Long-acting Injectable Therapy Research Articles

Virological History Predicts Non-sustained Viral Suppression With Long-Acting Cabotegravir and Rilpivirine Therapy, Independent of Pharmacokinetic Parameters

Abstract Background This study aimed to investigate factors contributing to non-sustained viral suppression, including intermittent viremia and persistent low-level viremia, during cabotegravir (CAB) plus rilpivirine (RPV) long-acting (LA) injectable therapy, with a focus on pharmacokinetics (PK). Methods A prospective cohort study was conducted on people with human immunodeficiency virus (HIV, PWH) transitioning from stable oral antiretroviral therapy (ART) to bimonthly CAB + RPV LA. Standardized follow-up included close monitoring through blood sampling for plasma human immunodeficiency virus type 1 (HIV-1) viral load (VL) and multiple plasma drug concentrations measurements to analyze the connection between PK parameters and virologic outcomes. Results Among 173 patients with a median (interquartile range [IQR]) follow-up of 11.1(7.1–13.2) months and 789 pre-dose measurements, 38.7% experienced VL ≥ 20 copies/mL, and 16.2% had levels ≥50 copies/mL. Intermittent viremia occurred in 34.7% of patients, and persistent low-level viremia in 4%. Virological failure developed in 2 cases. Predictors of non-sustained viral suppression included VL at HIV diagnosis (adjusted hazard ratio [AHR]: 1.49 per log10 VL, 95% confidence interval [CI]: 1.04–2.12, P = .027), detectable viremia on oral ART (AHR: 2.45, 95% CI: 1.29–4.65, P = .006), and the level of viral suppression at transition (AHR: 0.38, 95% CI: .19–.75, P = .004). We found a significant association between low trough concentrations of CAB and RPV and episodes of detectable viremia exceeding 50 copies/mL. However, none of the assessed PK covariates predicted non-sustained viral suppression in multivariable models. Conclusions Non-sustained viral suppression in PWH transitioning from stable oral ART to CAB + RPV LA was linked to preexisting factors before transition. Higher VL pre-ART and incomplete suppression on oral therapy increased the risk, independent of PK parameters.

Advancements in Long-Acting Injectable Therapies: Revolutionizing Cancer Treatment

This review aims to explore the advancements in long-acting injectable therapies [LAI] that are revolutionizing cancer treatment. With cancer posing a significant global health challenge, conventional treatments often come with limitations, including harmful side effects and resistance development. Long-acting formulations (LAFs), particularly those manipulating medication release through delivery systems, present a promising alternative. The review delves into various LAF approaches, such as micro-encapsulation, liposomes, oil-based LAPFs, nanocrystal suspensions, longacting hydrogels, microneedles, and implantable systems. These approaches offer sustained release, reduced toxicity, and improved therapeutic efficacy. The review highlights the benefits and disadvantages of LAIs, emphasizing improved adherence, reduced risk of relapse, and enhanced quality of life. Evaluation parameters, including pharmacokinetics, biocompatibility, stability, mechanical properties, and safety, are discussed. The comprehensive assessment underscores the ongoing efforts in oncological research to develop innovative and effective therapies that address the challenges associated with conventional cancer treatments.

Real-world effectiveness of long-acting injectable vs. oral antipsychotics in patients with bipolar I disorder: a 1-year retrospective observational study

Objective Long-acting injectable (LAI) antipsychotics are recommended in the treatment non-adherence. Despite the widespread use of LAI antipsychotics, there is limited data on clinical outcomes in bipolar I disorder (BD-I) patients with real-world data. We aimed to compare BD-I patients treated with LAI and oral antipsychotics (OAP) in terms of treatment effectiveness in a 1-year follow-up period. Methods The study was conducted retrospectively with electronic health records of 116 BDI patients. The primary outcomes were whether patients in the LAI group and the OAP group differed in relapse, rehospitalization, emergency room (ER) visits, and all-cause treatment discontinuation at 1-year follow-up after a mania episode. Cox regression modeling was used to predict the recurrence of any mood episode and all-cause treatment discontinuation during follow-up. The secondary outcomes evaluated were the effects of sociodemographic and clinical parameters and concomitant psychotropic medications on the course of the illness and treatment adherence. Results Of all 116 patients, 33 (28.4%) were under LAI, and 83 (71.6%) were under OAP treatment. LAI users had a history of more hospitalizations and total mood episodes. Patients in the LAI group had more treatment non-adherence before the index hospitalization. At 1-year follow-up, there was no difference between the groups in terms of any mood relapse, rehospitalization, ER visits, and all-cause treatment discontinuation. As a secondary outcome, lithium users were found to have fewer new episodes and discontinuations of treatments. Conclusions In real-world data, there is no evidence that LAI antipsychotics (compared to OAP) are superior in the maintenance treatment of BD. These results are important in terms of reflecting clinical practices for the treatment of BD-I. These results do not devalue the use of LAI therapy in BD; however, more studies are needed to identify positive predictors for LAI treatments in BD.

The role of long-acting antipsychotics in illness relapse: an observational study

IntroductionIn patients affected by Schizophrenia and Bipolar Disorder disorders the use of antipsychotic drugs is essential in preventing the exacerbation of symptoms. The use of long-acting injectable (LAI) antipsychotics is considered an important treatment option. The aim of this study was to evaluate the incidence and predictors of relapse during antipsychotic treatment with LAIs in a sample of psychiatric outpatients up to a year after the start of long-acting therapy.ObjectivesThe study included 103 adult patients admitted to the psychiatric unit of Sant’Andrea University Hospital in Rome.MethodsWe evaluated duration of untreated illness, previous treatments, substance abuse, suicidal status, LAI dose, and use of other medicines for association with new episodes of illness or of symptomatic worsening as well as hospitalization, using bivariate and multivariate analyses.Results Seventy-three patients were diagnosed with schizophrenia spectrum and 30 with bipolar disorders. Age at study entry averaged 36.7 years (SD= 11.55). 40.8% of patients were women. The mean age at onset were 23.11 (SD= 7.0). All the other information were reported in Table 1. On 103 patients undergoing with LAI treatment for a year only 9 (8.7%) patients had a relapse during the study period. The two groups differed according to the presence of hospitalization during the 12 months before the LAI treatment (p = .022), in particular patients with relapse were more hospitalized than patients with no relapse (62.5% vs. 21.7%). Moreover, group with relapse were more at risk of suicide during the 12 months before the LAI treatment than the other group, for both suicidal ideation (11.1% vs. 4.3%; p= .015) and attempt (25.0% vs. 3.2%; p= .049). Finally, the two groups differed according to the side effects reported during the year of LAI treatment (χ² =38.48; p< .001). Specifically, patients’ group with relapse reported more side effects caused by parkinsonism (25.0% vs. 1.1%) and tremor (25.0% vs. 0%). No differences were found for the other variables (See table 1).Image:ConclusionsIn conclusion, our observations confirm the importance of LAI therapy in real word. However, our results indicate that these drugs might not prevent subsequent exacerbations for a proportion of individuals whose illness is stabilised on continuous antipsychotic treatment. Extra pyramidal symptoms in particular might have pathophysiological implications for relapse.Disclosure of InterestNone Declared

Rilpivirine and cabotegravir trough concentrations in people with HIV on long-term treatment with long-acting injectable antiretrovirals.

Large inter-individual variability in the pharmacokinetics of rilpivirine and cabotegravir has been reported in the first weeks after starting long-acting injectable (LAI) therapy. Here, we assessed the distribution of rilpivirine and cabotegravir trough concentrations in people with HIV (PWH) on long-term LAI treatment. Adult PWH treated with LAI for at least 32 weeks with an assessment of drug plasma trough concentrations were considered. The proportion of rilpivirine and cabotegravir plasma trough concentrations below four-times the protein-adjusted concentrations required for 90% inhibition of viral replication (4×PA-IC90) was estimated. Sixty-seven PWH were identified. LAI treatment duration was 216 ± 80 weeks (range 32-320 weeks). Cabotegravir concentrations were associated with lower inter-individual variability compared with rilpivirine (45% versus 84%; P < 0.05). No differences were found in rilpivirine (160 ± 118 versus 189 ± 81 ng/mL; P = 0.430) and cabotegravir (1758 ± 807 versus 1969 ± 802 ng/mL; P = 0.416) trough concentrations in males (n = 55) versus females (n = 12). A non-significant trend for lower cabotegravir concentrations was found in PWH with a body mass index >30 kg/m2 (n = 9) versus non-obese participants (1916 ± 905 versus 1606 ± 576 ng/mL; P = 0.131). Three out of the 67 PWH had at least one drug concentration <4×PA-IC90: 100% of PWH had undetectable HIV viral load. At steady state, optimal systemic exposure of cabotegravir and rilpivirine was found in most PWH; cabotegravir trough concentrations were associated with lower inter-individual variability compared with rilpivirine. The study was not powered to assess the contribution of sex and/or body weight on LAI exposure due to the small number of females and obese PWH included.

Virological Failure After Switch to Long-Acting Cabotegravir and Rilpivirine Injectable Therapy: An In-depth Analysis.

Long-acting (LA) injectable therapy with cabotegravir (CAB) and rilpivirine (RPV) is currently used as maintenance treatment for human immunodeficiency virus type 1, and has a low risk for virological failure (VF). Although the risk is low, the circumstances and impact of VF in the real-world setting merit further evaluation. We performed an in-depth clinical, virological, and pharmacokinetic analysis on the reasons behind and the impact of VF during LA CAB/RPV therapy in 5 cases from the Netherlands. Genotypic resistance testing was performed after the occurrence of VF, and drug plasma (trough) concentrations were measured after VF was established and on any other samples to assess on-treatment drug levels. CAB and RPV drug levels that were below the first quartile of the population cutoff (≤Q1) were considered to be low. Five cases who were eligible for LA CAB/RPV experienced VF despite a low predicted risk at baseline. Genotypic resistance testing revealed extensive selection of nonnucleoside reverse transcriptase inhibitor-associated mutations in all cases, and integrase strand transfer inhibitor mutations in 4 cases. All cases displayed low drug levels of either CAB, RPV, or both during the treatment course, likely contributing to the occurrence of VF. In 3 cases, we were able to identify the potential mechanisms behind these low drug levels. This is the first in-depth multiple case analysis of VF on LA CAB/RPV therapy in a real-world setting. Our observations stress the need to be aware for (evolving) risk factors and the yield of a comprehensive clinical, virological, and pharmacokinetic approach in case of failure.

Development, validation and clinical implementation of a UPLC-MS/MS bioanalytical method for simultaneous quantification of cabotegravir and rilpivirine E-isomer in human plasma

A reversed phase ultra-high performance liquid chromatography method was developed for the simultaneous quantification of cabotegravir (CAB) and the E-isomer of rilpivirine (RPV) in human EDTA plasma, also considering RPV E-isomer instability. Because of the instability of RPV (and CAB) in all light conditions, the (RPV Z-isomer/total RPV)-isomer ratio of RPV was determined for each stock, calibration curve standard, quality control sample and patient sample. [2H3]-CAB and [13C6]-RPV were used as internal standard. Sample preparation involved protein precipitation of plasma using methanol. An HSS T3 column with a guard column (set at 40 °C) was used for analyte separation. The mobile phase components were 65 % 0.1 % formic acid in water (A) and 35 % 0.1 % formic acid in acetonitrile (B) and the flow rate was 0.5 mL/min. Detection was performed with tandem mass spectrometry (MS/MS) in a total runtime of 3.0 min. The assay was validated over the concentration range of 0.0500 – 10.0 mg/L for CAB and 0.00300 – 3.00 mg/L for RPV. The average within-day and between-day accuracies for the assay in plasma were 101 % and 101 % for CAB and 97.6 % and 98.5 % voor RPV, respectively. Within-day and between-day precision in coefficients of variations (CV) were 5.0 %. Extraction recovery was 99 % and 102 % for CAB and its internal standard and 95 % and 97 % for RPV and its internal standard. As our aim was that the (Z-isomer RPV/total RPV) response ratio in patient samples had to be less than 10 % to give reliable results, the (Z-isomer RPV/total RPV) response ratio in stocks, calibration curve standards and internal quality control samples were also taken into account being maximal 0.9 % and 2.3 % respectively. This assay has been successfully used in our Therapeutic Drug Monitoring (TDM) service for people living with HIV on long-acting injectable therapy with CAB/RPV and will also be used in future pharmacokinetic studies.

Comparison of health resource usage and costs associated with first-generation and second-generation long-acting injectable antipsychotics for patients with schizophrenia: A nationwide population-based cohort study.

The aim of this study was to examine psychiatric resource utilization, medical costs and clinical outcomes for patients with schizophrenia who received either first-generation or second-generation long-acting injectable (LAI) antipsychotics. A retrospective cohort study was conducted using data from Taiwan's National Health Insurance Research Database (NHIRD). Patients who began either first-generation or second-generation LAI treatment between 2015 and 2017 were enrolled and followed for three years. The data were evaluated using survival analysis and Cox proportional hazards regression models. Our findings demonstrated that both first- and second-generation LAI therapies led to notable reductions in the frequency of psychiatric hospitalizations and the duration of hospital stays when compared to the initial measurements. Additionally, the second-generation LAI group exhibited significantly lower rates of psychiatric emergencies and hospitalizations, as well as shorter hospital stays, compared to the first-generation LAI group. However, it is worth noting that the second-generation LAI group incurred higher pharmacy fees despite these favorable outcomes. The utilization of both first- and second-generation LAIs can enhance medication adherence and decrease the risk of acute exacerbation in patients with schizophrenia. These findings hold significant implications for schizophrenia management and the efficient allocation of healthcare resources.

Criminal behaviors and substance abuse in psychiatric patients

IntroductionPeople with mental illness are overrepresented throughout the criminal justice system. In Italy, an ongoing process of deinstitutionalization has been enacted: the Judicial Psychiatric Hospitals are now on the edge of their closure in favor of small-scale therapeutic facilities (Residenze per l’Esecuzione delle Misure di Sicurezza - REMS). Law 81/2014 prescribes that a patient cannot stay in a REMS for a period longer than a prison sentence for the same index offense. Therefore, when patients end their duty for criminal behaviors, their clinical management moves back to outpatient psychiatric centers. Elevated risks of violent behavior are not equally shared across the spectrum of psychiatric disorders. In the past several years, multiple studies in the field of forensic psychiatry confirmed a close relationship between violent offenders and comorbid substance abuse.ObjectivesIn order to broaden the research in this area, we analyzed sociodemographic, clinical and forensic variables of a group of psychiatric patients with a history of criminal behaviors, attending an outpatient psychiatric service in Milan, with a focus on substance abuse.MethodsThis is a cross-sectional single center study, conducted in 2020. Seventy-six subjects with a history of criminal behaviors aged 18 years or more and attending an outpatient psychiatric service were included. Demographic and clinical variables collected during clinical interviews with patients were retrospectively retrieved from patients’ medical records. Appropriate statistical analyses for categorical and continuous variables were conducted.ResultsData were available for 76 patients, 51,3% of them had lifetime substance abuse. Lifetime substance abuse was significantly more common in patients with long-acting injectable antipsychotics therapy, &gt;3 psychiatric hospitalizations, history of previous crimes and economic crime (Table 1). Additionally, this last potential correlation was confirmed by logistic regression.Table 1.Lifetime substance abusers (N=39)Non-lifetime substance abusers (N=37)Proportion DifferenceP-valueN%N%Depot administrationYes11(28,9%)0(0%)28,9%0,02HospitalizationsFour or more25(64,1%)5(33,3%)30,8%0,04Economic crimeYes15(40,5%)1(6,7%)33,8%0,02Previous crimesYes17(51,4%)2(13,3%)38,1%0,02ConclusionsData emerging from this survey provide new information about offenders in an Italian mental health service with a focus on lifetime substance abuse in these patients. Our preliminary results should be confirmed in larger sample sizes.Disclosure of InterestNone Declared

Practical dosing guidance for the management of clinician-administered injections of long-acting cabotegravir and rilpivirine.

Cabotegravir (CAB) and rilpivirine (RPV) is the first complete long-acting (LA) injectable regimen recommended by treatment guidelines for the maintenance of HIV-1 virologic suppression in people with HIV-1 who are virologically suppressed on a stable antiretroviral regimen that is administered monthly (Q1M) or every 2 months (Q2M). As an alternative regimen to lifelong daily oral antiretroviral therapy, Q1M or Q2M dosing schedules are associated with increased patient satisfaction and treatment preference. In addition, it may address challenges associated with daily oral dosing, including fear of treatment disclosure or stigma, anxiety related to oral dosing adherence, and the daily reminder of HIV disease status. Cabotegravir + RPV LA is administered by clinical staff as two intramuscular injections dosed Q1M or Q2M. In this review, we share practical dosing guidance for CAB+RPV LA injectable therapy, including how to initiate therapy, schedule injection visits, manage dosing interruptions due to missed or delayed injection visits, manage errors in dosing, and transition to alternative antiretroviral therapy after discontinuation. Practical guidance on the clinical management of CAB+RPV LA dosing, including a detailed discussion using case-based scenarios that may be encountered in clinical practice, is provided. The clinician-administered CAB+RPV LA regimen has dosing management considerations that are flexible and considerate of the patient and has the potential to provide a highly desirable and efficacious alternative to daily oral antiretroviral therapy for many people with HIV-1.

PCR162 Patient and Physician Perspectives Towards Current HIV Treatment Satisfaction and the Use of Long-Acting Injectable Therapy for HIV in Taiwan

PCR162 Patient and Physician Perspectives Towards Current HIV Treatment Satisfaction and the Use of Long-Acting Injectable Therapy for HIV in Taiwan

Realizing the promise of long-acting antiretroviral treatment strategies for individuals with HIV and adherence challenges: an illustrative case series

BackgroundAdherence to antiretroviral treatment (ART) remains the cornerstone of optimal HIV outcomes, including viral suppression (VS), immune recovery, and decreased transmission risk. For many people with HIV (PWH), particularly those with early-acquired HIV, structural, behavioral, and cognitive barriers to adherence and competing priorities related to life events may be difficult to overcome, resulting in nonadherence. Long-acting injectable antiretroviral therapies (LAI-ART) may be a useful strategy to overcome some of these barriers. However, to date, the approved LAI-ART strategies (e.g., cabotegravir and rilpivirine (CAB/RPV)) have targeted those who have already attained viral suppression, precluding their use in the 40% of adolescents and young adults (AYA) that VS has eluded.Case presentationMs. X is a 30-year-old woman with perinatally-acquired HIV and barriers to adherence. Despite many interventions, she remained persistently viremic, with resultant immune suppression and multiple comorbid opportunistic conditions, and viral load (VL) > 10,000,000 copies/ml. Given her longstanding history of poor adherence to an oral regimen, a switch to monthly intramuscular (IM) injections and biweekly infusions of ibalizumab were initiated leading to decreased viral load to 8,110 copies/ml within two weeks. Ms. H is a 33-year-old woman with cognitive limitations due to childhood lead poisoning. Her viral load trajectory took a downward turn, precipitated by various life events, remaining elevated despite intensive case management. Initiation of LAI-ART (CAB/RPV) in this patient led to an undetectable VL (< 20 copies/ml) within two months of treatment initiation. Miss Y. is a 37-year-old woman with perinatally-acquired HIV and chronic challenges with nonadherence and longstanding immunosuppression with CD4 < 200 cells/mm3 for > 5 years. She received a 1-month oral lead-in (OLI) of cabotegravir/rilpivirine, followed by the injectable loading dose. She has since adhered to all her monthly dosing appointments, sustained VS, and transitioned to a bi-monthly injection schedule.ConclusionThese three individuals with HIV (perinatally and non-perinatally acquired) with longstanding nonadherence and persistent viremia were successfully initiated on LAI-ART through the process of care coordination and the collective efforts of the care team, highlighting the barriers, challenges, and the multidisciplinary coordination needed to assure successful implementation of this strategy for the most vulnerable of patients.

Cabotegravir: The First Long-Acting Injectable for HIV Preexposure Prophylaxis.

Review the pharmacology, pharmacokinetics, efficacy, safety, and role of long-acting injectable cabotegravir (CAB-LA) in HIV preexposure prophylaxis (PrEP). A literature search was performed using PubMed and Google Scholar (2012 to April 2022) with the search terms cabotegravir, preexposure prophylaxis, and PrEP. Other resources included abstracts presented at recent conferences, the manufacturer's Web site, prescribing information, and review articles. All English-language articles of studies assessing the efficacy and safety of CAB-LA for PrEP were included. CAB-LA is the first long-acting injectable therapy approved for HIV-1 PrEP in both men and women. It is a suspension given intramuscularly every other month. CAB-LA has been shown to be more effective than daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in preventing HIV-1 infection among high-risk individuals. Two phase 3 trials were stopped early on the basis of superior efficacy of CAB-LA. The most common adverse effects were injection site reactions (ISRs), although they tended to decrease over time, and few participants in clinical trials discontinued use due to ISRs. CAB-LA may be particularly useful for individuals with known adherence problems to oral therapy, those with renal impairment, and those with decreased bone mineral density. However, CAB-LA is more expensive than generic TDF/FTC and may be associated with weight gain. CAB-LA is the first long-acting injectable agent for HIV PrEP. It is more effective than oral TDF/FTC, is well-tolerated aside from ISRs, and has few clinically significant drug-drug interactions.

Online Survey of Clinical Practice in Patients with Schizophrenia Treated with Long-Acting Injectable Aripiprazole or Paliperidone Palmitate.

BackgroundTo obtain real-world evidence of functional improvements during atypical long-acting injectable (aLAI) therapy in recent-onset schizophrenia, an online survey was conducted to assess the impact of aripiprazole once-monthly injectable 400 mg (AOM 400; partial D2 receptor agonist) and paliperidone palmitate once-monthly (PP1M; injectable, full D2 receptor antagonist).MethodsPsychiatrists provided data for their 2 most recent AOM 400 patients, 2 most recent PP1M patients. Survey included 2000 patient cases (1000 AOM 400; 1000 PP1M). Eligible patients were aged 18–35 years, had been diagnosed with schizophrenia within 5 years, received AOM 400 or PP1M continuously for ≥6 months according to approved labels (mean durations: 1.6 and 1.7 years with AOM 400 and PP1M, respectively). Assessments included Global Assessment of Functioning (GAF) Scale, Personal and Social Performance Scale, Positive and Negative Syndrome Scale, and Quality of Life Scale. GAF assessments were done retrospectively and also at the time of survey.ResultsBaseline mean GAF scores were 43.3 and 43.8 for AOM 400 and PP1M, respectively, indicating serious symptoms/functional impairment in both groups. Mean improvements following AOM 400 and PP1M therapy were 19.7 and 16.3 points, respectively (final scores in mild functional impairment category). Other measures assessing symptoms/functionality/quality of life demonstrated the benefits of long-term aLAI therapy.ConclusionSchizophrenia patients with serious functional impairment prior to current aLAI treatment showed improvements in functional outcome after AOM 400 or PP1M therapy. These results suggest functional improvements with aLAIs are apparent not only in research but also real-world settings.

Self- and caregiver-perceived disability, subjective well-being, quality of life and psychopathology improvement in long-acting antipsychotic treatments: a 2-year follow-up study

Objective Switching to long-acting injectable (LAI) antipsychotic maintenance treatment (AMT) represents a valuable strategy for schizophrenia. In a recovery-oriented approach, patient-reported outcomes (PROs) such as perceived disability, subjective well-being, and quality of life cannot be neglected. Methods Forty clinically stable outpatients with schizophrenia treated with oral second-generation antipsychotics were enrolled at the time of switching to the equivalent dose of LAI. 35 subjects completed this 2-year longitudinal, prospective, open-label, observational study. Patients were assessed at baseline, after 1 year, and after 2 years of LAI-AMT, using psychometric scales (Positive And Negative Syndrome Scale, PANSS; Young Mania Rating Scale, YMRS; Montgomery-Åsberg Depression Rating Scale, MADRS), PROs (Subjective Well-Being under Neuroleptics short form, SWN-K; Short Form-36 health survey, SF-36; 12-item World Health Organisation Disability Assessment Schedule, WHODAS 2.0), and caregiver-reported outcomes (12-item WHODAS 2.0). Results No psychotic relapses were observed. Psychopathology measures (PANSS total and subscales – excluding negative symptoms), mood symptoms (YMRS, MADRS), perceived disability (patient- and caregiver-administered WHODAS 2.0), subjective well-being (SWN-K), and quality of life (SF-36) showed a concomitant amelioration after 1 year, without further significant variations. Discussion Switching to LAI-AMT may decrease perceived impairment, and increase subjective well-being and quality of life in clinically stable outpatients with schizophrenia. Highlights LAI treatment may improve outcomes by reducing psychopathology levels and relapses. In a recovery-oriented approach, patient-reported outcomes cannot be neglected. LAI antipsychotics may optimise the subjective experience of treatment. Switching to LAI therapy may result in a reduction in perceived disability. There is a significant correlation between proxy- and patient-reported disability.

Long-acting injectable HIV therapies: the next frontier.

There has been significant development of long-acting injectable therapy for the management of HIV in recent years that has the potential to revolutionise HIV care as we know it. This review summarises the data and outlines the potential challenges in the field of long-acting antiretroviral therapy (ART). In recent years, monthly and two monthly long-acting injectable ART in the form of cabotegravir and rilpivirine has shown safety and efficacy in large-scale phase 3 randomised control trials. Also, agents with novel mechanisms of action, such as Lenacapavir, have been tested in early-phase studies and are currently being tested in phase 2-3 clinical trials; if successful, this may allow six-monthly dosing schedules. However, despite evidence that suggests that these therapies are efficacious and acceptable to patients, the challenge of integrating these agents into our current healthcare infrastructure and making these novel agents cost-effective and available to the populations most likely to benefit remains. The next frontier for long-acting therapy will be to introduce these agents in a real-world setting ensuring that the groups most in need of long-acting therapy are not left behind.

Long-acting injectable therapy: an emerging paradigm for the treatment of HIV infection.

Long-acting formulations of antiretrovirals have the potential to reshape the treatment paradigm for HIV infection. Emerging evidence demonstrates efficacy and safety of two drug regimens for the treatment of HIV infection. This review focuses on recent advances with long-acting cabotegravir and rilpivirine administered intramuscularly every 4 weeks for the treatment of HIV infection in virologically suppressed patients. Despite the development of complete, orally administered single tablet regimens with improved efficacy, side effects, tolerability, with an improved drug interaction potential, patients still have challenges adhering to daily oral therapy. Psychological factors including HIV stigma contribute to patient's ability to adhere to treatment. Newer nonoral treatment regimens may improve adherence, patient satisfaction and limit HIV stigma. A two-drug intramuscular regimen of cabotegravir and rilpivirine has advanced through phase 3 clinical development. Results from studies assessing safety, virologic, pharmacologic, and drug interactions have been completed. Larger efficacy studies have demonstrated noninferiority of switching virologically suppressed patients from a three drug daily oral regimen to a two-drug intramuscular regimen administered Q4W with long-term data to 160 weeks demonstrating durability of treatment response.

The prospective economic impact of once monthly paliperidone palmitate versus oral atypical antipsychotics in Medicaid patients with schizophrenia

Objectives: Multiple real-world studies have reported potential cost savings associated with second-generation antipsychotic long-acting injectable therapies (SGA-LAIs), including once monthly paliperidone palmitate (PP1M). Yet, only about 12% of Medicaid patients with schizophrenia initiate SGA-LAIs, with poor adherence contributing to frequent relapse among patients on oral atypical antipsychotics (OAAs). The objective of this study was to project the economic impact when an incremental proportion of non-adherent patients with a recent relapse switched from OAAs to PP1M.Methods: A 12 month decision-tree model was developed from a Medicaid payers’ perspective. The target population was non-adherent OAA patients with a recent relapse. At equal adherence, risk of relapse was equal between PP1M and OAAs, and OAA patients remained non-adherent until treatment switch. Outcomes included number of relapses, relapse costs and pharmacy costs.Results: Based on a hypothetical health plan of 1 million members, 3037 schizophrenia patients were non-adherent on OAAs with a recent relapse. Compared to continuing OAAs, switching 5% of patients (n = 152) to PP1M resulted in net schizophrenia-related cost savings of $674,975 at a plan level, $4445 per patient switched per year and $0.0562 per member per month, with a total of 92 avoided relapses over 12 months. Total annual plan level schizophrenia-related costs were $114.1 M when all patients switched to PP1M before any subsequent relapse (n = 3037), $123.4 M when patients switched to PP1M after a first subsequent relapse (n = 2631), and $127.6 M when all patients continued OAAs. Switching all patients to PP1M before any subsequent relapse averted 917 relapses, at a lower cost per patient switched ($37,559) compared to switching after a first subsequent relapse ($45,089) or continuing OAAs ($42,005).Conclusion: Over 12 months, pharmacy costs associated with switching patients from OAAs to PP1M were offset by reduced relapse rates and schizophrenia-related healthcare expenditures, with earlier use of PP1M projected to generate greater cost savings.

Treatment patterns and Medicaid spending in comorbid schizophrenia populations: once-monthly paliperidone palmitate versus oral atypical antipsychotics

Objective: To compare treatment patterns and Medicaid spending between schizophrenia patients initiating once-monthly paliperidone palmitate (PP1M) and oral atypical antipsychotics (OAAs) within four comorbid populations: cardiovascular disease (CVD), diabetes, hypertension and obesity.Methods: Five-state Medicaid data identified comorbid adults with schizophrenia initiating PP1M or OAAs (index) from September 2009 balanced with inverse probability of treatment weighting. Chi-squared and t-tests compared index antipsychotic (AP) exposure (no gap >90 days) duration, AP polypharmacy, and index AP adherence (proportion of days covered ≥80%) and persistence (no gap ≥60 days) at 12 months post-index. Linear models with a non-parametric bootstrap procedure compared costs.Results: PP1M patients consistently had longer index AP exposure (e.g. CVD: 244 vs. 189 days; p < .001) and less AP polypharmacy (e.g. CVD: 21.1% vs. 28.1%; p < .001) versus OAA patients. Relative to OAA patients, adherence was more likely in PP1M patients with CVD or obesity (e.g. CVD: 28.6% vs. 22.1%; p < .001) and less likely for patients with diabetes (22.0% vs. 24.4%; p = .031). Persistence was consistently more likely for PP1M versus OAA patients (e.g. CVD: 49.9% vs. 27.4%; p < .001). Total costs were not significantly different between PP1M and OAA patients for any comorbidity. PP1M patients with diabetes, hypertension or obesity had higher pharmacy and lower medical costs (all p < .05).Conclusions: Treatment with PP1M versus OAAs may reduce AP polypharmacy and increase AP persistence in comorbid patients with schizophrenia, without increasing total healthcare costs. Comorbidities are a highly prevalent driver of excess mortality in this vulnerable population; thus, future studies should specifically address the real-world effectiveness of therapies, including long acting injectable therapies (LAIs), for these patients.

Treatment Patterns, Health Care Resource Utilization, and Spending in Medicaid Beneficiaries Initiating Second-generation Long-acting Injectable Agents Versus Oral Atypical Antipsychotics

PurposeSecond-generation long-acting injectable therapies (SGA-LAIs) may reduce health care resource utilization (HRU) and health care costs compared with daily oral atypical antipsychotics (OAAs) in patients with schizophrenia due to reduced dosing frequency, delivery/monitoring by a health care provider, and improved adherence. The aim of the present study was to compare treatment patterns, HRU, and Medicaid spending in patients with schizophrenia initiated on SGA-LAIs (overall and according to agent) versus OAAs. MethodsMedicaid claims data (2010–2015) from 6 states were used to identify adult schizophrenia patients initiated on SGA-LAIs or OAAs. Treatment patterns (proportion of days covered [PDC] ≥80% and persistence [no gap ≥30, 60, or 90 days] to index treatment), HRU, and costs were evaluated over 12 months and compared by using multivariable logistic, Poisson, and ordinary least squares regression models, respectively. P values for HRU and cost outcomes were obtained from a nonparametric bootstrap procedure. Costs (2015 US dollars) reflect the Medicaid payer’s perspective before any rebate. FindingsOverall, 3307 and 21,355 patients initiated SGA-LAIs and OAAs, respectively (paliperidone palmitate LAI [PP-LAI; n = 2182], risperidone LAI [n = 968], aripiprazole LAI [n = 108], and olanzapine LAI [n = 49]). During follow-up and compared with OAA patients, SGA-LAI patients were more likely to reach PDC ≥80% (odds ratio [OR], 1.28; P < 0.001) and be persistent (eg, no gap ≥60 days; OR, 1.45; P < 0.001) to the index treatment. Relative to OAA patients, SGA-LAI patients had fewer long-term care days (incidence rate ratio [IRR], 0.75; P < 0.001) and home care visits (IRR, 0.75; P < 0.001) but more mental health institute (IRR, 1.16; P < 0.001) and 1-day mental health institute (IRR, 1.16; P < 0.001) admissions. Moreover, PP-LAI patients had fewer inpatient days (IRR, 0.78; P = 0.004) versus OAA patients. SGA-LAI patients had lower medical costs (mean monthly cost difference [MMCD], –$168; P < 0.001) than OAA patients, offsetting more than one half of the higher pharmacy costs (MMCD, $271; P < 0.001). Compared with OAAs, only PP-LAI was associated with significant medical cost savings (MMCD, –$225; P < 0.001). ImplicationsMedicaid beneficiaries with schizophrenia initiated on SGA-LAIs had better adherence and persistence to therapy over 12 months than patients initiated on OAAs. SGA-LAIs, particularly PP-LAI, were associated with lower medical costs that successfully offset more than one half of the higher pharmacy costs relative to OAA.