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(paliperidone palmitate)

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This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

INVEGA SUSTENNA® (paliperidone palmitate)

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Use of INVEGA SUSTENNA in Recently Diagnosed Patients with Schizophrenia

Last Updated: 06/23/2024

Summary

In a randomized, active-controlled, rater-blinded, open-label, 24-month, multicenter study, INVEGA SUSTENNA significantly delayed time to relapse (hazard ratio [HR]: 1.5, 95% Confidence interval [CI], 1.1-2.2; P=0.0191) compared to oral antipsychotics (OAPs) in patients with recently diagnosed (≤5 years) schizophrenia. The 85th percentile for time-to-relapse was 469 vs 249 days, respectively. A total of 52 (14.8%) patients in the INVEGA SUSTENNA group relapsed compared to 76 (20.9%) in the OAP group resulting in a relative risk reduction of 29.4% for the INVEGA SUSTENNA arm.¹
Post hoc analyses of several clinical trials have been conducted to evaluate the efficacy and tolerability of INVEGA SUSTENNA in patients recently diagnosed with schizophrenia. Some analyses defined recently diagnosed as a schizophrenia diagnosed ≤3 years² and other as ≤5 years³^-⁷. In several of the post hoc analyses, the recently diagnosed population with schizophrenia was compared with a more chronically ill population with schizophrenia.²^,³^,⁵^,⁷^-⁹ See Table: Post hoc analyses for more details on these analyses.
In a real-world, mirror-image study conducted in patients with recent onset schizophrenia, treatment with INVEGA SUSTENNA significantly reduced the mean Clinical Global Impressions-Severity (CGI-S) score (P<0.001) and Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS) score (P<0.001).¹⁰

DOSAGE STRENGTH INFORMATION

Doses of paliperidone palmitate extended-release injectable suspension may be expressed in milligram equivalents of paliperidone (active moiety) or milligrams of paliperidone palmitate. Dosage information in this response has been converted to mg of paliperidone palmitate to reflect the commercially available dosage strengths in the United States. The conversion factor from mg eq to mg is 1.56.

INVEGA SUSTENNA doses expressed as 39, 78, 117, 156, and 234 mg of paliperidone palmitate are equal to 25, 50, 75, 100, and 150 mg eq of paliperidone, respectively.

CLINICAL STUDIES

PROSIPAL

Schreiner et al (2015)¹ conducted a 24-month, randomized, rater-blinded, prospective, open-label, international study (PROSIPAL) comparing treatment outcomes, including time to relapse, among patients receiving OAPs vs INVEGA SUSTENNA for recently diagnosed (≤5 years) schizophrenia.

Study Design/Methods

Inclusion criteria: Prior treatment with antipsychotics and a history of ≥2 relapses requiring hospitalization (including current acute episode; Positive and Negative Syndrome Scale [PANSS] 70-120) within 24 months of enrollment.
Key exclusion criteria: Treatment with clozapine during the last 3 months prior to study initiation or treatment with a long-acting antipsychotic within 3 injection cycles prior to screening.
Treatment Design
- Following randomization (1:1) to INVEGA SUSTENNA or OAPs, patients entered an initial 2-week acute oral treatment phase.
  - Prior treatments tapered off over a maximum of 7 days.
  - Patients randomized to INVEGA SUSTENNA group received paliperidone extended-release (ER) 3-12 mg daily.
  - Patients randomized to OAP group received a newly selected OAP (aripiprazole, olanzapine, quetiapine, paliperidone ER, risperidone or haloperidol) at a dose defined by the investigator and within the locally approved dose range.
- Patients who responded (score ≤4 for at least four of the following PANSS items: P1 (delusions); P2 (conceptual disorganization); P3 (hallucinatory behavior); P6 (suspiciousness/persecution); P7 (hostility); G8 (uncooperativeness), a CGI-S score ≤4 plus no significant intolerable side effects to study medication) to initial treatment entered the core 24-month treatment phase.
  - Patients in the INVEGA SUSTENNA group were converted to INVEGA SUSTENNA in the following manner: Initial injection of 234 mg on day 1 (deltoid), 156 mg on day 8 (deltoid), 117 mg on day 38 (deltoid or gluteal) and then flexible-dosing (39-234 mg) once monthly (deltoid or gluteal).
  - Patients in the OAP group continued therapy from the initial phase.

Results

Patient Characteristics

Results and demographics are reported for the core intent-to-treat (ITT) population (acute phase responders who received at least one dose of study medication and had at least one post-baseline efficacy or safety assessment during the core treatment phase).
No significant differences were observed between treatment groups with regard to baseline/demographic characteristics (N=715; mean age: 32.6 years; 57.9% male).
Mean modal doses of individual APs are listed in the Table: Dosing Information (Core ITT Population).

Dosing Information (Core ITT Population)¹

	INVEGA SUSTENNA (n=352)	ARI (n=81)	HAL (n=34)	OLA (n=49)	PAL (n=77)	QUE (n=65)	RIS (n=57)
Mean Modal Dose, mg	158.7^a	19.1	8.2	12.9	7.5	489.2	4.3
Abbreviations: ARI, aripiprazole; HAL, haloperidol; OLA, olanzapine; PAL, paliperidone ER; QUE, quetiapine; RIS, risperidone. ^aMean maintenance dose (fourth injection onwards); 91.5% (322/352) received INVEGA SUSTENNA according to appropriate study protocol dosing schedule.

Efficacy

Mean time to relapse was significantly longer for the INVEGA SUSTENNA vs OAP group (HR: 1.5, 95% CI, 1.1-2.2; P=0.0191). The 85^th percentile for time-to-relapse was 469 vs 249 days, respectively.
A total of 52 (14.8%) patients in the INVEGA SUSTENNA group relapsed compared to 76 (20.9%) in the OAP group over the 24-month treatment phase (P=0.0323).
- Relative risk reduction of 29.4% in the INVEGA SUSTENNA group.
Both treatment groups experienced significant reductions in PANSS total scores from baseline to each subsequent visit, with significant between group differences observed at day 8.
- Baseline to day 8: INVEGA SUSTENNA -4.8 vs OAPs -3.7; P=0.0213 vs OAP
- Baseline to last observation carried forward (LOCF) endpoint: INVEGA SUSTENNA -16.6 vs OAPs -14.1; P=0.0745 vs OAP
At LOCF endpoint, a ≥30% improvement in PANSS scores was observed in 75.6% and 69.4% of patients in the INVEGA SUSTENNA and OAP groups, respectively (P=0.0786).
The percentages of INVEGA SUSTENNA and OAP patients with CGI-S scores rated “mildly ill” at baseline were 14.0% and 16.1%, respectively compared to LOCF endpoint results of 65.4% and 65.0%, respectively.
Mean Personal and Social Performance (PSP) scores significantly improved from baseline to LOCF endpoint for both treatment groups (P<0.0001), with no significant between group differences (mean change scores: INVEGA SUSTENNA 9.8; OAPs: 8.7; P=0.2831).
Significant improvements from baseline to each time point in Subjective Wellbeing under Neuroleptics – short form (SWN-S) total scores were observed for both treatment groups. However, significant improvements were observed among patients in the INVEGA SUSTENNA group compared to patients in the OAP group with regard to several aspects of patient medication satisfaction (TSQM sub-scores) and physician’s treatment satisfaction.

Safety

An overview of safety results is provided in the Table: Safety Analysis.

Safety Analysis¹

	INVEGA SUSTENNA (n=352)	OAPs (n=363)
Experienced ≥1 TEAE, (%)	71.3	62.0
Experienced ≥1 serious TEAE (%)	11.6	12.7
TEAEs leading to discontinuation, n (%)	14 (4.0)	11 (3.0)
TEAEs affecting ≥5% of patients in any group, n (%)
Weight increase	56 (15.9)	63 (17.4)
Headache	39 (11.1)	31 (8.5)
Insomnia	34 (9.7)	29 (8.0)
Schizophrenia	29 (8.2)	35 (9.6)
Nasopharyngitis	25 (7.1)	18 (5.0)
Injection site pain	24 (6.8)	0
Anxiety	20 (5.7)	16 (4.4)
Tremor	18 (5.1)	8 (2.2)
Suicidal ideation	16 (4.5)	20 (5.5)
Abbreviations: OAPs, oral antipsychotics; TEAE, treatment-emergent adverse event.

A similar proportion of INVEGA SUSTENNA and OAP patients experienced a hyperprolactinemia TEAE and/or at least one potentially prolactin-related TEAE (6.3% vs 5.0%, respectively).
Mean change in weight from baseline to LOCF endpoint: INVEGA SUSTENNA=2.3 kg; OAPs=1.9 kg
- Proportion of patients experiencing ≥7% increase in body weight from baseline to LOCF endpoint: olanzapine (37.5%); risperidone (26.8%); aripiprazole (23.5%); INVEGA SUSTENNA (20.6%); paliperidone ER (19.7%); quetiapine (15.4%); haloperidol (11.8%)

Safety and Efficacy - Asian/Australian Patients

Zhang et al (2015)¹¹ conducted a phase 3b, open-label, multicenter study evaluating the safety and efficacy of INVEGA SUSTENNA in Asian/Australian patients with recent-onset (≤5 years) schizophrenia who previously failed treatment with OAPs.

Following a ≤7-day screening and washout period, patients entered into an 18-month treatment phase where they received initiation doses of INVEGA SUSTENNA (234 mg on day 1 and 156 mg on day 8, deltoid IM) followed by flexible once-monthly injections of 78234 mg (deltoid IM or gluteal IM).

The ITT/safety population of 521 patients (mean age: 28.7 years; 65.5% male) received a mean maintenance INVEGA SUSTENNA dose of 157.2 mg for a mean exposure duration of 382.6 days. From baseline to endpoint, INVEGA SUSTENNA patients experienced a significant reduction in PANSS total scores (-11.3; P<0.0001). Patients with baseline PANSS total scores ≥70 vs <70 experienced significantly greater mean changes at endpoint (-23.1 vs -4.7, respectively; P<0.0001). At each visit the percentage of treatment responders (≥30% reduction in PANSS total score) increased (day 38: 35.5%; day 548: 73.9%). Symptom remission was observed in 33.3% of patients at endpoint (Results significant beginning at month 6; P<0.0001).

Overall, 82.3% of INVEGA SUSTENNA patients experienced at least one TEAE. The most commonly reported TEAEs (≥10%), primarily mild to moderate in intensity, were: injection site pain (18.6%), insomnia (15.2%), akathisia (13.4%) and headache (11.3%). The proportion of patients with injection site pain decreased from 17.1% during week 1 to 1.3% by the end of month 1. Extrapyramidal symptoms (EPS)-related events (primarily nonserious and mild to moderate in intensity), were reported in 31.3% of patients. EPS-related TEAEs observed in ≥5% of patients were: akathisia (13.4%), tremor (6.3%), and restlessness (5%). Three patients (0.6%) discontinued treatment due to akathisia. EPS was more common in patients from China (41.7%) and the Philippines (35.7%). Prolactin-related TEAEs occurred in 62 (11.9%) patients and were more common in women (25.6%) vs men (4.7%). The most common (≥2%) prolactin-related TEAEs in women were amenorrhea (11.1%), menstrual disorder (5.6%), and hyperprolactinemia (4.4%). The most common TEAE in men was sexual dysfunction (2.1%). Mean change in body weight from baseline to month 18 was 3.91 kg (P<0.0001 vs baseline). A ≥7% increase in weight from baseline to endpoint was reported in 41.8% of patients.

A subgroup analysis of the Zhang et al (2015)¹¹ study assessing the safety and efficacy of INVEGA SUSTENNA in Taiwanese patients¹² and a post hoc analysis assessing the effect of INVEGA SUSTENNA on hospitalization risk¹³ after switching from OAPs have been referenced for your convenience.

See Table: Post Hoc Analyses.

Post Hoc Analyses

Study Design	Results
Sajatovic et al (2024)⁹ conducted a post hoc analysis to evaluate the overall risk of relapse by duration of illness (0-3 years, >3-5 years, and >5 years) in adult patients with schizophrenia who received INVEGA SUSTENNA or OAP in the PRIDE and PROSIPAL studies, which were multicenter, prospective, randomized, open-label, flexible-dose studies. PRIDE was an event-monitoring board-blinded, parallel-group study. PROSPIAL was an active-controlled, rater-blinded, international study. A total of 1157 patients (male, 68.7%; mean age, 34.7 years) were included: 0-3 years group: INVEGA SUSTENNA, n=253; OAP, n=263 >3-5 years group: INVEGA SUSTENNA, n=138; OAP, n=134 >5 years group: INVEGA SUSTENNA, n=187; OAP, n=182	Efficacy Fewer relapses were reported in the patients who received INVEGA SUSTENNA vs OAP (25.2% vs 32.9%). The overall risk of relapse was reduced by 31% in the patients who received INVEGA SUSTENNA vs OAP (HR, 0.69; 95% CI, 0.56-0.86; P<0.001). Reductions in the risk of relapse by duration of illness for patients receiving INVEGA SUSTENNA vs OAPs were: 0-3 years group: 33% reduction (HR, 0.67; 95% CI, 0.44-1.00; P=0.050) >3-5 years group: 43% reduction (HR, 0.57; 95% CI, 0.35-0.93; P=0.025) >5 years group: 26% reduction (HR, 0.74; 95% CI, 0.55-1.00; P=0.049) Safety The most common TEAEs (≥10%) were injection site pain, nasopharyngitis, weight increase, akathisia, headache, anxiety, insomnia, and schizophrenia. A total of 875 (75.6%) patients experienced a TEAE: 0-3 years group: INVEGA SUSTENNA, n=197 (77.9%); OAP, n=182 (69.2%) >3-5 years group: INVEGA SUSTENNA, n=99 (71.7%); OAP, n=93 (69.4%) >5 years group: INVEGA SUSTENNA, n=155 (82.9%); OAP, n=149 (81.9%)
Lopena et al (2023)⁸ conducted a post-hoc analysis to assess the efficacy and safety of paliperidone palmitate 1-month or 3-month LAI vs OAP treatments in adult patients diagnosed with schizophrenia and varying duration of illness (0-3 years [PP, n=294; OAP, n=312] and >3 years [PP, n=325; OAP, n=316]) using data obtained from the PRIDE, PROSIPAL, and DREaM studies, which were multicenter, prospective, randomized, open-label, flexible-dose studies. PRIDE was an event-monitoring board-blinded, parallel-group study. PROSPIAL was an active-controlled, rater-blinded, international study. DREaM was a delayed-start, matched-control study.	Efficacy Fewer treatment failures were observed with paliperidone palmitate vs OAP: 0-3 years - 17.7% and 25.3%, respectively >3 years - 32.3% and 42.4%, respectively Time to first treatment failure was significantly longer with paliperidone palmitate vs OAP treatment in both duration of illness groups: 0-3 years group, HR=0.67, 95% CI, 0.47-0.95, P=0.026 >3 years group, HR=0.69, 95% CI, 0.53-0.89, P=0.004 Safety A total of 957 (76.7%) patients experienced a TEAE: 0-3 years - PP: n=235 (79.9%), OAP: n=226 (72.4%) >3 years - PP: n=254 (78.2%), OAP: n=242 (76.6%) The most common TEAEs were weight increase, insomnia, headache, and injection site pain (PP only).
Si et al (2017)⁷ conducted post hoc analyses on data obtained from two studies: PREVAIL¹⁴ (Study 1): Phase IV, 3-month, single arm, open label, prospective, non-comparable study SUSTAIN¹¹ (Study 2): Phase IIIb, 18-month, single arm, open-label, multicenter study Treatment Groups: Study 1 stratified patients (N=212) as recently diagnosed (≤5 years; n=88; mean age=34.2 years; 51.14% male) and chronic schizophrenia (>5 years; N=124; mean age=39.2 years; 50.81% male). Mean time since diagnosis was 1.8 years (recently diagnosed) and 12.6 years (chronic). Recently diagnosed patients in Study 1 were further divided in to more recently diagnosed (≤2 years; n=50; mean age=35 years; 48% male) and less recently diagnosed schizophrenia (2-5 years; n=38; mean age=33.2 years, 55.265% male). Mean time since diagnosis is 0.4 years (more recently diagnosed) and 3.5 years (less recently diagnosed). Study 2 stratified patients (N=517) as more recently diagnosed (≤2 years; n=273; mean age=28 years, 65.2% male) and less recently diagnosed schizophrenia (2-5 years; n=244; mean age 29.4 years; 65.98% male). Mean time since diagnosis was 0.7 years (more recently diagnosed) and 3.4 years (less recently diagnosed). Only included patients with recently diagnosed (≤5 years) schizophrenia. Treatments: OAP were discontinued before initiating INVEGA SUSTENNA. Patients received flexibly-dosed INVEGA SUSTENNA (78-234 mg) after standard initiation regimen.	Efficacy In both Study 1 and Study 2, a significant change in total mean PANSS score from baseline to endpoint was observed for more recently and less recently diagnosed patients. Study 1 Improvement in PANSS total score from baseline to endpoint was significantly greater in patients with recently diagnosed vs chronic schizophrenia (mean change from baseline: -30 [95% CI, -34.37 to -25.56] vs -19.6 [95% CI, -23.33 to -15.85], P=0.0005). There was no statistical difference in PANSS total score between less recently diagnosed vs more recently diagnosed schizophrenia (P=0.8867) at study end. Change in mean CGI-S score from baseline to endpoint was significantly greater in patients with recently vs chronic schizophrenia (P=0.0008). Study 2 There was no statistical difference in PANSS total score between less recently diagnosed vs more recently diagnosed schizophrenia (P=0.0659) at study end. Change in mean CGI-S score from baseline to endpoint was significantly greater in more recently diagnosed vs less recently diagnosed patients (P=0.0353). Safety Study 1 69.3% patients with recently diagnosed and 62.9% patients with chronic schizophrenia experienced at least one TEAE. 5.7% patients with recently diagnosed and 6.5% patients with chronic schizophrenia discontinued study drug. There were no deaths reported. Study 2 83.2% patients with recently diagnosed and 82.4% patients with less recently diagnosed schizophrenia experienced at least one TEAE. 12.5% patients with more recently diagnosed and 13.1% patients with less recently diagnosed schizophrenia discontinued the study drug due to TEAEs. There were 2 deaths (suicide [n=1] and pulmonary embolism [n=1]). The deaths were considered to be unrelated to study drug.
In a subgroup analysis of a prospective, randomized, OL, event monitoring board-blinded, 15-month trial¹⁵ in patients with a history of CJS involvement, Alphs et al (2015)³ evaluated the time to first treatment failure in patients with recent-onset (≤5 years) vs chronically ill (>5 years) schizophrenia treated with INVEGA SUSTENNA or OAPs. Mean duration of illness: recent (3.0 years); chronically ill (18.7 years) Treatment Groups: Recent-Onset: INVEGA SUSTENNA (n=42): mean age=30.8 years; 90.5% male; 73.8% Black OAP (n=35): mean age=32.8; 94.3% male; 62.9% Black Chronic: INVEGA SUSTENNA (n=183); mean age=39.2; 84.2% male; 62.3% Black OAP (n=182); mean age=39.7 years; 85.7% male; 59.1% Black Treatments: Patients were stratified on the basis of their selection of OAP treatments and randomly assigned to flexibly dosed INVEGA SUSTENNA (78-234 mg) or flexibly dosed OAP therapy (ARI; HAL; OLA; PAL; PER; QUE; or RIS). Mean INVEGA SUSTENNA doses for the recent vs chronic subgroups were 178.5 mg vs 181.8 mg, respectively.	Efficacy: Risk for treatment failure was lower for INVEGA SUSTENNA vs OAP in both subpopulations, with a lower risk observed in the recent-onset group. Recent-onset: INVEGA SUSTENNA (33.3%) vs OAPs (54.3%); HR: 1.73; 95% CI, 0.87-3.45); P=0.121 Chronic: INVEGA SUSTENNA (41.5%) vs OAPs (53.8%); HR: 1.37; 95% CI, 1.02-1.85; P=0.039 Median time to 1st treatment failure: No major differences were observed between subgroups with regard to reasons for 1st treatment failure. Recent-onset (INVEGA SUSTENNA: not estimable vs OAPs: 270 days) Chronic (INVEGA SUSTENNA: 416 days vs OAPs: 210 days) Safety: Incidence of TEAEs (INVEGA SUSTENNA vs OAPs, respectively): Recent-onset (90.5% vs 77.1%) Chronic (84.7% vs 80.2%) The most common TEAEs (≥10%) in both treatment groups: injection site pain (INVEGA SUSTENNA only), increased body weight, akathisia, insomnia, anxiety, sedation, back pain and headache Prolactin-related TEAEs were more frequent with INVEGA SUSTENNA vs OAP for both subgroups, respectively: Recent-onset (28.6% vs 2.9%) Chronic (22.4% vs 4.4%) In addition, weight increases (≥7%) were more frequent with INVEGA SUSTENNA vs OAP for both subgroups, respectively: Recent-onset (38.1% vs 18.2%) Chronic (30.7% vs 13.7%)
Fu et al (2014)⁴ conducted a post hoc analysis of a 13 week, DB, double-dummy, multicenter comparative study¹⁶ between INVEGA SUSTENNA and RLAI focusing on adults recently diagnosed with schizophrenia (≤5 years). Treatment Groups: INVEGA SUSTENNA (n=161; mean age: 30.5 years; 66.5% male): Deltoid injection of INVEGA SUSTENNA 234 mg on day 1 followed by a 156-mg deltoid injection on day 8; thereafter, patients received flexibly dosed INVEGA SUSTENNA injections on days 36 (78 or 156 mg) and 64 (78, 156, or 234 mg) in either the deltoid or gluteal muscle (mean final dose: 173 mg monthly). Optional supplementation with RIS was permitted under certain circumstances outlined in the protocol. RLAI (n=173; mean age: 30.8 years; 66.5% male): RLAI 25 mg on days 8 and 22, followed by 25 or 37.5 mg on days 36 and 50; thereafter, patients received flexible doses of 25, 37.5, or 50 mg on days 64 and 78, all in the gluteal muscle (mean final dose: 31.4 mg biweekly). Oral supplementation with RIS (1-6 mg) was administered for the first 28 days.	Efficacy: Significant changes were observed in the mean PANSS total score from baseline to day 22 for both INVEGA SUSTENNA and RIS (INVEGA SUSTENNA, -10.1; P<0.001; RIS, -11.3; P<0.001), beginning at day 4. LS mean PANSS total score changes from baseline to endpoint were similar for the INVEGA SUSTENNA (-17.9) and RLAI (-17.8) group At endpoint, responder rates (≥30% improvement in PANSS total score) were 55.3% for INVEGA SUSTENNA and 54.3% for RLAI (P=0.863). Safety: During days 1-22, at least one adverse event was reported by 37.3% patients in INVEGA SUSTENNA group vs 30.1% in the RIS group. Headache, anxiety, injection site pain, insomnia, akathisia, somnolence and exacerbation of schizophrenia were the most common AEs (≥2%) reported in the INVEGA SUSTENNA vs RIS groups, respectively, with no significant between group differences with regard to incidence. From baseline to endpoint, 54.7% patients in INVEGA SUSTENNA group vs 50.3% in RLAI group experienced at least one adverse event. Headache, exacerbation of schizophrenia, insomnia, anxiety and increased weight were the most common AEs (≥5%) reported in the INVEGA SUSTENNA vs RIS groups, respectively. A significant difference in the incidence of anxiety was observed between RLAI and INVEGA SUSTENNA (1.7% vs 68%; RR: 0.25; 95% CI, 0.07-0.89). Over the entire study, no EPS-related AEs were reported in ≥5% of patients and no significant between-group differences were observed. LS mean weight change in the RLAI and INVEGA SUSTENNA group were 1.53 kg and 1.62 kg, respectively. At endpoint, the LS mean increase in prolactin was 12.2 ng/mL and 17.5 ng/mL for females in the INVEGA SUSTENNA and RLAI groups, respectively while the values for men were 8.5 ng/mL and 6.3 ng/mL respectively.
Hargarter et al (2013)² compared the efficacy and safety of INVEGA SUSTENNA in recently diagnosed (≤3 years; n=233; mean age: 32.2 years; 63.9% male) vs chronic (≥3 years; n=360; mean age: 42.4 years; 62.5% male) non-acute, symptomatic patients with schizophrenia unsuccessfully treated with OAPs who participated in a 6 month, international, prospective, OL study.¹⁷ Transition from OAPs: After tapering off OAPs over ≤4 weeks, INVEGA SUSTENNA was initiated at 234 mg on day 1 and 156 mg on day 8 (±2 days), both administered IM in the deltoid muscle. Flexible INVEGA SUSTENNA doses of 78-234 mg were administered monthly thereafter (±7 days). The mean modal INVEGA SUSTENNA doses were 153.7 mg and 161.2 mg for recently diagnosed and chronic patients, respectively. Patients receiving CLOZ within 3 months of trial initiation were not eligible to participate.	Efficacy: At LOCF endpoint, a significantly greater percentage of recently diagnosed patients experienced a ≥20% decrease in PANSS total score vs chronic patients (71.4% vs 59.2%, respectively; P=0.0028 between groups). Mean PANSS total scores, from baseline to LOCF endpoint, significantly decreased for both treatment groups (recent: -15.1, P<0.001; chronic: -9.6, P<0.001). This change was significantly greater in recently diagnosed vs chronic patients (P<0.0001). From baseline to LOCF endpoint both treatment groups experienced significant improvements in mean PANSS subscale and CGI-S scores, with significantly greater improvements observed in recently diagnosed vs chronic patients. Safety: At least one TEAE, primarily mild to moderate in intensity, was observed in 61.4% and 58.6% of recently diagnosed vs chronic patients, respectively. TEAEs occurring in ≥5% of recently diagnosed vs chronic patients, respectively, were injection site pain (12.9% vs 11.9%); insomnia (9.9% vs 7.8%); anxiety (6.4% vs 6.9%); headache (6.0% vs 5.3%); akathisia (5.6% vs 4.2%); somnolence (5.2% vs 3.9%); weight increased (5.2% vs 1.9%); depression (5.2% vs 1.7%); and psychotic disorder (4.7% vs 6.9%). Mean change in ESRS, from baseline to LOCF endpoint, was -0.9 and -1.4 for recent vs chronic patients, respectively (P<0.0001, both groups). Baseline to LOCF endpoint mean weight change was 1.4 kg for recently diagnosed patients vs 1.0 kg for chronic patients.
Sliwa et al (2012)⁵ conducted a post hoc analysis of Hough et al (2010)¹⁸ and Gopal et al (2011)¹⁹ comparing the tolerability of INVEGA SUSTENNA in recently diagnosed vs chronically ill patients with schizophrenia who participated in a multiphase, long-term study. Treatment groups included patients with a recent diagnosis (≤5 years; n=216; mean age=31.0 years; 60.2% male) vs patients with a chronic diagnosis (>5 years; n=429; mean age = 40.6 years; 58.0% male), including only those treated continuously with INVEGA SUSTENNA during all study phases. Mean years of illness: recent (2.9 years); chronically ill (16.2 years) Tolerability measures included AE reports that occurred at a margin of ≥2% between treatment groups from baseline through months 1, 3, 6, 9, 12 and OLE endpoint. The trial consisted of 5 phases: ≤7 day screening/washout phase 9-week, OL transition phase (78 mg INVEGA SUSTENNA on days 1 and 8 followed by flexible dosing [39, 78 or 156 mg] beginning at week 5 24-week OL maintenance phase (39, 78 or 156 mg for the first 12 weeks followed by the established maintenance dose for the second 12 weeks) DB, PBO-controlled, relapse prevention phase of variable duration (up to 63 weeks) Optional OLE phase (up to 52 weeks) with flexible dosing (39, 78, 117 or 156 mg). The mean monthly dose for each treatment group was approximately 109 mg with a mean duration of exposure, 333.0 days and 308.7 days for recently diagnosed vs chronically ill patients, respectively.	Over the course of the trial, incidence rates, RRs and 95% CIs suggested that recently diagnosed patients were less likely to experience an adverse event compared to chronically ill patients. Potentially significant between group differences were observed for the following side effects: Nasopharyngitis was reported by significantly more patients with chronic vs recent illness at months 6, 9, 12 and OLE endpoint (OLE endpoint: 7.2% vs 2.8 %, respectively; RR: 0.38; 95% CI, 0.163-0.907). At OLE endpoint, recently diagnosed vs chronically ill patients reported significantly more influenza (2.8% vs 0.7%, respectively; RR: 3.97; 95% CI, 1.003-15.730) and amenorrhea (3.2% vs 0.9%, respectively; RR: 3.48; 95% CI, 1.029-11.744). AEs of Interest: At each assessment period, numerically lower rates of any EPS-related events were observed in recently diagnosed (2.3-9.3%) vs chronically ill patients (5.8-12.6%). LS mean weight change at endpoint was 2.6 kg for recently diagnosed patients vs 3.4 kg for chronically ill patients (P=0.42). Logistic and linear regression models revealed that these outcomes were not affected by between group differences in age, BMI, age at diagnosis, smoking status and race at baseline. While prolactin levels increased in both genders from both subgroups, the mean change from baseline to OLE endpoint was significantly greater in recently diagnosed vs chronically ill females (41.8 ng/mL vs 26.5 ng/mL, respectively; P=0.0002). Prolactin related adverse events were reported in 7.9% vs 3.5% of recently diagnosed vs chronically ill patients, respectively.
Bossie et al (2011)⁶ conducted a post hoc analysis of a 13-week DB study²⁰ assessing the tolerability of INVEGA SUSTENNA initiation doses in patients recently diagnosed (≤5 years; n=146; mean age=31.2 years; 68% male) with schizophrenia. Mean time since first schizophrenia diagnosis: 2.9 years INVEGA SUSTENNA Dosing - 13-Week Study: Initiation dose day 1 (deltoid IM): INVEGA SUSTENNA 234 mg (n=109); PBO (n=37) Fixed doses day 8, 36, and 64 (deltoid or gluteal IM): INVEGA SUSTENNA 234 mg (n=36); INVEGA SUSTENNA 156 mg (n=39); INVEGA SUSTENNA 39 mg (n=34); PBO (n=37) INVEGA SUSTENNA Dosing – Post Hoc Analysis: Initiation doses day 1 and day 8 (deltoid IM): INVEGA SUSTENNA 234 mg and 156 mg, respectively followed by 156 mg (deltoid or gluteal IM) on days 36 and 64 (n=39)	Efficacy: For the recently diagnosed subgroup, a significantly greater improvement in the PANSS total score, from baseline to endpoint, was observed for the INVEGA SUSTENNA 156 mg (-16.5) vs PBO (-2.2) groups (effect size vs PBO, LS mean score change: -0.7; 95% CI, -1.16 to -0.23; P=0.0031). Similar Results were observed for the overall study population (effect size vs PBO, LS mean score change: -0.5; 95% CI, -0.69 to -0.25; P=0.0001). Safety: Days 1-7 AE rates were 37.6% (41/109) for the INVEGA SUSTENNA group vs 29.7% (11/37) for the PBO group in the recently diagnosed subgroup. This compared to 38% (181/476) vs 43.1% (69/160), respectively, for the overall study population. AEs reported in ≥2% of recently diagnosed patients receiving INVEGA SUSTENNA (all 3 arms) and in a higher percentage vs PBO, respectively, were: injection site pain (5.5% vs 2.7%; RR: 2.0; 95% CI, 0.25-16.37); agitation (4.6% vs 2.7%; RR: 1.7; 95% CI, 0.21-14.06); and headache (3.7% vs 0.0%; RR: 3.1; 95% CI, 0.17-56.41). RRs were not statistically significant as per 95% CIs. Results were similar for the overall study population. Days 8-36 AE rates were 41.0% (16/39) for the INVEGA SUSTENNA 156 mg group vs 37.8% (14/37) for the PBO group in the recently diagnosed subgroup. This compared to 38.5% and 41.3%, respectively, for the overall study population. AEs reported in ≥5% of recently diagnosed patients receiving INVEGA SUSTENNA 156 mg and in a higher percentage vs PBO, respectively were: anxiety (5.1% vs 0.0%; RR: 4.8; 95% CI, 0.24-95.76). RR was not statistically significant as per 95% CI. No AEs met the above criteria for the overall study population. The LS mean weight change over the entire study for the recently diagnosed subgroup was 1.4 kg for the INVEGA SUSTENNA 156 mg group compared to 0.0 kg for the PBO group (P=0.157, LS mean difference). This compared to 0.7 kg and -0.3 kg for INVEGA SUSTENNA and PBO, respectively, for the overall study population (P=0.028, LS mean difference). Movement related AEs over the entire study for the recently diagnosed subgroup were reported by 10.3% (4/39) of the INVEGA SUSTENNA 156 mg group and 8.1% (3/37) of the PBO group, with no significant between group differences (P>0.05). This compared to 9.3% (15/161) and 8.1% (13/160) for INVEGA SUSTENNA and PBO, respectively, for the overall study population.
Abbreviations: AD, antidepressant; AE, adverse event; ARI, aripiprazole; CI, confidence interval; CGI-S, Clinical Global Impressions-Severity; CJS, Criminal Justice System; CLOZ, clozapine; DB, double-blind; EPS, extrapyramidal symptoms; ESRS, Extrapyramidal Symptom Rating Scale; HAL, haloperidol; HDRS, Hamilton Depression Rating Scale; HR, hazard ratio; IM, intramuscular; LOCF, last observation carried forward; LS, least squares; MS, mood stabilizer; OAP, oral antipsychotic; OL, open-label; OLA, olanzapine; OLE, open-label extension; PAL, paliperidone; PANSS, Positive and Negative Syndrome Scale; PBO, placebo; PER, perphenazine; QUE, quetiapine; RIS, risperidone; RLAI, risperidone long-acting injection; RR, risk ratio; TEAE, treatment emergent adverse event; YMRS, Young Mania Rating Scale.

Real World Study

Peitl et al (2022)¹⁰ conducted a real-world, mirror-image study evaluating the efficacy of INVEGA SUSTENNA on the frequency and length of hospitalizations and psychosis symptom severity in patients (N=112) with recent onset schizophrenia (diagnosed 1-2 year prior to enrollment and ≥1 psychiatric hospitalization in preceding 12 months). Patients that had been admitted for inpatient treatment between May 2017 and February 2019 were included. One-year follow up was completed at the end of March 2020. The mean (SD) duration of illness was 1.6 (0.3) years. A reduction in the mean (SD) CGI-S score from 5.2 (0.8) to 2.6 (0.5) (P<0.001) and CRDPSS score from 14.8 (4.3) to 8.6 (3.8) (P<0.001) was observed after initiation of INVEGA SUSTENNA. The average (SD) number of hospitalizations and the mean (SD) total number of hospitalization days in the year before starting INVEGA SUSTENNA was 1.1 (2.3) and 13.6 (5.8), respectively; these values significantly reduced to 0.3 (0.6; P=0.002) and 7.0 (6.4; P<0.001), respectively, in the next year.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENTdrug file (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 20 May 2024.

References

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