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INVEGA SUSTENNA® (paliperidone palmitate)

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INVEGA SUSTENNA - Healthcare Resource Utilization, Cost Outcomes, and Treatment Patterns

Last Updated: 10/02/2024

SUMMARY

Data from real-world studies showed reduced probability of schizophrenia relapse¹^-⁵ and reduced utilization of hospitalization and/or ER services¹^-³^,⁶^-²⁸ following the initiation of INVEGA SUSTENNA vs oral antipsychotics (OAPs).
Numerous studies demonstrated significant reduction of medical costs that partially or fully offset the increased pharmacy cost⁴^,⁶^,¹²^-¹⁵^,¹⁷^-²¹^,²⁵^,²⁶, and two others found that treatment with INVEGA SUSTENNA vs OAPs was associated with total healthcare cost savings.⁷^,⁸
Improvement in medication adherence and persistence were consistently observed with INVEGA SUSTENNA compared to OAPs in general patient population and subpopulations, including patients with prior schizophrenia relapses, co-occurring substance abuse, and other comorbidities such as cardiovascular disease and obesity.⁷^,⁹^,²¹^,²²^,²⁴^-²⁶^,²⁹^-³¹
INVEGA SUSTENNA has also demonstrated improvement in socioeconomic outcomes, including reduction of homelessness and reincarceration.⁷^,³²

BACKGROUND

In economic impact alone, the burden of schizophrenia is tremendous. A cost-of-illness study estimated that in 2013, schizophrenia was responsible for a total excess cost to society of approximately $155.7 billion based upon an estimated schizophrenia population of 3,477,417 (prevalence rate: 1.1%).³³ Besides high healthcare utilization and costs, patients with schizophrenia also face substantial non-healthcare societal burden.³⁴

CLINICAL DATA

US Healthcare Resource Utilization, Cost, and Treatment Patterns

Studies assessing treatment patterns, including medication adherence and persistence, healthcare resource utilization and costs following treatment with INVEGA SUSTENNA vs oral antipsychotics have been conducted in patients treated for schizophrenia. Outcomes of these studies, focused on all-cause results, are summarized in the Table: US Healthcare Resource Utilization, Cost Outcomes, and Treatment Patterns – INVEGA SUSTENNA vs Oral Antipsychotics.

US Healthcare Resource Utilization, Cost Outcomes, and Treatment Patterns – INVEGA SUSTENNA vs Oral Antipsychotics

Schizophrenia
Patel et al (2024)⁵ conducted a real-world, retrospective, observational cohort study in adult patients with schizophrenia with Medicare Advantage claims to compare the clinical outcomes of newly initiated INVEGA SUSTENNA vs FGA-LAIs. The date of the first INVEGA SUSTENNA or FG-LAI claim was considered the study index date. The primary outcome was relapse (defined as a composite measure of schizophrenia-related hospitalization or ED visits). Propensity score-based standardized mortality ratio weighing was applied to reduce confounding factors. Sensitivity analysis was performed in patient subgroups stratified as per socioeconomic variables (race, education, and household income), dual Medicare/Medicaid coverage, and different LAI registered during follow-up than on the index date. *Data Source:* Optum’s de-identified Clinformatics^® Data Mart database (January 2009 to June 2023) *Patient Population:* In the unweighted cohorts, 870 patients (mean age, 52.4 years; female, 43.3%; Black, 27.9%) were included in the newly-initiated INVEGA SUSTENNA group and 1801 patients (mean age, 58.8 years; female, 48.8%; Black, 30.4%) in the newly-initiated FGA-LAI group. In the weighed cohorts, 870 and 866 patients with comparable baseline characteristics were included in the INVEGA SUSTENNA and FGA-LAI groups, respectively. The median (IQR) follow-up duration for the INVEGA SUSTENNA group was 654 (295-1362) days, and the FGA-LAI group was 516 (210-1160) days. *Outcome:* The weighted relapse rate was lower in the INVEGA SUSTENNA group vs the FGA-LAI group (35.3 vs 62.8 per 100 PY; IRR [95% CI], 0.56 [0.40-0.71]). The weighted median time to first relapse was significantly longer in the INVEGA SUSTENNA group vs the FGA-LAI group (1772 vs 816 days; P<0.0001). Additionally, patients initiated on INVEGA SUSTENNA had a 40% lower risk of first relapse vs those initiated on FGA-LAI (weighted HR, 0.60; 95% CI, 0.51-0.69). Sensitivity analysis in patient subgroups was consistent with the overall study population. *Conclusion:* Among Medicare Advantage patients with schizophrenia, the relapse rate in LAI-naïve patients initiated with INVEGA SUSTENNA was significantly lower compared to treatment with FGA-LAIs.
Li et al (2024)^28,35,36 conducted a real-world, retrospective study in adult patients with schizophrenia with Medicare claims for ≥1 antipsychotic to compare the effectiveness of OAPs vs LAIs, including INVEGA SUSTENNA and INVEGA TRINZA. The date of the first antipsychotic prescription was considered as the study index date. The outcomes included treatment failure and relapse. Treatment failure was a composite outcome of psychiatric hospitalization, antipsychotic discontinuation, suicide attempts, and death. Relapse was defined as an inpatient admission or ER visit with a diagnosis of schizophrenia. Oral risperidone, LAI risperidone, and LAI aripiprazole was used as the reference antipsychotic for each analysis. *Data Source:* National Chronic Conditions Warehouse (January 1, 2006 to December 31, 2019) *Patient Population:* 152,835 patients were included (mean age, 53.5 years; male, 54.0%; White, 61.5%). *Outcomes:* Relative to oral risperidone, outcomes favored INVEGA SUSTENNA and INVEGA TRINZA for each endpoint analyzed, including treatment failure (INVEGA SUSTENNA: HR, 0.75; 95% CI, 0.73-0.78 and INVEGA TRINZA: HR, 0.53; 95% CI, 0.47-0.60), psychiatric hospitalization (INVEGA SUSTENNA: HR, 0.78; 95% CI, 0.75-0.80 and INVEGA TRINZA: HR, 0.76; 95% CI, 0.66-0.88), treatment discontinuation (INVEGA SUSTENNA: HR, 0.59; 95% CI, 0.55-0.63 and INVEGA TRINZA: HR, 0.19; 95% CI, 0.15-0.24), and relapse (INVEGA SUSTENNA: HR, 0.83; 95% CI, 0.81-0.85 and INVEGA TRINZA: HR, 0.75; 95% CI, 0.67-0.83). Relative to LAI risperidone, outcomes favored INVEGA SUSTENNA and INVEGA TRINZA for each endpoint analyzed, including treatment failure (INVEGA SUSTENNA: HR, 0.95; 95% CI 0.92-0.99, and INVEGA TRINZA: HR, 0.67; 95% CI, 0.60-0.76), psychiatric hospitalization (INVEGA SUSTENNA: HR, 0.93; 95% CI, 0.89-0.97 and INVEGA TRINZA: HR, 0.91; 95% CI, 0.78-1.05), treatment discontinuation (INVEGA SUSTENNA: HR, 0.94; 95% CI, 0.86-1.02 and INVEGA TRINZA: HR, 0.31; 95% CI, 0.24-0.39), and relapse (INVEGA SUSTENNA: HR, 0.93; 95% CI, 0.89-0.96 and INVEGA TRINZA: HR, 0.83; 95% CI, 0.75-0.93). Relative to LAI aripiprazole, outcomes favored INVEGA SUSTENNA and INVEGA TRINZA for each endpoint analyzed, including treatment failure (INVEGA SUSTENNA: HR, 0.88; 95% CI, 0.83-0.94 and INVEGA TRINZA: HR, 0.62; 95% CI, 0.55-0.71), psychiatric hospitalization (INVEGA SUSTENNA: HR, 0.86; 95% CI, 0.80-0.92 and INVEGA TRINZA: HR, 0.84; 95% CI, 0.72-0.98), treatment discontinuation (INVEGA SUSTENNA: HR, 0.87; 95% CI, 0.77-0.99 and INVEGA TRINZA: HR, 0.29; 95% CI, 0.22-0.37), and relapse (INVEGA SUSTENNA: HR, 0.93; 95% CI, 0.88-0.98 and INVEGA TRINZA: HR, 0.84; 95% CI, 0.74-0.94). *Conclusion*: Compared to oral risperidone, LAI risperidone, and LAI aripiprazole, treatment with INVEGA SUSTENNA and INVEGA TRINZA was associated with lower risks for all outcomes and INVEGA TRINZA was associated with the lowest risk of treatment failure.
Basu et al (2021)³⁵ conducted post-hoc analyses of HRU and costs on those who participated in the DREaM study, which was a 20-month prospective study evaluating time to first treatment failure (TtFTF) of INVEGA SUSTENNA or INVEGA TRINZA vs oral antipsychotics (OAPs) in patients with recent onset schizophrenia or schizophreniform disorder. *Patient Population:* A total of 181 adults with recent-onset schizophrenia were included and INVEGA SUSTENNA/INVEGA TRINZA (n=61), OAP/OAP (n=61), and OAP/PP (n=59). Of those, the percentage of patients with a duration of antipsychotic use <6 months for INVEGA SUSTENNA/INVEGA TRINZA, OAP/OAP, and OAP/PP was 45%, 46%, and 52%, respectively. *HRU:* Compared to the OAP/OAP group, the average number of psychiatric hospitalizations for patients in the INVEGA SUSTENNA/INVEGA TRINZA and OAP/PP groups was lower by 0.28 (95% CI: –0.51 to –0.08) and 0.27 (95% CI: –0.50 to –0.04), respectively, with a greater reduction for patients with <6 vs ≥6 months of prior antipsychotic therapy. There was a statistically significant reduction in psychiatric hospitalizations with INVEGA SUSTENNA/INVEGA TRINZA compared with OAP/OAP in the first 9 months of treatment. *Healthcare Costs:* Compared with OAP/OAP, patients in the INVEGA SUSTENNA/INVEGA TRINZA and OAP/PP groups had lower total healthcare costs by $2,867 (95% CI: –$5,133 to –$750) and $2,789 (95% CI: –$5155 to –$701) per patient, respectively, and significant cost reductions with <6 months prior antipsychotic use and cost savings were primarily driven by decreases in psychiatric hospitalizations. *Conclusion:* Earlier and sustained treatment with INVEGA SUSTENNA/INVEGA TRINZA for 18 months was associated with significant reductions in psychiatric hospitalizations and associated costs compared with patients treated with OAP/OAP with recent-onset schizophrenia and greatest decreases observed in patients with <6 month history of prior antipsychotic use.
Patel et al (2021)³⁶ conducted a retrospective longitudinal cohort study comparing HRU, including the risk of schizophrenia-related relapses, and healthcare costs in Medicaid patients who initiated INVEGA SUSTENNA vs a new OAAP after a recent schizophrenia-related relapse. A recent schizophrenia relapse was defined based on an inpatient or ER claim with a diagnosis code for schizophrenia within 30 days prior to the date of INVEGA SUSTENNA or new OAAP initiation. *Data Source: Medicaid data from Iowa (Q1 1998 to Q1 2017), Kansas (Q1 2001 to Q1 2018), Mississippi (Q1 2006 to Q1 2018), Missouri (Q1 1997 to Q1 2018), New Jersey (Q1 1997 to Q1 2014), and Wisconsin (Q1 2004 to Q4 2013). HRU:* Patients in the INVEGA SUSTENNA cohort had 42% lower odds of having ≥1 all-cause inpatient admission than those in the matched OAAP cohort (P<0.001). The INVEGA SUSTENNA cohort had 29% fewer inpatient admissions PPPY (P=0.004) and 37% fewer days spent PPPY in an inpatient setting compared to the OAPP cohort (P=0.004). *Healthcare Costs:* Patients in the INVEGA SUSTENNA cohort had significantly lower all-cause PPPY medical costs compared to the matched OAAP cohort (mean cost difference [MCD]=-$6,273; P=0.028). Patients in the INVEGA SUSTENNA cohort had lower all-cause PPPY inpatient costs (MCD=-$3,167; P=0.052), lower all-cause PPPY outpatient costs (MCD=-$745; P=0.024), and numerically lower all-cause PPPY long-term care costs (MCD=-$2,178; P=0.104). Lower medical costs offset higher PPPY pharmacy costs ($4,770, P<0.001) resulting in a statistically non-significant difference in total healthcare costs between the INVEGA SUSTENNA and OAAP cohorts (MCD=-$1,503 PPPY; P=0.621). *Conclusion:* Patients treated with INVEGA SUSTENNA after a recent schizophrenia-related relapse were less likely to have subsequent schizophrenia-related relapses compared to patients treated with an OAAP. Higher pharmacy costs were offset by lower medical costs in the INVEGA SUSTENNA cohort, resulting in similar total healthcare costs compared to the OAAP cohort.
Lin et al (2020)³⁷ conducted a systematic literature review of peer-reviewed English language articles (1/1/2010 – 2/10/2020) to compare rates of hospitalizations and ER admissions, healthcare costs, and medication adherence in patients with schizophrenia initiated on an LAI vs an OA or before and after initiation of LAI reported in real-world studies in the US. *HRU:* Patients initiated on an LAI had lower odds of being hospitalized compared with an oral antipsychotic (n=7; OR [95% CI] 0.62 [0.54–0.71]). Patients initiated on LAIs had 25% fewer all-cause hospitalizations vs oral antipsychotics (n=9; incidence rate ratios (IRR) [95% CI] 0.75 [0.65–0.88]). Patients initiated on an LAI had 14% fewer all-cause ER admissions vs oral antipsychotics (n=6; IRR [95% CI] 0.86 [0.77–0.97]) *Adherence:* Patients initiated on an LAI were 89% more likely to be adherent to medication (n=9; OR [95% CI] 1.89 [1.52–2.35]) and had 9% higher mean PDC compared to oral antipsychotics (n=9; 95% CI: 2-15) *All-Cause Healthcare Costs:* No significant difference in total all-cause healthcare costs PPPY between patients initiated on an LAI vs an OA (n=7; mean difference [MD] [95% CI] $327 [− $1,565 to $2,219]). Higher PPPY pharmacy costs associated with initiation of LAI (n=6; MD [95% CI] $5,603 [$3,799–$7,407]) were offset by lower PPPY medical costs (MD [95% CI] − $5,404 [−7,745 to −3,064]) *Sensitivity Analysis Comparing INVEGA SUSTENNA vs OAPs: Patients initiated on INVEGA SUSTENNA had fewer all-cause hospitalizations (n=6; IRR [95% CI] 0.74 [0.62–0.89]) and fewer ER admissions (n=6; IRR [95% CI] 0.82 [0.69–0.98]) compared to patients initiated on oral antipsychotics. INVEGA SUSTENNA was associated with greater likelihood of medication adherence as compared to oral antipsychotics (n=8; OR [95% CI] 1.93 [1.54–2.42]). Conclusion:* Treatment with LAIs may reduce hospitalizations and ER admissions, while remaining cost neutral compared to treatment with oral antipsychotics.
Patel et al (2019)⁴ conducted a retrospective longitudinal cohort study comparing HRU, including the risk of schizophrenia-related relapses, and healthcare costs in Medicaid patients who initiated INVEGA SUSTENNA vs a new OAAP after a recent schizophrenia-related relapse. *Data Source: Medicaid data from Iowa (Q1 1998 to Q1 2017), Kansas (Q1 2001 to Q1 2018), Mississippi (Q1 2006 to Q1 2018), Missouri (Q1 1997 to Q1 2018), New Jersey (Q1 1997 to Q1 2014), and Wisconsin (Q1 2004 to Q4 2013) Sample Size: INVEGA SUSTENNA: n=208; OAAP: n=624; Differences in patient characteristics were adjusted through 1:3 propensity score matching Subsequent relapses:* 61.1% of patients in the INVEGA SUSTENNA cohort had ≥1 subsequent schizophrenia-related relapse vs 83.2% in the OAAP cohort (OR: 0.32; P<0.001). Patients on INVEGA SUSTENNA had an average of 1.89 (SD, 2.76) subsequent schizophrenia-related relapses compared with 2.80 (SD, 3.40) on OAAP (RR: 0.67; P=0.004) *HRU:* INVEGA SUSTENNA cohort patients had 36% lower all-cause inpatient admissions (P=0.004), 40% fewer days spent in an inpatient setting (P=0.004), 23% fewer ER visits (P=0.048), and a similar number of outpatient and other visits compared to the OAAP cohort. *Healthcare Costs:* Patients in INVEGA SUSTENNA cohort had a non-significant decrease of $5,499 in all-cause PPPY medical costs (P=0.072), which offset the $4,826 increase in pharmacy costs PPPY (P<0.001). There was a numerical but not statistically significant decrease in total PPPY healthcare costs of $673 (P=0.870) in the INVEGA SUSTENNA cohort as compared to OAAP cohort. *Conclusion:* INVEGA SUSTENNA initiation is associated with lower likelihood of subsequent relapse and reduced inpatient and ER utilization compared to OAAPs in Medicaid patients with SCZ who had a recent relapse.
Manjelievskaia et al (2018)²⁴ conducted a retrospective cohort study comparing treatment patterns and HRU in patients treated with INVEGA SUSTENNA vs OAAPs with a focus on young adults (18-35 years). *Data Sources:* US - Truven Health MarketScan Medicaid Multi-State Database (January 1, 2010 –December 31, 2014) *Sample Size:* A total of 15,598 met the study criteria, among which 6,250 were aged 18-35 (439 INVEGA SUSTENNA patients and 5,811 OAAP patients) *Treatment Patterns:* During follow-up, young adults treated with INVEGA SUSTENNA had a higher duration of continuous treatment exposure (168.2 vs 132.5 days, P=0.004), better adherence on the index medication (PDC ≥80%: 19.0% vs 17.1%, P<0.049) and any antipsychotic drug (29.6% vs 23.5%, P<0.001) compared to OAAP young adult patients. *HRU:* Young adults treated with INVEGA SUSTENNA were 37% less likely to have an all-cause inpatient admission (OR: 0.63; 95% CI: 0.53-0.74) and 33% less likely to have an ER visit (OR: 0.67; 95% CI: 0.55-0.81) compared to OAAP young adult patients, but 27% more likely to have an all-cause outpatient office visit (OR: 1.27; 95% CI: 1.02–1.56). *Healthcare Costs: Total costs were not significantly different between INVEGA SUSTENNA and OAAP groups, both in overall and young adult cohorts. Conclusion:* Young adults (aged 18-35 years) with schizophrenia treated with INVEGA SUSTENNA reported higher medication adherence and fewer hospitalizations in comparison to patients treated with OAAPs.
Pilon et al (2018)³⁸ conducted a retrospective cohort study comparing rehospitalization patterns in hospitalized patients with schizophrenia aged 18-35 who were treated with INVEGA SUSTENNA or OAAP. *Data Sources: The Premier Perspective Comparative Hospital database from 01/2009-12/2016 Sample Size: In the overall population, 199,690 patients had hospitalizations, 6,980 and 195,793 patients with INVEGA SUSTENNA and OAAP index hospitalizations, respectively. In the young adult population, there were 3,791 and 96,502 index hospitalizations during which INVEGA SUSTENNA or OAAP were used to treat patients, respectively. HRU: In the young adult population, prior to multivariate adjustment, the rates of index hospitalizations resulting in all-cause and schizophrenia-related rehospitalization were consistently lower for INVEGA SUSTENNA relative to OAAP index hospitalizations (ie, all-cause rehospitalization at 30 days: 11.8% vs 15.5%, at 60 days: 16.7% vs 20.6%, and at 90 days: 21% vs 24.2%). Using a multivariate model for the young adult population, the odds of all-cause rehospitalization were significantly lower by 27% for patients with an INVEGA SUSTENNA index hospitalization after 30 and 60 days, and by 25% after 90 days of follow-up compared to patients with an OAAP index hospitalization (all P-values<0.001). In the overall population, trends were similar with consistently lower rehospitalization rate after discharge from an INVEGA SUSTENNA index hospitalization compared to an OAAP index hospitalization (ie, all-cause rehospitalization at 30 days: 13.8% vs 17.6%, at 60 days: 19.2% vs 23.5%, and at 90 days: 23.7% vs 27.6%). In the overall population using a multivariate model, similar trends were observed: the odds of all-cause rehospitalization were significantly lower by 21% for patients with an INVEGA SUSTENNA index hospitalization after 30 days, by 22% after 60 days, and by 19% after 90 days of follow-up compared to patients with an OAAP index hospitalization (all P-values<0.001). Conclusion:* Young adults (aged 18-35 years) with schizophrenia treated with INVEGA SUSTENNA had lower odds of rehospitalization in 30 to 90 days after discharge compared to those treated with OAAP.
Joshi et al (2018)¹⁸ conducted a retrospective longitudinal study assessing and comparing adherence, resource utilization and cost among eligible patients enrolled in the Medicare Advantage Prescription Drug Plan and treated with INVEGA SUSTENNA or OAAP for schizophrenia (baseline characteristics were adjusted with IPTW methods and were calculated utilizing the PS which defined the probability of being in a treatment group given the observed covariates). *Data Sources:* Healthcare claims from Humana’s fully insured commercial and Medicare databases (Northeast; Midwest; South; West) from 01/01/2009-09/30/2015 Sample size: INVEGA SUSTENNA: n=295; OAAP: n=2,296 *HRU: The proportion of patients with all-cause hospitalization was significantly lower in the INVEGA SUSTENNA cohort compared to the OAAP cohort (34.1% vs 39.1%; P=0.013). The average number of hospitalizations was significantly lower for patients in the INVEGA SUSTENNA cohort, compared to the OAAP cohort (0.62 vs 0.85; P=0.002). For patients with a hospitalization, the average inpatient days were significantly lower for patients in the INVEGA SUSTENNA cohort compared with the OAAP cohort (4.73 vs 7.28; P=0.0014). Healthcare costs: Patients using INVEGA SUSTENNA had lower medical costs ($11,095; 95% CI: $10,374–11,867 vs $15,551; 95% CI: $14,584–16,583), but higher pharmacy costs ($14,787; 95% CI: $14,117–15,488 vs $5,781; 95% CI: $5,530–6,043) Conclusion:* Medicare patients with schizophrenia treated with INVEGA SUSTENNA had greater adherence, lower treatment discontinuation, fewer hospitalizations, and lower medical costs that offset the higher pharmacy costs, compared to those using OAAPs.
Pilon et al (2017)³⁹ conducted a retrospective longitudinal cohort study comparing adherence, HRU and Medicaid spending between patients with schizophrenia, initiated on INVEGA SUSTENNA vs OAAPs over a 12-month follow-up period. The study focused on both the overall schizophrenia population and the recently diagnosed population defined by age. IPTW was utilized to balance baseline demographic, clinical characteristics, and baseline healthcare costs. *Data Sources: Health claims from New Jersey (2008Q3-2014Q1), Iowa (2008Q3-2015Q1), Missouri (2008Q3-2015Q1), Mississippi (2008Q3-2015Q1) and Kansas (2008Q3-2015Q1) Medicaid databases Sample Size after IPTW: Overall cohort* (INVEGA SUSTENNA: n=11,612; OAAP patients: n=12,688); recently diagnosed cohort, aged 18–25 yrs (INVEGA SUSTENNA: n=1,107; OAAP patients: n=1,288) *Treatment Patterns: Overall Cohort: INVEGA SUSTENNA vs OAAP patients had a longer duration of continuous treatment with the index agent (mean days: 215.8 vs 194.4, respectively; P<0.001), while being less likely to use any additional antipsychotic agent (59.1% vs 64.8%, respectively; P<0.001), or utilize antipsychotic polypharmacy (23.6% vs 29.2%, respectively; P<0.001). INVEGA SUSTENNA vs OAAP patients were also more likely to be adherent to index medication (PDC ≥80%: 26.7% vs 22.7%, respectively; P<0.001) and more likely to persist on the index medication (no gap ≥60 days: 38.7% vs 29.0%, respectively; P<0.001) after 12 months of follow-up. Recently Diagnosed (aged: 18-25 yrs): Similar treatment patterns and adherence were observed in this subgroup of patients but to a greater magnitude. After 12 months of follow-up, INVEGA SUSTENNA vs OAAP patients were more likely to be adherent to the index medication (PDC ≥80%: 28.8% vs 21.1%, respectively; P<0.001) and more likely to persist on the index medication (no gap ≥60 days: 38.7% vs 27.6%, respectively; P<0.001). HRU: Overall Cohort:* INVEGA SUSTENNA vs OAAP patients had 16% fewer all-cause inpatient days (RR: 0.84; 95% CI: 0.72-0.96; P=0.004), 35% fewer long-term care days (RR: 0.65; 95% CI: 0.44-0.88]; P=0.012), and a 22% lower rate of home care visits (RR: 0.78; 95% CI: 0.58-1.00; P=0.048). Recently Diagnosed: The rate of home care services was significantly lower for INVEGA SUSTENNA vs OAAP patients (RR: 0.43; 95% CI: 0.18-0.77; P=0.008). *Healthcare Costs: Overall Cohort: INVEGA SUSTENNA patients had significantly lower medical costs compared to OAAPs (MMCD: $286; P<0.001) primarily due to lower inpatient and home care costs as noted above. This offset most of the higher pharmacy costs (MMCD: $323; P<0.001), resulting in similar total healthcare costs for both groups (MMCD: $37; P=0.709). Recently Diagnosed (aged: 18-25 yrs): In this subgroup of patients, INVEGA SUSTENNA was also associated with significantly lower medical costs compared to OAAPs (MMCD: -$466; P=0.028), driven mainly by lower home care costs as noted above. This appeared to offset higher pharmacy costs, resulting in total costs which were not significantly different from OAAP patients (MMCD=-$144; P=0.553). Conclusion:* Recently diagnosed patients with schizophrenia (aged 18-25 years) who initiated on INVEGA SUSTENNA were more likely to be adherent and persist on their index medication, and had significantly lower medical costs that offset the higher pharmacy costs, compared to those initiated on OAAPs.
Pesa et al (2017)¹⁷ conducted a retrospective cohort study assessing the impact of treatment with INVEGA SUSTENNA vs OAPs on healthcare costs and resource utilization among eligible patients with schizophrenia over a 12-month follow-up period. *Data Sources: Medi-Cal Medicaid claims database from July 1, 2008 – December 31, 2014 Sample Size* *after PSM: INVEGA SUSTENNA: n=722; OAPs: n=722 All-Cause Healthcare Utilization: A significantly lower percentage of INVEGA SUSTENNA vs OAP patients were hospitalized (61.6% vs 77.4%, respectively; P<0.001), had an ER visit (49.0% vs 56.0%, respectively; P=0.008), or had an outpatient visit (78.8% vs 89.6%, respectively; P<0.001). INVEGA SUSTENNA vs OAP patients had significantly fewer inpatient days on average (15.0 vs 27.7, respectively; P<0.001). All-Cause Healthcare Costs: While mean pharmacy costs were significantly higher for INVEGA SUSTENNA vs OAP patients ($16,347 vs $9,115, respectively; P<0.001), INVEGA SUSTENNA patients incurred significantly lower mean inpatient ($5,060 vs $10,880; P<0.001), ER ($379 vs $547; P=0.021), outpatient office ($997 vs $1,412; P=0.012) and outpatient-related costs ($2,763 vs $3,353; P=0.019), respectively. Therefore, the resulting total medical and pharmacy cost differences between the cohorts were not significantly different (INVEGA SUSTENNA: $25,546 vs OAP: $25,307; P=0.853). Subset Analysis: In a subset of patients recently hospitalized or nonadherent to antipsychotic therapy, INVEGA SUSTENNA was associated with a significantly higher PDC, fewer hospitalizations and lower inpatient costs compared to OAPs. Similar to the main analysis, lower inpatient costs offset increased pharmacy costs resulting in no significant total cost differences between cohorts. The authors note that prescription costs did not account for any negotiated rebates or discounts therefore, the net effect is unknown (Pesa et al, 2016⁴⁰). Conclusion:* In patients with schizophrenia enrolled in California Medicaid, initiation of INVEGA SUSTENNA was associated with significantly fewer inpatient hospitalizations and ER visits, lower inpatient and ER costs, and improved treatment continuity compared to OAPs.
Young-Xu et al (2016)⁷ conducted a retrospective, longitudinal cohort design comparing treatment patterns, HRU and costs in Veterans treated with INVEGA SUSTENNA vs OAAPs for schizophrenia over a 12-month follow-up period. IPTW was utilized to adjust for baseline differences between INVEGA SUSTENNA and OAAPs. *Data Sources:* Electronic medical record data from the Veterans Health Administration from January 1, 2010 – October 31, 2014 *Sample Size after IPTW: INVEGA SUSTENNA: n=5,052; OAAPs (aripiprazole; asenapine maleate; iloperidone; lurasidone; olanzapine; quetiapine fumarate; risperidone; ziprasidone; paliperidone): n=5,238 Treatment Patterns: INVEGA SUSTENNA initiators stayed on treatment for a longer duration of time compared to patients initiating OAAPs (209.6 vs 165.0 days, respectively; P<0.001). HRU: A significantly lower rate of inpatient stays (IRR: 0.89; 95% CI: 0.87-0.91; P<0.001) and days in an inpatient setting (IRR: 0.82; 95% CI: 0.82-0.83; P<0.001) were observed for INVEGA SUSTENNA vs OAAP initiators. A 3% increase in the rate of outpatient visits per patient during INVEGA SUSTENNA treatment was most likely driven by the higher frequency of Mental Health Intensive Case Management (MHICM) visits compared to OAAP (IRR: 1.03; 95% CI: 1.02-1.03; P<0.001); MHICM IRR: 1.81; 95% CI: 1.79- 1.82; P<0.001). Costs: The total overall-cause cost difference of initiating treatment with INVEGA SUSTENNA vs OAAPs was -$8,511.36 (95% CI: -$14,999.07 to -$2,052.16; P=0.012). Greater mean outpatient visit costs and pharmacy costs associated with INVEGA SUSTENNA were offset by lower all-cause inpatient stay costs resulting in cost savings associated with INVEGA SUSTENNA vs OAAPs. Socioeconomic Outcomes: Patients treated with INVEGA SUSTENNA vs OAAPs were 20% more likely to increase their income (95% CI: 1.02-1.41; OR: 1.20; P=0.027) and 18% less likely to become homeless (95% CI: 0.75-0.89; OR: 0.82; P<0.001). Sensitivity Analysis: A sensitivity analysis looked at patients stratified according to participation in MHICM at baseline. Total overall-cost difference of INVEGA SUSTENNA vs OAAPs among MHICM participants at baseline was -$22,584 (P<0.001), while the difference in total cost among non-participants was not significant. MHICM participation during the observation period may have impacted the results of this study because a greater number of MHICM visits were observed among INVEGA SUSTENNA patients in both baseline MHICM stratified groups (ie, patients participating in MHICM visits at baseline and patients not participating in MHICM visits at baseline). Conclusion:* Veterans with schizophrenia initiated on INVEGA SUSTENNA experienced lower rates of inpatient HRU, lower total healthcare costs, increased income and lower likelihood of homelessness, compared to those initiated on OAAPs.
Lafeuille et al (2015)⁸ conducted a retrospective cohort analysis to describe utilization patterns and institutional costs of inpatients who were prescribed INVEGA SUSTENNA or OAAPs. IPTW based on the propensity score was used to create the matched cohort between INVEGA SUSTENNA and OAAPs. *Data Sources: Premier Perspective Comparative Hospital Database with data from more than 600 acute care hospitals across the US from January 2009 – March 2012 Sample Size after IPTW:* INVEGA SUSTENNA: n=19,526; OAAP: n=26,099 *Rehospitalizations and ER visits: The risk of any all-cause ER visit and/or rehospitalization was significantly lower in the INVEGA SUSTENNA cohort than in the OAAP cohort. Hazard ratio for INVEGA SUSTENNA vs OAAPs, all patients: All-cause rehospitalizations: 0.64 (95% CI: 0.62-0.67; P<0.0001) All-cause ER visits: 0.53 (95% CI: 0.51-0.55; P<0.0001) All-cause rehospitalizations and ER visits combined: 0.61 (95% CI: 0.59-0.63; P<0.0001) Institutional Costs: Up to 6 months after index hospitalization discharge, the mean adjusted cost difference for rehospitalizations, ER and hospital outpatient visits was -$404 per-patient-per-month (PPPM) for the INVEGA SUSTENNA cohort relative to the OAAP cohort (P<0.0001). The mean adjusted all-cause cost difference at 12 months after index hospitalization discharge was lower for the INVEGA SUSTENNA cohort relative to the OAAP cohort (-$212 PPPM; however, the results were not statistically significant [P=0.2164]). Sensitivity Analysis: When the analysis was restricted to patients with a propensity score within the common-support region (range of the score values overlapping between the INVEGA SUSTENNA and OAAP cohorts), similar results were observed. The mean adjusted cost difference, based on a sensitivity analysis including only patients who had a propensity scores within the range of propensity score overlap for the two cohorts (common support range), was lower for INVEGA SUSTENNA vs OAAP cohort; however, the results were not significant (first 6 months after discharge: -$199 PPPM, P=0.1202; first 12 months after discharge: -$71 PPPM, P=0.6613). Conclusion:* In a large hospital database, patients with schizophrenia who received INVEGA SUSTENNA had lower rates of ER visits, rehospitalizations and institutional costs compared to those who received OAAPs.
Marcus et al (2015)⁹ conducted a retrospective cohort study examining adherence and rehospitalization in nonadherent Medicaid patients receiving OAP vs LAIs in the 6 months following a schizophrenia-related hospitalization. *Data Sources:* Truven Health Analytics MarketScan Medicaid research claims database from January 1, 2010 – July 31, 2013 *Sample size: LAIs (fluphenazine decanoate; haloperidol decanoate; RLAI; INVEGA SUSTENNA): n=340; OAP: n=3,428 Adherence: Compared to patients receiving OAPs, LAI users had lower odds of being nonadherent (AOR: 0.35; 95% CI: 0.27-0.46; P<0.001) and having a continuous gap ≥60 days (AOR: 0.45; 95% CI: 0.34-0.60; P<0.001) FGA and SGA LAI users had lower odds of nonadherence and lower odds of a continuous gap ≥60-days compared to OAP users. Following sensitivity analyses, similar results were observed with continuous gaps of ≥30 and ≥90 days. Rehospitalization: LAI users had significantly lower odds of a schizophrenia-related rehospitalization (AOR: 0.73; 95% CI: 0.54-0.99; P=0.041) compared to OAP users; however, when assessed separately, only SGA (AOR: 0.59; 95% CI: 0.38-0.90; P=0.015) and not FGA (AOR: 0.90; 95% CI: 0.60-1.34; P=0.599) LAI users had a significant reduction. Among the individual LAIs, only INVEGA SUSTENNA users had significantly lower odds of rehospitalization (AOR: 0.53; 95%CI: 0.30-0.94; P=0.031) compared to OAP users while the odds of rehospitalization was numerically lower but not statistically significant for RLAI, fluphenazine decanoate and haloperidol decanoate users. Following sensitivity analyses, similar results were observed with mental health-related and all-cause hospitalizations. Conclusion:* Nonadherent Medicaid patients initiated on LAI antipsychotics had lower odds of nonadherence, discontinuation, and rehospitalization compared to those initiated on OAPs.
Pesa et al (2015)¹⁵ conducted a retrospective study assessing the impact of treatment with INVEGA SUSTENNA vs OAAP on healthcare costs and resource utilization over a 12-month follow-up period among eligible patients with schizophrenia. *Data Sources:* Truven Health MarketScan^® Multi-State Medicaid Database (2009-2011) *Sample Size: INVEGA SUSTENNA initiators: n=984; OAAP initiators (aripiprazole; asenapine; iloperidone; lurasidone; olanzapine; paliperidone; quetiapine; risperidone; ziprasidone): n=4199 Cost Outcomes: All-cause prescription costs were $1004 (95% CI: $986 - $1,021; P<0.0001) higher per patient-month with INVEGA SUSTENNA utilization vs without INVEGA SUSTENNA utilization. INVEGA SUSTENNA was associated with significant reductions in all-cause inpatient (-$234, 95% CI: -$362 to -$107; P<0.0003) and outpatient (-$336, 95% CI: -$382 to -$290; P<0.0001) service costs, thus reducing the overall estimated monthly cost differential associated with INVEGA SUSTENNA to $434 (95% CI: $298 - $569; P<0.0001). Utilization Outcomes: (adjusted per-month, per-patient utilization risk ratios associated with INVEGA SUSTENNA utilization over 12 months post-index) All-cause hospitalizations: 0.6441 (95% CI: 0.5954-0.6967; P<0.0001) All-cause ER visits: 0.8228 (95% CI: 0.7892-0.8468; P=0.0134) Conclusion:* Medicaid patients treated with INVEGA SUSTENNA had significantly lower inpatient admissions, inpatient costs, and outpatient costs which partially offset higher drug acquisition costs, compared to those treated with OAAPs.
Schizoaffective Disorder
Xiao et al (2016)¹³ conducted a retrospective longitudinal cohort study assessing the impact of treatment with INVEGA SUSTENNA vs OAAPs on healthcare resource utilization and costs among eligible patients with schizoaffective disorder. *Data Sources:* Medicaid databases from Florida, Iowa, Kansas, Mississippi, Missouri and New Jersey from January 1, 2010 – December 31, 2013 *Unadjusted Sample Sizes: INVEGA SUSTENNA: n=876; OAAPs (aripiprazole; asenapine maleate; iloperidone; lurasidone; olanzapine; paliperidone; quetiapine fumarate; risperidone; ziprasidone): n=10,778 Sample Sizes after IPTW and PSM:* PSM Dataset: N=846 for both cohorts; IPTW Dataset: N=5,589 for INVEGA SUSTENNA and 6,065 for OAAPs. *Healthcare Costs: (costs were based on amounts paid by state Medicaid programs, without supplemental rebates, and adjusted to 2013 US dollars according to the Consumer Price Index, medical care component) A lower all-cause medical cost was associated with patients initiating INVEGA SUSTENNA vs OAAPs ([MMCD] PSM: -$382.56; P=0.0001; IPTW: -403.01; P=0.0160). This was attributable to lower inpatient, ER and home care service costs associated with INVEGA SUSTENNA. Higher all-cause pharmacy costs ([MMCD] PSM: $269.79; P<0.0001; IPTW: 350.40; P<0.0001) were observed among patients initiating INVEGA SUSTENNA vs OAAPs. Overall, all-cause total pharmacy and medical costs were similar between the treatment cohorts (lower medical costs offset the higher pharmacy costs for INVEGA SUSTENNA patients; [MMCD] PSM: -$112.77; P=0.4144; IPTW: -52.61; P=0.6967). Similar findings were obtained (PSM and IPTW) for mental-related healthcare costs. HRU: Patients initiating INVEGA SUSTENNA, vs OAAPs, had less frequent and shorter inpatients visits, fewer ER visits and received less homecare. Most incidence rate ratios were significant with the IPTW compared to PSM approach (P<0.0001) most likely because the IPTW pseudo-population retained all patients thereby increasing statistical power. Risk of Hospital Readmission Among Patients with at Least One Follow-Up Hospitalization: Compared to OAAPs, patients receiving INVEGA SUSTENNA had a lower risk of hospital readmission (OR within 30, 60 and 90 days were 0.89, 0.82 and 0.80, respectively; P<0.05 for all comparisons) in this subset of patients. Conclusion:* Medicaid patients with schizoaffective disorder who were treated with INVEGA SUSTENNA had fewer and shorter inpatient visits, which resulted in significantly lower medical costs that offset the higher pharmacy costs, compared to those treated with OAAPs.
Pesa et al (2015)¹² conducted a retrospective database analysis that compared utilization and costs associated with INVEGA SUSTENNA and OAAPs (aripiprazole, asenapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone) in Medicaid and commercially insured schizoaffective disorder populations. Weighting and multivariate analyses were carried out using marginal structural models to control for baseline and time-varying confounding factors. *Data Sources: Truven Health MarketScan^® Multi-State Medicaid Database and Commercial Claims and Encounters Database (2009-2012) Sample Size: Medicaid Database: INVEGA SUSTENNA initiators: n=1,320; OAAP initiators: n=4,216 Commercial Claims and Encounters Database: INVEGA SUSTENNA initiators: n=167; OAAP initiators: n=2,044 Medicaid Patients: Utilization Outcomes: In the patient-months with INVEGA SUSTENNA administration the risk of all-cause hospitalization, all-cause ER, and mental health–related hospitalization was significantly reduced. Adjusted risk of inpatient admission: INVEGA SUSTENNA, 18% vs no-INVEGA SUSTENNA, 30% (25% difference; P<0.0001) Adjusted risk of ER visit: INVEGA SUSTENNA,13% vs no-INVEGA SUSTENNA,17% (11% difference; P=0.0203) Adjusted risk of mental health-related admission: INVEGA SUSTENNA, 14% vs no-INVEGA SUSTENNA, 24% (28% difference; P=0.0002) Cost Outcomes: The monthly cost differential associated with INVEGA SUSTENNA vs OAAPs was reduced to $722 (95% CI, $526 to $917) due to lower inpatient (-$185; 95% CI, -$40 to -$331) and outpatient (-$229; 95% CI, -$69 to -$389) costs in the months with INVEGA SUSTENNA that partially offset higher drug costs ($1,136; 95% CI, $1,063 to $1,209). Commercial Patients: Utilization Outcomes: Compared to Medicaid patients, commercial patients showed similar inpatient utilization patterns. Cost Outcomes: Compared to Medicaid patients, similar inpatient, pharmacy and all-cause outpatient cost patterns were observed by commercial patients. Conclusion:* In Medicaid and commercially insured patients with schizoaffective disorder, treatment with INVEGA SUSTENNA was associated with significantly lower inpatient admissions and lower inpatient and outpatient costs compared with OAAPs, which partially offset the higher drug acquisition costs.
Abbreviations: AOR, adjusted odds ratio; CI, confidence interval; ED, emergency department; ER, emergency room; FGA, first generation antipsychotic; HRU, healthcare resource utilization; IPTW, inverse probability of treatment weights; IQR, interquartile range; IRR, incidence rate ratio; LAI, long-acting injectable; MMCD, mean monthly cost difference; OAP, oral antipsychotic; OAAP, oral atypical antipsychotic; OR, odds ratio; PDC, proportion of days covered; PPPM, per-patient-per-month; PSM, propensity score matching; PY, patient year; RR, rate ratio; SD, standard deviation; SGA, second generation antipsychotic.

Single-arm “Real-World” Utilization

Single-arm studies evaluating the “real-world” utilization of INVEGA SUSTENNA have been conducted. Results are summarized in the Table: Single-arm “Real-World” Utilization Health Outcomes Results.

Single-arm “Real-World” Utilization Health Outcomes Results

Zhdanava et al (2021)²⁶ conducted a retrospective observational study to analyze medication adherence, HRU, and costs during 12-month post- vs pre-INVEGA SUSTENNA among Medicaid beneficiaries with schizophrenia and a schizophrenia relapse before transitioning to INVEGA SUSTENNA. *Data Sources:* Medicaid data from Iowa (Q1 2009 to Q3 2016), Kansas (Q1 2009 to Q1 2018), Mississippi (Q1 2009 to Q1 2018), Missouri (Q1 2009 to Q1 2018), New Jersey (Q1 2009 to Q1 2014), and Wisconsin (Q1 2009 to Q4 2013) Sample size: n=1,725 *Treatment Patterns:* Among patients with ≥1 prior relapse, mean (SD) PDC for antipsychotic therapy increased from 0.49 (0.30) to 0.60 (0.31), and the likelihood of adherence (PDC ≥80%) increased by 93% (all P<0.01) from the pre- to post-INVEGA SUSTENNA periods. At 6 and 12 months, 51.1% and 28.8% patients, respectively, were persistent to treatment with INVEGA SUSTENNA. *HRU:* The likelihood of all-cause inpatient admission decreased by 89%, and the total number of days spent in an inpatient setting decreased by 31% (P<0.01) from pre- to post-INVEGA SUSTENNA periods. All-cause ER visits decreased by 49% (P<0.01) post INVEGA SUSTENNA. These decreases were more substantial as the number of relapses at baseline increased. *Healthcare cost: All-causes total health care costs were similar in patients with >1 relapse pre- vs post-INVEGA SUSTENNA (cost difference: $123 per patient per month [PPPM]; P=0.10). Total allcause health care costs were significantly lower PPPM in patients with ≥2, ≥3, and ≥4 (-$209, P=0.04; -$467, P<0.01; -$685, P<0.01) prior relapses. Conclusion:* In Medicaid patients with schizophrenia and prior schizophrenia relapse, initiation of INVEGA SUSTENNA was associated with improvement in medication adherence to antipsychotics, and reduction in inpatient and ER services.
Mahabaleshwarkar et al (2021)²⁷ conducted a retrospective cohort study comparing healthcare resource utilization during 12-month pre- and post- initiation of INVEGA SUSTENNA. *Data Source:* Atrium Health’s electronic medical records from 01/2008 to 04/2020 *Sample size:* n=210 *HRU:* From pre- to post-index periods, initiation of INVEGA SUSTENNA was associated with a significant decrease in all-cause patient visits (67.6% vs 22.4%; P<0.001), 7-day readmissions (5.2% vs 1.0%; P=0.013), 30-day readmissions (12.4% vs 2.4%; P<0.001), and ER visits (68.6% vs 45.7%; P<0.001). A significant reduction from pre- to post-index was observed in mean number of inpatient visits (1.2 vs 0.4, P<0.001), 7-day readmissions (0.1 vs 0.0; P=0.02), 30-day readmissions (0.2 vs 0.1; P=0.002), and ER visits (2.3 vs 1.2; P<0.001), and length of stay (14.2 vs 4.4; P<0.001) *Subgroup analysis:* In a subgroup analysis of patients with ≥1 relapse at baseline (n=157), the patterns in changes of HRU from pre- to post-index were similar to the overall cohort, with the extent of change being slightly higher. *Conclusion:* In patients with schizophrenia treated in a large integrated healthcare system, initiation of INVEGA SUSTENNA was associated with reduced inpatient and ER utilization, with a more substantial reduction observed in a subgroup of patients with prior relapse.
Patel et al (2020)³¹ conducted a retrospective cohort study comparing the treatment patterns, HRU, and costs during 6-month or 12-month before and after switching from oral RIS/PALI to INVEGA SUSTENNA. *Data Source:* Veterans’ Health Administration (VHA) database from 01/2014 – 03/2018 *Sample Size:* 6-month cohort: n=676; 12-month cohort: n=493 *Treatment Pattern:* Adherence (PDC and MPR ≥80%, respectively) to oral RIS/PALI during the 6 months pre-INVEGA SUSTENNA was 16.4% and 25.7%. During the 6 months post-INVEGA SUSTENNA, adherence to INVEGA SUSTENNA was 39.5% and 49.6%, respectively. Adherence to oral RIS/PALI during the 12 months pre-INVEGA SUSTENNA was 11.0% and 22.1% (PDC and MPR ≥80%, respectively). During the 12 months post-INVEGA SUSTENNA, adherence to INVEGA SUSTENNA was 27.0% and 35.9%, respectively. *HRU:* From 12 months pre- to post-switch, significant reductions were observed in the number of all-cause inpatient hospital stays (2.3 vs 1.0; P<0.05) and all-cause inpatient length of stay (28.1 vs 14.0 days; P<0.05), while an increase in total number of all-cause outpatient visits (47.6 vs 54.6; P<0.05) and number of all-cause outpatient pharmacy visits (26.0 vs 33.0; P<0.05) were observed. A similar trend was observed in the 6 months cohort. *Healthcare Cost:* All-cause total medical costs decreased significantly ($63,871 to $49,558; P<0.05) from 12 months pre to post-switch, largely driven by decreases in all-cause inpatient stay costs ($41,886 vs $20,489; P<0.05). However, a significant increase in all-cause pharmacy cost ($3,109 to $12,112; P<0.05) was observed during the 12 months post-switch period. Overall, no significant change was seen in all-cause total cost from pre to post-switch. A similar trend was observed for the 6 months cohort. *Conclusion:* In veterans with schizophrenia, switching from oral RIS/PALI to INVEGA SUSTENNA improved adherence while decreasing the utilization of inpatient services.
Patel et al (2020)³⁰ conducted a retrospective observational cohort comparing physical and psychiatric comorbidity-related outcomes, adherence, HRU, and costs during 6-month pre- and post-transition to INVEGA SUSTENNA from oral risperidone/paliperidone in patients with schizophrenia. *Data Source:* IQVIA™ PharMetrics Plus database from 01/01/2012–07/31/2018 *Sample Size:* n=427 *Adherence:* Mean PDC was higher post-transition vs pre-transition (mean: 0.81 vs 0.68; mean difference: 0.13; P<0.001). The proportion of patients with a PDC ≥80% significantly increased from 45.0% to 68.1% following INVEGA SUSTENNA transition (OR: 2.62; P<0.001). *HRU:* After transitioning to INVEGA SUSTENNA, patients were less likely to have an all-cause ER visit (OR: 0.51, P<0.001) or inpatient stay (OR: 0.39, P<0.001). Patients also had a decrease in ER visits, inpatient stays, and days spent inpatient per month (P<0.001 for all). *Healthcare Costs:* All-cause total healthcare costs remained similar post- vs pre-transition to INVEGA SUSTENNA (mean monthly cost difference [MMCD]: $228; P=0.260). All-cause pharmacy costs increased post-INVEGA SUSTENNA (MMCD: $960; P<0.001); however, costs were offset by decreased all-cause medical costs (MMCD: -$732; P<0.001). Medical costs reduction was driven by lower costs related to reduction in inpatient stays (MMCD: -$695; P<0.001) and ER visits (MMCD: -$63; P<0.001). *Subgroup analysis:* In a subgroup analysis of patients with ≥1 all-cause inpatient stays during the 6-month pre-transition period (n=177), the changes in patterns in adherence were similar to the overall cohort. All-cause total healthcare costs were significantly lower following transition to INVEGA SUSTENNA (MMCD: -$1,308; P<0.001). Reduction in all-cause medical costs (MMCD: -$2,251; P<0.001) was largely driven by lower inpatient costs (MMCD: -$2,182; P<0.001), followed by lower ER visit costs (MMCD: -$133; P<0.001), which offset the increase in all-cause pharmacy costs (MMCD: $943; P<0.001). *Conclusion:* Transition to INVEGA SUSTENNA from oral RIS/PALI was associated with an improvement in medication adherence in patients with schizophrenia across insurance types. Significant reduction in HRU and total healthcare costs were observed in those with ≥1 hospitalization before switching.
Bhatta et al (2019)³² conducted a retrospective cohort study assessing the impact of LAIs on risk of reincarcerations in patients with schizophrenia or schizoaffective disorder and a history of prior incarceration. *Data Sources:* Clinical data from a community-based service provider from January 2010 – June 2016 *Sample Size:* ≥1 arrest 1-year prior index: n=132; ≥1 arrest 2 years prior index: n=196 *Reincarcerations:* A significant reduction in the incidence of ≥1 arrest was observed among patients with schizophrenia or schizoaffective disorder and history of encounters with the criminal justice system during a 2-year follow-up period after initiation of LAI treatment, specifically INVEGA SUSTENNA, at a community mental health center. Post-LAI initiation incidence of arrest declined significantly from 100.0% to 34.8% (P<0.001) and 44.9% (P<0.001) during the 1- and 2-year follow-up periods, respectively. Among those on INVEGA SUSTENNA, the incidence of arrest declined from 100.0% to 33.0% (P<0.01) and 42.5% (P<0.01) 1 and 2 years after LAI initiation, respectively. Conclusion: INVEGA SUSTENNA initiation was associated with a significant reduction in the incidence of reincarceration among patients with schizophrenia or schizoaffective disorder and a history of encounters with the CJS.
El Khoury et al (2019)²⁵ conducted a retrospective cohort study comparing the treatment patterns, HRU, and costs during the 12 months pre- and post-transition to INVEGA SUSTENNA from oral risperidone or paliperidone in US veterans diagnosed with schizophrenia who had ≥1 prior hospitalization. *Data Sources:* Health claims from the Veterans Health Administration (VHA) database from January 2014 – March 2018 *Sample Size: INVEGA SUSTENNA: n=319 Treatment Patterns: During pre-INVEGA SUSTENNA transition, 7.2% (PDC ≥ 80% of the veterans were adherent to oral risperidone or paliperidone. Post-INVEGA SUSTENNA transition, 27.6% were adherent to INVEGA SUSTENNA. The mean PDC increased from 0.3 to 0.5 from pre- to post-INVEGA SUSTENNA transition. HRU:* Veterans with prior hospitalization had longer all-cause inpatient lengths of stay during the pre-INVEGA SUSTENNA period (43.4 vs 18.3 days; P<0.0001), more all-cause inpatient stays (3.5 vs 1.4; P<0.0001),fewer outpatient visits (48.9 vs 58.1; P<0.0001), and fewer pharmacy visits (25.8 vs 33.6; P<0.0001) compared with the post-INVEGA SUSTENNA period. *All-cause Healthcare Costs:* Overall, a significant decline was observed in all-cause total costs ($91,181 vs $69,106; P<0.0001) from pre- to post-INVEGA SUSTENNA transition. All-cause total medical costs decreased significantly among veterans ($87,917 vs $56,947; P<0.0001) from pre- to post-INVEGA SUSTENNA transition, largely driven by a decrease in all-cause inpatient visit costs ($64,702 vs $26,147; P<0.0001). However, a significant increase was observed in all-cause pharmacy ($3,263 vs $12,159; P<0.0001) and outpatient costs ($23,215 vs $30,800; P<0.0001) during post-NVEGA SUSTENNA transition. *Conclusion:* Veterans with schizophrenia and prior hospitalization had significantly lower all-cause total medical and total healthcare costs, driven by a decrease in all-cause inpatient healthcare utilization and costs, after transitioning to INVEGA SUSTENNA from oral RIS/PALI.
Abbreviations: CJS, criminal justice system; CRIS, Clinical Record Interactive Search; ER, emergency room; HCP, healthcare provider; HRU, healthcare resource utilization; LAI, long-acting injectable; NHS, National Health Service; PALI, paliperidone; PPPM, per patient per month; RIS, risperidone; RR, rate ratio; SD, standard deviation; SLAM, South London and Maudsley NHS Foundation Trust.

US Healthcare Resource Utilization, Cost Outcomes, and Treatment Patterns – INVEGA SUSTENNA vs Oral Antipsychotics in Patients With Comorbidities

Studies assessing utilization outcomes and institutional costs following treatment with INVEGA SUSTENNA vs oral antipsychotics have been conducted in patients with comorbidities treated for schizophrenia. Outcomes of these studies, focused on all-cause results, are summarized in the Table: US Healthcare Resource Utilization, Cost Outcomes, and Treatment Patterns – INVEGA SUSTENNA vs Oral Antipsychotics in Patients With Comorbidities.

US Healthcare Resource Utilization, Cost Outcomes, and Treatment Patterns – INVEGA SUSTENNA vs Oral Antipsychotics in Patients With Comorbidities

Cardiometabolic Comorbidities
Lafeuille et al (2018)²⁰ conducted a retrospective cohort study to compare adherence, healthcare costs and HRU in patients with schizophrenia and cardiometabolic comorbidities (CMC; i.e. diabetes or CVD) initiated on either INVEGA SUSTENNA or an OAAP over a 12 month follow-up period. Multivariate adjustment was conducted for cost and HRU outcomes. *Data Sources:* Medicaid claims databases in Iowa, Kansas, Mississippi, Missouri, New Jersey, and Wisconsin (July 2009 – March 2015) *Sample size:* INVEGA SUSTENNA: n=371; OAAP: n=8,296 *Adherence:* Adherence was defined as not having any gap greater than 30, 60, or 90 days between days with available medication during the 12 months following treatment initiation. INVEGA SUSTENNA compared to OAAP was associated with greater adherence to index treatment when no gap ≥ 60 days (34% vs 27%, respectively; P=0.001) or no gap ≥90 days (40% vs 33%, respectively; P=0.006). *Healthcare costs:* Expressed as adjusted MMCD. Cost analyses were represented in 2015 US Dollars before rebates. Compared to patients receiving OAAP, adjusted all-cause medical costs were significantly lower for INVEGA SUSTENNA patients (MMCD: -$369; P<0.004) while all-cause pharmacy costs were significantly higher (MMCD: $279; P<0.001) resulting in no significant total cost differences (MMCD -$90, P=0.357). Significant medical cost savings for INVEGA SUSTENNA were mainly driven by lower costs associated with inpatient visits (MMCD: -$167; P=0.028), skilled nursing and long-term care admissions (MMCD: -$86, P=0.008), and home care (MMCD: -$145; P<0.001). *HRU:* INVEGA SUSTENNA vs OAAPs were associated with significantly lower rates of all-cause skilled nursing and long-term care admissions (aIRR=0.57; P=0.004) and all-cause home care services (aIRR=0.71; P=0.032) with significantly higher 1-day mental institution visits (aIRR=1.19; P<0.001). INVEGA SUSTENNA vs OAAP patients also had fewer CMC-related inpatient admissions (aIRR=0.73; P<0.001) with shorter length of stays (aIRR=0.72; P=0.020) and fewer CMC-related skilled nursing and long-term care admissions (aIRR=0.56; P=0.016). *Conclusion:* Medicaid patients with schizophrenia and cardiometabolic comorbidities who were initiated on INVEGA SUSTENNA had lower utilization of cardiometabolic comorbidity-related inpatient and long-term care services, and similar total healthcare costs, compared with OAAPs.
Kamstra et al (2018)²⁹ conducted a retrospective longitudinal cohort study to compare adherence and Medicaid spending over a 12-month follow-up period in patients with schizophrenia and CVD, diabetes, HTN, or obesity initiated on either INVEGA SUSTENNA or an OAAP. *Data Sources:* Medicaid claims data from Iowa, Kansas, Mississippi, Missouri, and New Jersey (September 2008 to March 2015 for all states except New Jersey which had available data until March 2014). IPTW was utilized to balance baseline demographics and compare outcomes between INVEGA SUSTENNA and OAAPs. Weights were calculated based on PS which were estimated using multivariate logistic regression adjusted for baseline characteristics. *Sample Size after IPTW: CVD group (INVEGA SUSTENNA: n=2,054; OAAP: n=2,247); Diabetes group (INVEGA SUSTENNA: n=2,863; OAAP: n=2,906); HTN group (INVEGA SUSTENNA: n=4,699; OAAP: n=4,930) Obesity group: INVEGA SUSTENNA: n=1,223; OAAP: n=1,290 Adherence (PDC ≥80%): PDC was defined as the sum of nonoverlapping days of supply of index medication divided by a fixed period of time (365 days). Compared to OAAPs, adherence was significantly more likely in INVEGA SUSTENNA patients with CVD (22.1% vs 28.6%, respectively) or obesity (21.9% vs 32.9%, respectively), similar for HTN patients (23.5% vs 24.6%, respectively), and significantly less likely for diabetes patients (24.4% vs 22.0%, respectively). Persistence (no gap ≥60 days): Persistence was defined as having no continuous gap ≥60 days between the days of supply of the index medication refills. Across all comorbidities, INVEGA SUSTENNA patients were more likely to be persistent to the index antipsychotic compared to patients receiving OAAPs. Healthcare costs: Expressed as adjusted MMCD. Cost analyses were represented in 2015 inflated US Dollars. Lower medical costs fully offset higher pre-rebate pharmacy costs in INVEGA SUSTENNA patients with diabetes, HTN, or obesity. Across all comorbidities, there was no significant difference in total costs between INVEGA SUSTENNA and OAAP patients. Conclusion:* Medicaid patients with schizophrenia and CVD, diabetes, HTN or obesity who initiated on INVEGA SUSTENNA had lower all-cause medical costs compared to those initiated on OAAPs. Adherence was higher in patients with schizophrenia who initiated on INVEGA SUSTENNA in the CVD, HTN, and obesity groups, and persistence demonstrated higher rates across all 4 comorbidities compared to those initiated on OAAPs.
Substance-Related Disorders
Joshi et al (2018)²¹ conducted a retrospective cohort study to compare treatment patterns, Medicaid spending, and HRU over a 12-month follow-up period in schizophrenia patients with substance-related disorders initiated on INVEGA SUSTENNA or an OAAP. Multivariate adjustment was made for cost and HRU outcome measures. *Data Sources:* Medicaid claims databases in Iowa, Kansas, Mississippi, Missouri, New Jersey, and Wisconsin (July 2009 – March 2015) *Sample size: INVEGA SUSTENNA: n=351; OAAP: n=4,869 Adherence: (PDC≥80%) Compared to OAAPs, a higher proportion of INVEGA SUSTENNA patients were adherent on the index AP (18% vs 29%, respectively; P<0.001) or any AP (31% vs 39%, respectively; P<0.001) at 12 months post-index. Persistence: (no continuous gap in days of medication supply ≥90 days) At 12 months, INVEGA SUSTENNA patients were more likely than OAAP patients to be persistent on the index AP (47% vs 32%. respectively; P<0.001) or any AP (60% vs 50%, respectively; P<0.001). Healthcare costs: INVEGA SUSTENNA vs OAAP patients had lower medical costs (MMCD=-$191; P=0.020) but higher pharmacy pre-rebate costs (MMCD: $250; P<0.001), resulting in no significant difference in total healthcare costs (MMCD: $59; P=0.517). Significantly lower inpatient costs (MMCD:-$152; P=0.016) and home care costs (MMCD:-$42; P=0.016) appeared to drive medical cost savings. INVEGA SUSTENNA patients also had lower ER costs (MMCD: -$12; P=0.008). HRU: INVEGA SUSTENNA vs OAAP patients had significantly lower rates of outpatient visits (IRR: 0.90; P=0.036) and inpatient days (IRR: 0.72; P=0.016) but higher rates of mental health institute days (IRR: 1.34; P<0.001) and 1-day mental health institute admissions (IRR: 1.17; P<0.001). Conclusion:* Medicaid patients with schizophrenia and substance-related disorders who initiated on INVEGA SUSTENNA were more likely to be adherent and persistent to the index antipsychotic or any antipsychotic and had lower medical costs which fully offset higher pre-rebate pharmacy costs, compared to OAAPs.
Lefebvre et al (2017)²² conducted a retrospective longitudinal cohort study comparing adherence, HRU and costs over a 12-month follow-up period among veterans with schizophrenia and comorbid substance abuse treated with INVEGA SUSTENNA vs OAAP. All analyses were conducted in the IPTW-weighted cohort which adjusted for baseline characteristics. *Data Sources:* Healthcare claims from the Veterans Health Administration (Northeast; Midwest; South; West; other) from January 1, 2010 – June 30, 2015. *Sample size after IPTW: INVEGA SUSTENNA: n=3,387; OAAP (aripiprazole; asenapine maleate; iloperidone; lurasidone; olanzapine; paliperidone; quetiapine fumarate; risperidone; and ziprasidone): n=3,485 Adherence:* Compared to OAAPs, INVEGA SUSTENNA was associated with a greater proportion of days covered (PDC ≥80%: 20% vs 37%, respectively; P<0.001) and a longer mean duration of treatment (158.1 vs 210, respectively; P<0.001). In addition, INVEGA SUSTENNA was less likely to have 30-day or 60-day discontinuation compared to OAAPs (69.9% vs 85% and 60.2% vs 75.9%, respectively; P<0.001 for both). *HRU: INVEGA SUSTENNA vs OAAPs was associated with a decrease in all-cause and substance abuse-related inpatient visits (aIRR: 0.88 and 0.80, respectively; P<0.001, both), mental health inpatient stays (aIRR: 0.88 and 0.85, respectively; P<0.001, both), and long-term care stays (aIRR: 0.53 and 0.22, respectively; P<0.001) but was associated with an increase in the rate of mental health-intensive case management visits (aIRR: 1.51 and 1.72, respectively; P<0.001). Healthcare costs: Costs were inflated to $2014 using the Medical Services component of the Consumer Price Index. INVEGA SUSTENNA had significantly reduced total medical costs compared to OAAPs (MMCD: -$10,472.56; P<0.001) Similarly, INVEGA SUSTENNA had significantly reduced substance abuse-related total medical costs compared to OAAPs (MMCD: -$8,457.39; P<0.001). Conclusion:* Veterans with schizophrenia and co-occurring substance abuse initiated on INVEGA SUSTENNA showed greater adherence and had lower medical costs as a result of fewer hospitalizations and lower rates of substance abuse-related HRU, compared to those initiated on OAAPs.
Abbreviations: aIRR, adjusted incidence rate ratio; CVD, cardiovascular disease; ER, emergency room; HRU, healthcare resource utilization; HTN, hypertension; IPTW, inverse probability of treatment weights; MMCD, mean monthly cost difference; OAAP, oral atypical antipsychotic; PDC, proportion of days covered.

Cost-Effectiveness Analysis

Pharmacoeconomic outcomes, including hospitalizations, clinical event outcomes and cost-effectiveness, were assessed from post hoc clinical trial data.¹¹^,⁴¹^,⁴² Results from Muser et al (2015) are summarized in the Table: Cost-Effectiveness Analysis.

Cost-Effectiveness Analysis

Muser et al (2015)¹¹ conducted a cost-effectiveness analysis of INVEGA SUSTENNA vs OAPs within the Paliperidone Palmitate Research In Demonstrating Effectiveness (PRIDE) trial.⁴³ *Sample Size: INVEGA SUSTENNA: n=198; OAPs: n=193 Costs: Effectiveness and costs were adjusted to 456 days (trial duration). Incremental cost-effectiveness was calculated as the adjusted cost difference divided by the adjusted effectiveness difference. Overall and component cost adjusted to 456 days are as follows: Total costs* ($8063 greater INVEGA SUSTENNA vs OAPs): INVEGA SUSTENNA: $40,923; OAPs: $32,860 Drug costs ($10,759 greater INVEGA SUSTENNA vs OAPs): INVEGA SUSTENNA: $18,592; OAPs: $7833 Total non-drug costs ($2696 lower INVEGA SUSTENNA vs OAPs): INVEGA SUSTENNA: $22,331; OAPs: $25,027 Lower non-drug costs for INVEGA SUSTENNA vs OAPs offset 25% of the greater drug cost for INVEGA SUSTENNA patients *Effectiveness: Effectiveness measures, adjusted to 456 days showed a lower number of CJS or psychiatric hospitalization events in patients receiving INVEGA SUSTENNA vs OAPs. Adjusted mean number of CJS or psychiatric hospitalization events combined: INVEGA SUSTENNA: 1.02; OAPs: 1.48 Incremental Cost Effectiveness Ratios: Cost per psychiatric hospitalization or criminal justice system event avoided for INVEGA SUSTENNA vs OAPs: $17,391 A sensitivity analysis, varying total cost and effectiveness by ±20%, was conducted on the combined cost per CJS and psychiatric hospitalization events avoided. Incremental cost per CJS and psychiatric hospitalization event avoided ranged from $11,594 (20% lower costs and 20% greater efficacy) to $26,086 (20% greater costs and 20% lower efficacy) for the INVEGA SUSTENNA vs OAP group. Conclusion:* INVEGA SUSTENNA was associated with health resource and CJS cost reductions that partially offset the increased total drug cost in patients with schizophrenia enrolled in the PRIDE trial.
Morrison et al (2022)⁴⁴ evaluated the impact on healthcare costs and relapse rates of switching nonadherent patients from OAA to INVEGA SUSTENNA, and then transitioning to INVEGA TRINZA and/or INVEGA HAFYERA using a cost model. Data Source: Medicaid data *Sample size: Adult patients who were nonadherent to OAA and experienced recent relapse, n=7,454; young adults (aged 18-35 years) who were nonadherent to OAA, regardless of relapse, n=4,002 Total Cost Saved and Relapse Avoided (Nonadherent and Recently Relapsed Adults):* Relapse avoided at years 1, 2, and 3, respectively, were 225, 177, and 139 by switching 5% (n=373) of patients to INVEGA SUSTENNA; 450, 354, and 278 by switching 10% (n=745) of patients; and 2,252, 1,769, and 1,390 by switching 50% (n=3727) of patients. The total plan-level cumulative net cost savings yielded at years 1, 2 and 3, respectively, were $3.3M, $2.8M, and $2.2M when switching 5% of patients; $6.6M, $5.5M, and $4.3M when switching 10% of patients; and $33.1M, $27.5M, and $21.5M when switching 50% of patients. At year 1, 2, and 3, respectively, 1,126, 1,741, and 1,422 relapses were avoided by switching 50% of patients after the 1st subsequent relapse, and $15.2M, $25.9M, and $21.3M total cumulative net cost savings of were yielded. *Total Cost Saved and Relapse Avoided (Nonadherent, Young Adults):* Relapse avoided at years 1, 2 and 3, respectively, were 70, 59, and 49 by switching 5% (n=200) of patients to INVEGA SUSTENNA; 140, 117, and 98 by switching 10% (n=400) of patients; and 704, 586, and 488 by switching 50% (n=2001) of patients. The total plan-level cumulative net cost savings yielded at years 1, 2 and 3, respectively, were $646,000, $623,000, and $514,000 when switching 5% of patients; $1.3M, $1.2M, and $1.0M when switching 10% of patients; and $6.5M, $6.2M, and $5.1M when switching 50% of patients. At year 1, 2, and 3, respectively, 231, 478, and 465 relapses were avoided by switching 50% (n=2001) of patients after the 1st relapse, and $1.3M, $4.0M, and $4.2M total cumulative net cost savings were yielded. *Cost:* Switching 5%, 10%, or 50% of nonadherent, recently relapsed adults to INVEGA SUSTENNA prior to a subsequent relapse resulted in cost savings per patient switched of $8,884 at year 1, $7,391 at year 2, and $5,780 at year 3, respectively. Switching 5%, 10%, or 50% of nonadherent young adults to INVEGA SUSTENNA prior to a subsequent relapse resulted in cost savings per patient switched of $3,227 at year 1, $3,112 at year 2, and $2,570 at year 3, respectively. *Conclusion:* Switching nonadherent, recently relapsed patients to INVEGA SUSTENNA before subsequent relapse yielded substantial cost savings and avoided relapses.
Abbreviations: CJS, criminal justice system; OAA, oral atypical antipsychotic; OAP, oral antipsychotic.

Registry Data

Pharmacoeconomic outcomes, including hospitalizations and clinical event outcomes, were assessed from registry data.¹^,²^,⁴⁵ Results from the REACH OUT study are summarized in the Table: Registry Data.

Registry Data

Joshi et al (2015)¹^,² assessed the probability of relapse and hospitalization/ER utilization in adult patients treated with INVEGA SUSTENNA or OAAPs for the treatment of schizophrenia in the REACH OUT study. *Data Source: REACH OUT study supplemented with Truven Health MarketScan^®claims database to obtain matches for INVEGA SUSTENNA patients in REACH OUT that could not be matched with the original controls (July 31, 2009 – December 31, 2012). Relapse Definition: Number of relapse events (NRE): Total number of psychiatric or all-cause hospitalizations, visits to ERs, crisis centers and assertive community treatment. NRE>0 specified relapse. Calculation of overall mean relapse = probability of relapse in each group X mean number of relapse in groups with at least one relapse Propensity Matching* (Stuart and Rubin multiple control group technique): Model 1: Within REACH OUT, INVEGA SUSTENNA patients matched 1:1 with OAAP patients (C1:T) Expanded covariates; Propensity scores of receiving INVEGA SUSTENNA was estimated Model 2: Unmatched INVEGA SUSTENNA patients from Model 1 matched 1:1 with Supplemental Control OAAP patients (C2:T) Propensity score of receiving INVEGA SUSTENNA was estimated Model 3: Using matched OAAP to INVEGA SUSTENNA from Model 1, a 1:1 match was created based on propensity of receiving OAAPs in REACH OUT with Supplemental Control OAAP patients (C1:C2) C1:C2 used to adjust the outcomes of C2:T *Results* Final matched cohort (C1:T + C2:T): INVEGA SUSTENNA, n=258; OAAP, n=258 The INVEGA SUSTENNA vs OAAP group had a significantly lower mean probability of relapse (0.322 vs 0.473, respectively; P<0.001). Based on the mean NRE and probability of relapse, the estimated difference in number of relapses for those with an event was significantly lower for INVEGA SUSTENNA vs OAAP (- 0.105; P<0.001). Significantly lower odds of an inpatient event was observed in patients treated with INVEGA SUSTENNA vs an OAAP (OR: 0.62; 95% CI: 0.45 - 0.82).
Abbreviations: ER, emergency room; OAAP, oral atypical antipsychotic.

Joshi et al (2015)¹^,² assessed the probability of relapse and hospitalization/ER utilization in adult patients treated with INVEGA SUSTENNA or OAAPs for the treatment of schizophrenia in the REACH OUT study.
Data Source: REACH OUT study supplemented with Truven Health MarketScan^®claims database to obtain matches for INVEGA SUSTENNA patients in REACH OUT that could not be matched with the original controls (July 31, 2009 – December 31, 2012).
Relapse Definition:

Number of relapse events (NRE): Total number of psychiatric or all-cause hospitalizations, visits to ERs, crisis centers and assertive community treatment.
NRE>0 specified relapse.
Calculation of overall mean relapse = probability of relapse in each group X mean number of relapse in groups with at least one relapse

Propensity Matching (Stuart and Rubin multiple control group technique):

Model 1: Within REACH OUT, INVEGA SUSTENNA patients matched 1:1 with OAAP patients (C1:T)
- Expanded covariates; Propensity scores of receiving INVEGA SUSTENNA was estimated
Model 2: Unmatched INVEGA SUSTENNA patients from Model 1 matched 1:1 with Supplemental Control OAAP patients (C2:T)
- Propensity score of receiving INVEGA SUSTENNA was estimated
Model 3: Using matched OAAP to INVEGA SUSTENNA from Model 1, a 1:1 match was created based on propensity of receiving OAAPs in REACH OUT with Supplemental Control OAAP patients (C1:C2)
- C1:C2 used to adjust the outcomes of C2:T

Results Final matched cohort (C1:T + C2:T): INVEGA SUSTENNA, n=258; OAAP, n=258

The INVEGA SUSTENNA vs OAAP group had a significantly lower mean probability of relapse (0.322 vs 0.473, respectively; P<0.001).
Based on the mean NRE and probability of relapse, the estimated difference in number of relapses for those with an event was significantly lower for INVEGA SUSTENNA vs OAAP (- 0.105; P<0.001).
Significantly lower odds of an inpatient event was observed in patients treated with INVEGA SUSTENNA vs an OAAP (OR: 0.62; 95% CI: 0.45 - 0.82).

Abbreviations: ER, emergency room; OAAP, oral atypical antipsychotic.

Healthcare Resource Utilization and Cost Outcomes Evidence for INVEGA SUSTENNA vs Other Long-acting Injectable Antipsychotics

A study assessing hospitalization and rehospitalization rates and ER visits for INVEGA SUSTENNA vs long-acting injectable antipsychotic medications has been conducted. Results are summarized in Table: Healthcare Resource Utilization and Cost Outcomes Evidence for INVEGA SUSTENNA vs Other Long-acting Injectable Antipsychotics.

Healthcare Resource Utilization and Cost Outcomes Evidence for INVEGA SUSTENNA vs Other Long-acting Injectable Antipsychotics

Joshi et al (2016)⁴⁶ conducted a retrospective study assessing the impact of treatment with INVEGA SUSTENNA vs RLAI on healthcare costs and resource utilization over a 12-month follow-up period among eligible patients with schizophrenia. *Data Sources:* Truven Health MarketScan^® Multi-State Medicaid Database (July 1, 2007 – December 31, 2012) *Sample size after PSM: INVEGA SUSTENNA: n=499; RLAI: n=499 Outcomes: Patients treated with INVEGA SUSTENNA vs RLAI: Were less likely to be hospitalized (aOR: 0.72; 95% CI: 0.55-0.95; P=0.020) but were more likely to have physician office visits (aOR: 1.48; 95% CI: 1.01-2.18; P=0.047). Had a shorter inpatient length of stay (aIRR: 0.86; 95% CI: 0.82-0.90; P<0.001) and fewer ER visits (aIRR: 0.67; 95% CI: 0.61-0.73; P<0.001) but a greater number of physician office visits (aIRR: 1.54; 95% CI 1.50-1.59; P<0.001). Significantly lower discontinuation rates (36.5% vs 53.3%; P<0.001) and longer mean days of LAI coverage (233.6 vs 131.7 days; P<0.001) were observed in the INVEGA SUSTENNA vs RLAI cohort, respectively. Patients treated with INVEGA SUSTENNA vs RLAI were more likely to be adherent to therapy based on medication possession ratio (aOR: 12.5 [95% CI: 9.0-17.8]; P<0.001) and proportion of days covered (aOR: 11.7 [95% CI: 8.0-17.4]; P<0.001). Compared to RLAI, INVEGA SUSTENNA patients had lower monthly all-cause inpatient hospitalization (-$77.58; P=0.038) and ER (-$9.77; P=0.021) costs, but higher pharmacy costs ($318.67; P<0.001; do not account for discounts or rebates). Total all-cause monthly cost (including pharmacy cost) was higher for INVEGA SUSTENNA vs RLAI, however the difference was not statistically significant ($114.34; P=0.068). The authors partially attributed the higher prescription cost to the higher adherence rate observed for INVEGA SUSTENNA. Conclusion:* INVEGA SUSTENNA was associated with significantly lower inpatient admissions, shorter lengths of inpatient stay and fewer ER visits compared to RLAI. Patients treated with INVEGA SUSTENNA also experienced lower inpatient and ER costs, but relatively higher pharmacy costs.
Joshi et al (2015)⁴⁷ conducted a retrospective study assessing the impact of treatment with INVEGA SUSTENNA vs HAL decanoate on healthcare costs and resource utilization among eligible patients with schizophrenia. To improve generalizability by retaining all patients in the analysis while adequately adjusting for baseline demographics, comorbidities and healthcare resource utilization differences, an IPTW analysis was conducted. *Data Sources:* Truven Health MarketScan^® Multi-State Medicaid Database (July 1, 2007 – December 31, 2013) *Sample size* *after IPTW: INVEGA SUSTENNA: n=438; HAL decanoate: n=450 Outcomes: Patients treated with INVEGA SUSTENNA vs HAL decanoate: Had fewer ER visits (mean: 1.8 vs 2.8, respectively; P=0.01) but were more likely to have physician office visits (mean: 23.75 vs 16.9; P<0.01). Patients receiving INVEGA SUSTENNA vs HAL decanoate had higher adherence and lower discontinuation rates. Compared to HAL decanoate, INVEGA SUSTENNA patients had lower ER costs ($104 vs $66, respectively; P<0.05) but higher prescription medication ($435 vs $1,245, respectively; P<0.05) and total all-cause healthcare costs ($2,164 vs $3,034, respectively; P=NS). However, greater adherence and lower discontinuation rates among INVEGA SUSTENNA patients may have contributed to the drug and total healthcare cost differences observed. Conclusion:* Patients treated with INVEGA SUSTENNA experienced fewer ER visits and relatively lower ER costs, compared to those treated with HAL decanoate.
Abbreviations: aIRR, adjusted incidence rate ratio; aOR, adjusted odds ratio; CI, confidence interval; ER, emergency room; HAL, haloperidol; IPTW, inverse probability of treatment weighting; LAI, long-acting injectable antipsychotics; OAAP, oral atypical antipsychotics; PSM, propensity score matching; RLAI, risperidone long-acting injection.

Additional references assessing health outcomes using pooled data for long-acting injectable atypical antipsychotics have been referenced for your convenience.¹⁶^,⁴⁸^,⁴⁹

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources including internal/external databases) pertaining to this topic was conducted on 02 January 2024.

Health economic modeling, cost-effectiveness analyses using QALYs or health economic assessment questionnaires, review articles and studies focusing on adherence have not been included in this response.

References

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