schizophrenia or schizoaffective disorder were included. Propensity scores (PSs) were calculated using logistic regression adjusting for confounders and predictors of the outcome. We estimated the "average treatment effect on the treated" by employing PS-weighted t-tests and chi-square tests. RESULTS: A total of 3,531 patients met the inclusion criteria, with 1,537 (44.5%) treated with LAIs and 1,994 (56.5%) treated with OAPs. In PS-weighted analyses, the LAI cohort had a greater proportion of days covered than the OAP cohort with a 365-day fixed denominator (69% vs 64%; P < 0.0001), higher medication possession ratio with a variable denominator while on therapy (85% vs 80%; P < 0.0001), and higher persistence (82% vs 64%; P < 0.0001). The average number of inpatient visits and emergency department visits did not significantly differ between cohorts (0.28 hospitalizations, P = 0.90; 3.68 vs 2.96 emergency department visits, P = 0.19). The number of outpatient visits, including visits for medication administration, were greater in the LAI cohort (23.1 [SD 24.2]) vs OAP (16.9 [SD 21.2]; P < 0.0001); however, including the costs for medication administration visits, outpatient costs (per member) were approximately $2,500 lower in the LAI cohort (P < 0.0001). The number of pharmacy visits was greater in the OAP cohort (LAI 21.0 [SD 17.0] vs OAP 23.0 [SD 15.0]; P = 0.006). All-cause total costs were greater in the LAI cohort ($26,025 [SD $29,909]) vs the OAP cohort ($17,291 [SD $25,261]; P < 0.0001) and were driven by the difference in pharmaceutical costs (LAI $15,273 [SD $16,183] vs OAP $4,696 [SD $10,371]; P < 0.0001). CONCLUSIONS: Among South Carolina Medicaid beneficiaries, treatment with LAIs for schizophrenia or schizoaffective disorder was associated with greater medication adherence rates. Patients using LAIs had higher drug costs and total costs, but lower outpatient and total nondrug costs compared with those using OAPs.

Real-world calibration and transportability of the Disease Recovery Evaluation and Modification (DREaM) randomized clinical trial in adult Medicaid beneficiaries with recent-onset schizophrenia.

BACKGROUND: The Disease Recovery Evaluation and Modification study (DREaM; NCT02431702) assessed the benefit of initiating paliperidone palmitate (PP), a long-acting injectable antipsychotic, in patients with recent-onset schizophrenia or schizophreniform disorder. OBJECTIVE: To determine whether reductions in psychiatric hospitalizations with early initiation of PP vs oral antipsychotic (OAP) therapy observed in a DREaM post hoc analysis are transportable to a real-world population of patients with recent-onset schizophrenia. METHODS: Patients enrolled in DREaM were randomized to receive OAP or PP for 9 months, after which OAP recipients were re-randomized to receive OAP or PP for another 9 months. We used this design to form treatment arms: OAP-OAP, OAP-PP, and PP-PP. Inclusion/exclusion criteria were used to identify a Medicaid Managed Care (MMC) OAP-treated cohort of 1,000 patients diagnosed with schizophrenia using IBM Truven databases from 2015 to 2019. The MMC cohort was combined with the subset of patients diagnosed with schizophrenia enrolled in DREaM from US sites (N = 45, 43, and 44 for OAP-OAP, OAP-PP, and PP-PP, respectively). Propensity scores for the MMC cohort were estimated using baseline variables identified via double-lasso regression. Estimated propensity scores were used to weight psychiatric hospitalizations in the DREaM OAP-OAP group and compared with observed MMC OAP cohort psychiatric hospitalizations. After the successful calibration of the DREaM OAP-OAP group, similar approaches were taken for the OAP-PP and PP-PP groups to transport DREaM effects to MMC data. RESULTS: Standardized mean differences in baseline covariates between DREaM treatment arms and MMC groups were substantially reduced after calibration. The 18-month cumulative numbers of psychiatric hospitalizations per patient (SE) were 0.83 (0.14) for the MMC cohort, 0.43 (0.14) for the unweighted OAP-OAP, and 0.80 (0.37) for the calibrated OAP-OAP. The difference between the calibrated OAP-OAP and MMC was not statistically significant (difference, 0.03 [95% CI = -0.67 to 0.81]), indicating successful calibration. The mean difference in 18-month cumulative psychiatric hospitalizations relative to the MMC cohort was -0.77 (95% CI = -1.08 to -0.47) for OAP-PP and -0.83 (95% CI = -1.15 to -0.60) for PP-PP. CONCLUSIONS: Our study demonstrates that results from the DREaM OAP-OAP group reflect psychiatric hospitalizations in a real-world population when calibrated using specific baseline characteristics. Transporting the DREaM effects, we find that using OAP-PP and PP-PP treatment strategies for patients with recent-onset schizophrenia in the MMC population could reduce psychiatric hospitalizations compared with the use of OAP. These findings, along with the potential reduction in associated costs, should be considered when assessing the value of PP formulations. DISCLOSURES: Dr Basu reports consulting fees through Salutis Consulting LLC related to this work. Dr Mavros is a former employee of the Janssen Pharmaceutical Companies of Johnson & Johnson, Inc, and holds stock in the company. Ms Benson, Dr Fu, Ms Patel, and Dr Brown are employees of Janssen Scientific Affairs, LLC, and hold stock in Johnson & Johnson. This research was funded by Janssen Scientific Affairs, LLC. The sponsor was involved in the study design; collection, analysis, and interpretation of data; and development and review of the manuscript. All authors had full access to the study data and take responsibility for data integrity and the accuracy of the analyses. All authors provided direction and comments on the manuscript, reviewed and approved the final version prior to submission, made the final decision about where to publish these data, and approved submission to this journal.

Continuity of care among patients newly initiated on second-generation oral or long-acting injectable antipsychotics during a schizophrenia-related inpatient stay.

BACKGROUND: Maintaining continuity of care after schizophrenia-related hospitalization is challenging for patients and healthcare providers and systems. Prior evidence suggests that second-generation long-acting injectable antipsychotics (SGLAIs) may reduce the risk of treatment nonadherence and readmission versus oral atypical antipsychotics (OAAs). Therefore, quality measures were compared between patients initiated on SGLAIs and OAAs in the United States. METHODS: Adults newly initiated on an SGLAI or OAA during a schizophrenia-related inpatient stay were identified in HealthVerity databases (01/2015-12/2020); the index date was the hospital discharge date. Patients had continuous health insurance coverage for pharmacy and medical services for 6 months pre-admission and post-discharge from the inpatient stay and ≥1 pharmacy or medical claim (i.e. treatment as indicated by the observed insurance claims) for an antipsychotic other than the index SGLAI or OAA in the 6 months pre-admission. Antipsychotic use and adherence, and schizophrenia-related readmissions and outpatient visits were compared during the 6-month period post-discharge. Characteristics between cohorts were balanced using inverse probability weights. RESULTS: Post-discharge, only 36.9% and 40.7% of weighted SGLAI (N = 466) and OAA (N = 517) patients had ≥1 pharmacy or medical claim for the antipsychotic initiated during the inpatient stay, among whom SGLAI patients were 4.4 times more likely to be adherent to that antipsychotic compared to OAA patients (p < .001). Additionally, SGLAI patients were 2.3 and 3.0 times more likely to have a pharmacy or medical claim for and be adherent to any antipsychotic relative to OAA patients (including index antipsychotic; all p < .001). Within 7 and 30 days post-discharge, 1.7% and 13.0% of SGLAI patients and 4.1% and 12.6% of OAA patients had a readmission. Further, SGLAI patients were 51% more likely to have an outpatient visit compared to OAA patients (p = .044). CONCLUSIONS: Less than half of patients initiated on antipsychotics during a schizophrenia-related inpatient stay continued the same treatment post-discharge. However, SGLAI patients were more likely to be adherent to the initiated antipsychotic and to have an outpatient visit, which may suggest improved continuity of care post-discharge relative to OAA patients.

Projecting the economic outcomes of switching patients with schizophrenia from oral atypical antipsychotics to once-monthly, once-every-3-months, and once-every-6-months paliperidone palmitate.

BACKGROUND: Among patients with schizophrenia, nonadherence to oral atypical antipsychotics (OAAs) leads to increased risk of relapses, which entails substantial economic burden. OBJECTIVE: To evaluate the impact on health care costs and relapse rates of switching patients with schizophrenia from OAAs to once-monthly paliperidone palmitate (PP1M), with subsequent transitions to once-every-3-months (PP3M) and once-every-6-months paliperidone palmitate (PP6M). METHODS: A 36-month Markov model was developed from a Medicaid payer's perspective. Two non-mutually exclusive subpopulations of adults with schizophrenia who were nonadherent to OAAs were considered: (1) recently relapsed and (2) young adults (aged 18-35). Patients were assumed nonadherent to OAAs until switching treatments, which was permissible multiple times during the 36-month period. Patients switching to PP1M could subsequently transition to PP3M and PP6M. Relapse rates were assumed consistent across treatments based on patients' adherence. Model inputs were literature based. PP6M transition rates were assumed similar to PP3M. Cost savings were reported at the plan level and per patient switched. RESULTS: In a hypothetical health plan of 1 million Medicaid beneficiaries, an estimated 10,053 adults with schizophrenia were nonadherent to OAAs, among whom 7,454 were recently relapsed and 4,002 were young adults. Switching 5% of recently relapsed adults (N = 373) from OAAs to PP1M prior to subsequent relapse resulted in 541 relapses avoided and plan-level savings of $8.2M after 3 years. Incorporating transitions to PP3M/PP6M increased net savings to $9.1M and 631 relapses were avoided. Among young adults, switching 5% (N = 200) from OAAs to PP1M saved $1.8M at the plan level with 178 relapses avoided after 3 years. Including transitions to PP3M/PP6M, 3-year plan-level savings were $2.0M with 223 relapses avoided. Per recently relapsed patient switched to PP1M, and subsequently to PP3M/PP6M, cumulative 3-year cost savings were $22,100 and $24,300, respectively. Among young adults, corresponding 3-year cost savings per patient were $8,900 and $9,800. CONCLUSIONS: Switching nonadherent patients from OAAs to PP1M results in substantial cost savings and reduces relapse rates. Incorporating transitions to PP3M/PP6M leads to incremental cost savings and additional relapses avoided. DISCLOSURES: Financial support for this research was provided by Janssen Scientific Affairs, LLC. Ms Morrison, Ms Ghelerter, Ms Vermette-Laforme, Mr Lefebvre, and Mr Pilon 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. Dr Lin and Ms Benson are employees of Janssen Scientific Affairs, LLC., and stockholders of Johnson & Johnson.

A Cross-Sectional Study of Patient Out-of-Pocket Costs for Antipsychotics Among Medicaid Beneficiaries with Schizophrenia.

BACKGROUND: Patient affordability is an important nonclinical consideration for treatment access among patients with schizophrenia. OBJECTIVE: This study evaluated and measured out-of-pocket (OOP) costs for antipsychotics (APs) among Medicaid beneficiaries with schizophrenia. METHODS: Adults with a schizophrenia diagnosis, ≥ 1 AP claim, and continuous Medicaid eligibility were identified in the MarketScan® Medicaid Database (1 January 2018-31 December 2018). OOP AP pharmacy costs ($US 2019) were normalized for a 30-day supply. Results were descriptively reported by route of administration [ROA; orals (OAPs), long-acting injectables (LAIs)], generic/branded status within ROAs, and dosing schedule within LAIs. The proportion of total (pharmacy and medical) OOP costs AP-attributable was described. RESULTS: In 2018, 48,656 Medicaid beneficiaries with schizophrenia were identified (mean age 46.7 years, 41.1% female, 43.4% Black). Mean annual total OOP costs were $59.97, $6.65 of which was AP attributable. Overall, 39.2%, 38.3%, and 42.3% of beneficiaries with a corresponding claim had OOP costs > $0 for any AP, OAP, and LAI, respectively. Mean OOP costs per patient per 30-day claim (PPPC) were $0.64 for OAPs and $0.86 for LAIs. By LAI dosing schedule, mean OOP costs PPPC were $0.95, $0.90, $0.57, and $0.39 for twice-monthly, monthly, once-every-2-months, and once-every-3-months LAIs, respectively. Across ROAs and generic/branded status, projected OOP AP costs per-patient-per-year for beneficiaries assumed fully adherent ranged from $4.52 to $13.70, representing < 25% of total OOP costs. CONCLUSION: OOP AP costs for Medicaid beneficiaries represented a small fraction of total OOP costs. LAIs with longer dosing schedules had numerically lower mean OOP costs, which were lowest for once-every-3-months LAIs among all APs.

Antipsychotic utilization, healthcare resource use and costs, and quality of care among fee-for-service Medicare beneficiaries with schizophrenia in the United States.

BACKGROUND: No research to date has examined antipsychotic (AP) use, healthcare resource use (HRU), costs, and quality of care among those with schizophrenia in the Medicare program despite it serving as the primary payer for half of individuals with schizophrenia in the US. OBJECTIVES: To provide national estimates and assess regional variation in AP treatment utilization, HRU, costs, and quality measures among Medicare beneficiaries with schizophrenia. METHODS: Cross-sectional descriptive analysis of 100% Medicare claims data from 2019. The sample included all adult Medicare beneficiaries with continuous fee-for-service coverage and ≥1 inpatient and/or ≥2 outpatient claims with a diagnosis for schizophrenia in 2019. Summary statistics on AP use; HRU and cost; and quality measures were reported at the national, state, and county levels. Regional variation was measured using the coefficient of variation (CoV). RESULTS: We identified 314,888 beneficiaries with schizophrenia. About 91% used any AP; 20% used any long-acting injectable antipsychotic (LAI); and 14% used atypical LAIs. About 28% of beneficiaries had ≥1 hospitalization and 47% had ≥1 emergency room (ER) visits, the vast majority of which were related to mental health (MH). Total annual all-cause, MH, and schizophrenia-related costs were $23,662, $15,000 and $12,109, respectively. Among those with hospitalizations, 18.4% and 27.3% had readmission within 7 and 30 days and 56% and 67% had a physician visit and AP fill within 30 days post-discharge, respectively. Overall, 81% of beneficiaries were deemed adherent to their AP medications. Larger interstate variations were observed in LAI use than AP use (CoV: 0.21 vs 0.02). County-level variations were larger than state-level variations for all measures. CONCLUSIONS: In this first study examining a national sample of Medicare beneficiaries with schizophrenia, we found low utilization rates of LAIs and high levels of hospital admissions/readmissions and ER visits. State and county-level variations were also found in these measures.

Budget impact of introducing once-every-6-months paliperidone palmitate in US health care plans.

BACKGROUND: In the United States, most patients with schizophrenia have Medicaid coverage. Antipsychotic treatments are the cornerstone of schizophrenia management; most patients are treated with daily oral antipsychotics but struggle with medication adherence. Evidence suggests that medication adherence is inversely correlated with dosing frequency. Once-monthly paliperidone palmitate (PP) has been demonstrated to improve adherence compared with oral antipsychotics; transitioning to once-every-3-months PP (PP3M) further improved adherence. In 2021, once-every-6-months PP (PP6M) was approved by the US Food and Drug Administration to provide even longer between-dose intervals. Public health stakeholders who aim to improve medication adherence are interested in understanding how introducing PP6M to the formulary will impact the budget. OBJECTIVE: To evaluate the budget impact of introducing PP6M to the formulary from the perspectives of a hypothetical US multistate health care payer and state Medicaid programs using California, Georgia, and Ohio as examples. METHODS: The budget impact model was developed from a payer perspective, comparing the reference scenario (without PP6M in the market) with a new scenario (with PP6M). The study population included patients with schizophrenia who were eligible to receive PP6M. Market shares were assigned to the reference and new market scenarios. Efficacy was measured by the relative risk of relapse while receiving treatment. Adherence effects were included in the model and affected costs of treatment and relapse rates. A deterministic 1-way sensitivity analysis was performed. RESULTS: Base-case results for a multistate payer with 1 million members demonstrate that adding PP6M to the market results in total incremental plan-level costs ranging from $7,747 in year 1 to $11,501 in year 5. Increased drug costs were offset by administration and relapse cost savings ($105 and $881 in year 5, respectively). The average incremental cost per treated patient per year was stable at $180.06 for each year, and the incremental cost per member per month stayed below $0.01 for each year. The results of the model from the state-level Medicaid scenarios are broadly similar to those of the multistate base-case perspective. The 1-way sensitivity analysis demonstrated the model is most sensitive to the per-package costs of PP6M and PP3M, along with the proportion of patients fully adherent with PP3M. CONCLUSIONS: The budget impact of introducing PP6M as a treatment option is minimal. With the expected cost offsets from reduced administration and relapse costs due to adherence benefits, these results suggest that PP6M can be a viable treatment option from a clinical and a budgetary perspective. DISCLOSURES: This study was funded by Janssen Scientific Affairs, LLC. The study sponsor provided funds to Xcenda and ApotheCom for medical writing, editorial support, and submission of the manuscript. Hilary Phelps was an employee of Janssen Global Services, LLC, at the time of the development and finalization of the manuscript. Alex Keenan is an employee of Janssen Global Services, LLC, and holds stock in Johnson & Johnson, Inc. Dee Lin and Carmela Benson are employees of Janssen Scientific Affairs, LLC, and hold stock in Johnson & Johnson, Inc. Aditya Raju was an employee of Xcenda at the time of the development and finalization of the manuscript, and Danmeng Huang is an employee of Xcenda, a health care consulting firm that was contracted by Janssen Scientific Affairs, LLC. Chih-Yuan Cheng is an employee of Janssen NV.

Comparison of clinical outcomes in patients with schizophrenia following different long-acting injectable event-driven initiation strategies.

This retrospective study evaluated the benefit of following different long-acting injectable (LAI) initiation strategies based on the timing of behavioral and clinical events among Medicaid beneficiaries with schizophrenia. Adults with schizophrenia initiating oral antipsychotics (OAPs) after 12 months without antipsychotic use or schizophrenia-related inpatient/emergency room (ER) visits (index date) were identified. Patients were categorized into four event-driven LAI initiation strategy cohorts based on observed sequences of behavioral (i.e., OAP adherence) and clinical (i.e., schizophrenia-related inpatient/ER visits) events between index and LAI initiation or censoring-strategy #1: adherent to OAPs without schizophrenia-related inpatient/ER visits; strategy #2: nonadherent to OAPs without schizophrenia-related inpatient/ER visits; strategy #3: one schizophrenia-related inpatient/ER visit; strategy #4: ≥2 schizophrenia-related inpatient/ER visits. Clinical outcomes (i.e., all-cause inpatient/ER visits) were evaluated between OAP initiation and end of follow-up. Comparisons between LAI initiation strategy cohorts were conducted using a dynamic marginal structural model adjusting for baseline characteristics and time-varying confounders. Among 13,444 eligible patients, 13.1%, 53.6%, 15.7%, and 17.6% were following strategies #1-4, respectively; of these, 21.9%, 4.3%, 9.2%, and 6.5% started an LAI (the remaining were censored). Strategy #1 was associated with a greater clinical benefit, with 43%, 69%, and 80% fewer inpatient days (all p < 0.05); and 57%, 59%, and 79% fewer ER visits (all p < 0.01) vs strategies #2-4, respectively; the clinical benefit was also observed for strategy #2 vs #3-4. Therefore, starting an LAI prior to OAP nonadherence or occurrence of a schizophrenia-related inpatient/ER visit was associated with fewer all-cause inpatient days of inpatient stay and ER visits.