Summary

• Results from the United States National Institute of Mental Health Epidemiologic Catchment Area study estimated that 47% of all persons with a lifetime diagnosis of schizophrenia or schizophreniform disorder also met the criteria for some form of substance abuse or dependence.¹
• A diagnosis of active substance abuse/dependence within 3 months before screening was an exclusion criteria in the pivotal INVEGA SUSTENNA trials for both schizophrenia^2-6 and schizoaffective disorder.⁷
• Patients with a history of incarceration and comorbid substance abuse were included in a 15-month, prospective, randomized, open-label, event monitoring board (EMB)-blinded study (PRIDE: Paliperidone Palmitate Research In Demonstrating Effectiveness) which compared the effects of INVEGA SUSTENNA versus daily oral antipsychotics (oAP) on treatment failure in a community sample of schizophrenia patients.⁸ An exploratory analysis of the PRIDE study examined the effects of substance abuse on treatment failure and is described below.⁹

CLINICAL STUDIES

Starr et al (2018)⁹ conducted an exploratory analysis of the PRIDE trial examining the impact of substance abuse on treatment failure during a 15-month, prospective, randomized, open-label, EMB-blinded, multicenter US study designed to reflect real-world schizophrenia patients, treatments, and outcomes.

Study Design/Methods

The clinician and patient reviewed the list of available oAPs (aripiprazole, haloperidol, olanzapine, paliperidone, perphenazine, quetiapine and risperidone) before randomization and could preselect up to 6 from the list based on prior experience. 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.

Substance abusers were defined as those who reported substance or alcohol abuse in the past 30 days on the baseline Addiction Severity Index – Lite Version (ASI-Lite) or had a current MINI diagnosis of a substance abuse disorder.⁹ Patients abusing intravenous drugs within 3 months of screening and those with an opiate dependence disorder were excluded from the study.⁸

Select baseline characteristics are reported in the Table: Baseline Characteristics (ITT Analysis Set). A total of 1.9% (INVEGA SUSTENNA: 2.3%; oAP: 1.5%) and 2.2% (INVEGA SUSTENNA: 2.1%; oAP: 2.4%) patients in the substance abuse and nonabuse cohorts, respectively, discontinued treatment due to an AE.

Polysubstance abuse was highly prevalent in the substance abuse cohort (61.7% [161/261]) vs the nonabuse cohort (45.6% [68/149]), who did not meet the study criteria for substance abuse despite this use. The most commonly used substances in the substance abuse cohort (past 30 days or lifetime, n=261), according to the ASI-Lite, were: alcohol (95%), cannabis (85.4%), cocaine (62.5%), and amphetamines (29.5%).

Efficacy

For both cohorts, a higher risk of treatment failure was observed with oAP vs INVEGA SUSTENNA therapy. Hazard ratio (oAP vs INVEGA SUSTENNA):

• Substance Abuse: 1.48 (P=0.016)
• Nonabuse: 1.77 (P=0.015)

Treatment failure rate per cohort and treatment group:

• Substance Abuse: INVEGA SUSTENNA, 56.2%; oAP, 64.2%
• Nonabuse: INVEGA SUSTENNA, 36.5%; oAP, 53.6%

Median time to treatment failure per cohort and treatment group:

• Substance Abuse: INVEGA SUSTENNA, 291 days; oAP, 186 days
• Nonabuse: INVEGA SUSTENNA, >450 days; oAP, 284 days

Arrest/incarceration was the most common reason for treatment failure in both the substance abuse (INVEGA SUSTENNA: 40.0% [52/130]; oAP: 40.3% [54/134]) and nonabuse (INVEGA SUSTENNA: 18.8% [18/96]; oAP: 34.5% [29/84]) cohorts with a higher incidence occurring in the substance abuse cohort.

The median time [95% CI] to first psychiatric hospitalization or arrest/incarceration was:

• Substance abuse cohort: oAP: 317 days [194, >450]; INVEGA SUSTENNA: 371 days [247, >450]
• Nonabuse cohort: oAP: 371 days [165, >450]; INVEGA SUSTENNA: >450 days

Safety

A summary of TEAEs occurring in ≥10% of patients (by preferred term) for both treatment cohorts can be found in the Table: Summary of TEAEs (ITT Analysis Set).

The overall % of patients experiencing a TEAE/≥1 serious TEAE per cohort and treatment group, respectively were:

• Substance Abuse: INVEGA SUSTENNA, 87.7%/18.5%; oAP, 83.6%/25.4%
• Nonabuse: INVEGA SUSTENNA, 84.4%/18.8%; oAP, 78.6%/22.6%

TEAEs leading to treatment discontinuation per cohort and treatment group:

• Substance Abuse: INVEGA SUSTENNA, 11.5%; oAP, 6.7%
• Nonabuse: INVEGA SUSTENNA, 13.5%; oAP, 11.9%

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 13 September 2024.