Tracking of Systemic Lupus Erythematosus (SLE) Longitudinally Using Biosensor and Patient-Reported Data: A Report on the Fully Decentralized Mobile Study to Measure and Predict Lupus Disease Activity Using Digital Signals-The OASIS Study.

(1) Objective: Systemic lupus erythematosus (SLE) is a complex disease involving immune dysregulation, episodic flares, and poor quality of life (QOL). For a decentralized digital study of SLE patients, machine learning was used to assess patient-reported outcomes (PROs), QOL, and biometric data for predicting possible disease flares. (2) Methods: Participants were recruited from the LupusCorner online community. Adults self-reporting an SLE diagnosis were consented and given a mobile application to record patient profile (PP), PRO, and QOL metrics, and enlisted participants received smartwatches for digital biometric monitoring. The resulting data were profiled using feature selection and classification algorithms. (3) Results: 550 participants completed digital surveys, 144 (26%) agreed to wear smartwatches, and medical records (MRs) were obtained for 68. Mining of PP, PRO, QOL, and biometric data yielded a 26-feature model for classifying participants according to MR-identified disease flare risk. ROC curves significantly distinguished true from false positives (ten-fold cross-validation: p < 0.00023; five-fold: p < 0.00022). A 25-feature Bayesian model enabled time-variant prediction of participant-reported possible flares (P(true) > 0.85, p < 0.001; P(nonflare) > 0.83, p < 0.0001). (4) Conclusions: Regular profiling of patient well-being and biometric activity may support proactive screening for circumstances warranting clinical assessment.

Continued Posttrial Benefits of Buprenorphine Extended Release: RECOVER Study Findings.

BACKGROUND: This analysis describes participants' opioid use disorder (OUD) outcomes for 18 months after discontinuing extended-release buprenorphine injection (BUP-XR, SUBLOCADE). METHODS: The RECOVER (Remission From Chronic Opioid Use: Studying Environmental and Socioeconomic Factors on Recovery) study recruited participants from BUP-XR clinical trials (NCT02357901, NCT025100142, and NCT02896296) to assess whether there were sustained benefits after leaving the trial. Abstinence from opioids and from all illicit substances (excluding medical cannabis), health-related quality of life, depression, and employment were measured after BUP-XR discontinuation and change in outcomes assessed at 6, 12, and 18 months. Results were analyzed within the full cohort and by duration of BUP-XR treatment (0-2 months, 3-5 months, 6-11 months, 12 months, or 13-18 months) with and without inverse probability weights adjusting for differences in baseline characteristics. RESULTS: Of 533 participants, 529 were assessed over the 18-month study period. Further posttrial pharmacotherapy was reported by 33% of participants. At RECOVER baseline, longer BUP-XR was associated with higher abstinence (0-2 months BUP-XR [n = 116]: 38.8%; 3-5 months BUP-XR [n = 61]: 41.0%; 6-11 months BUP-XR [n = 86]: 68.6%; 12 months BUP-XR [n = 135]: 71.9%; 18 months BUP-XR [n = 131]: 88.2%) and greater 12-Item Short Form Health Survey mental component scores. Over 60% of participants had stable or improved outcomes at 6, 12, and 18 months assessments. Overall 47% of participants self-reported sustained opioid abstinence for the full 18-month follow-up, with greater sustained abstinence associated with longer BUP-XR treatment duration. A sensitivity analysis, removing patients receiving medications for OUD, yielded similar results. CONCLUSIONS: Participants from BUP-XR clinical trials who continued into RECOVER maintained or improved on numerous outcomes over 18 months, demonstrating the long-term positive impact of OUD pharmacotherapy.

Social determinants of health in pulmonary arterial hypertension patients in the United States: Clinician perspective and health policy implications.

Social determinants of health (SDoH) can impact the vulnerable pulmonary arterial hypertension (PAH) population, especially during the COVID-19 pandemic. Providers' understanding of SDoH at the point of care and their impact is unknown. We conducted semi-structured virtual interviews with US clinicians at 17 pulmonary hypertension (PH) centers and one patient advocate from the Pulmonary Hypertension Association. We sought participants' perspective on SDoH in PAH and their impact. Transcripts were developed and analyzed for key themes to assess potential policy implications. Participants served a large PAH population and demonstrated high awareness of SDoH and its impact on treatment and outcomes. They reported that patients' SDoH, including socioeconomic status, health insurance, access to health care, education levels, health literacy, employment status, and insecurities associated with housing, food, transportation, and family support, impacted health and well-being. COVID-19-related social isolation, mental health, and substance abuse contributed to significant inequities in care provision and outcomes. While telemedicine helped clinicians manage patients remotely during the pandemic, there was a concern for patients with limited access to this medium. Participants reported no formal screening for SDoH at the point of care. With the recognition and the desire to act upon health inequities associated with SDoH, participants felt that it was vital for their centers to have a dedicated PH social worker and support staff to optimize care and outcomes. An approach that integrates SDoH in PAH care management, streamlined through institutional policy, could address health disparities leading to improved healthcare access, outcomes, and quality of care.

Real-world treatment patterns, healthcare resource utilization, and cost among adults with pulmonary arterial hypertension in the United States.

Treatment for pulmonary arterial hypertension (PAH) has evolved over the past decade, including approval of new medications and growing evidence to support earlier use of combination therapy. Despite these changes, few studies have assessed real-world treatment patterns, healthcare resource utilization (HCRU), and costs among people with PAH using recent data. We conducted a retrospective cohort study using administrative claims from the HealthCore Integrated Research Database®. Adult members with claims for a PAH diagnosis, right heart catheterization, and who initiated PAH treatment (index date) between October 1, 2015 and November 30, 2020 were identified. Members had to be continuously enrolled in the health plan for 6 months before the index date (baseline) and ≥30 days after. Treatment patterns, HCRU, and costs were described. A total of 843 members with PAH (mean age 62.3 years, 64.2% female) were included. Only 21.0% of members received combination therapy as their first-line treatment, while most members (54.6%) received combination therapy as second-line treatment. All-cause HCRU remained high after treatment initiation with 58.0% of members having ≥1 hospitalization and 41.3% with ≥1 emergency room visit. Total all-cause costs declined from $15,117 per patient per month at baseline to $14,201 after treatment initiation, with decreased medical costs ($14,208 vs. $6,349) more than offsetting increased pharmacy costs ($909 vs. $7,852). In summary, despite growing evidence supporting combination therapy, most members with PAH initiated treatment with monotherapy. Total costs decreased following treatment, driven by a reduction in medical costs even with increases in pharmacy costs.

Treating Opioid Use Disorder With a Monthly Subcutaneous Buprenorphine Depot Injection: 12-Month Safety, Tolerability, and Efficacy Analysis.

BACKGROUND: BUP-XR (RBP-6000 or SUBLOCADE) is the first Food and Drug Administration-approved subcutaneously administered monthly extended-release buprenorphine medication for the treatment of moderate or severe opioid use disorder. The primary objective of this phase III study was to assess the long-term safety, tolerability, and efficacy of BUP-XR. METHODS: This open-label multicenter study in adults with moderate or severe opioid use disorder enrolled 257 participants from a previously conducted placebo-controlled, double-blind phase III study (rollover group) and 412 de novo participants not previously treated with BUP-XR. Participants received an initial injection of BUP-XR 300 mg and subsequent monthly 300 mg or 100 mg flexible doses. By study end, participants received up to 12 injections. RESULTS: Overall, 66.8% of participants reported more than 1 treatment-emergent adverse event (TEAE). Injection-site TEAEs (13.2% of participants) were mostly mild or moderate in severity. There were no clinically meaningful changes in safety assessments. An integrated analysis of the double-blind and open-label study participants showed that the incidence of TEAEs, including injection-site TEAEs, was lower in the second 6 months of treatment versus the first 6 months. After 12 months of treatment, 61.5% of the rollover participants and 75.8% of the de novo participants were abstinent. Retention rates after 12 months were 50.6% for the participants who initiated BUP-XR in the double-blind study and 50.5% for de novo participants. CONCLUSIONS: This study demonstrates that the clinical benefits and acceptable safety profile of BUP-XR demonstrated in the 6-month double-blind study are sustained over a 12-month open-label study, with lower incidence of TEAEs in the second 6 months of treatment.

Recovery From Opioid Use Disorder (OUD) After Monthly Long-acting Buprenorphine Treatment: 12-Month Longitudinal Outcomes From RECOVER, an Observational Study.

OBJECTIVES: While evidence has mounted regarding the short-term effectiveness of pharmacotherapy for opioid use disorder (OUD), little is known about longer-term psychosocial, economic, and health outcomes. We report herein 12-month outcomes for an observational study enrolling participants who had previously taken part in a long-acting buprenorphine subcutaneous injection (BUP-XR) trial for moderate to severe OUD. METHODS: The RECOVER (Remission from Chronic Opioid Use: Studying Environmental and SocioEconomic Factors on Recovery; NCT03604861) study enrolled participants from 35 US community-based sites. Self-reported sustained opioid abstinence over 12 months and self-reported past-week abstinence at 3-, 6-, 9-, and 12-month visits were assessed. Multiple regression models assessed the association of BUP-XR duration with abstinence, controlling for potential confounders. Withdrawal, pain, health-related quality of life, depression, and employment at RECOVER baseline and 12-month visits were also compared to values collected before treatment in the BUP-XR trial. RESULTS: Of 533 RECOVER participants, 425 completed the 12-month visit (average age 42 years; 66% male); 50.8% self-reported sustained 12-month and 68.0% past-week opioid abstinence. In multiple regressions, participants receiving 12-month versus ≤2-month BUP-XR treatment duration had significantly higher likelihood of sustained opioid abstinence (75.3% vs 24.1%; P = 0.001), with similar results for past-week self-reported abstinence over time. During RECOVER, participants had fewer withdrawal symptoms, lower pain, positive health-related quality of life, minimal depression, and higher employment versus pre-trial visit. CONCLUSIONS: RECOVER participants reported positive outcomes over the 12-month observational period, including high opioid abstinence and stable or improved humanistic outcomes. These findings provide insights into the long-term impact of pharmacotherapy in OUD recovery.

Effects of monthly buprenorphine extended-release injections on patient-centered outcomes: A long-term study.

INTRODUCTION: The physical, social, psychological, and economic burden of opioid use disorder (OUD) is substantial. As of the year 2019, the predominant focus of OUD research was outcomes such as retention and abstinence. We report herein the effects of extended-release buprenorphine (BUP-XR), the first FDA-approved subcutaneously injected, monthly treatment for OUD, on patient-centered outcomes. MATERIALS AND METHODS: Patient-centered outcomes were collected during an open-label safety study of participants with OUD (NCT# 02510014) evaluating BUP-XR. Measures collected during the study included the EQ-5D-5L, SF-36v2, Treatment Effectiveness Assessment (TEA), Addiction Severity Index-Lite (ASI-Lite), employment/insurance status questionnaire, and Medication Satisfaction Questionnaire (MSQ). Changes from baseline to end of study week 49 were analyzed using mixed models for repeated measures. "Baseline" was defined as the value collected prior to the first BUP-XR injection. Results presented are for those participants who initiated treatment on BUP-XR during the open-label study and were eligible to receive up to 12 injections. RESULTS: Four hundred twelve participants were included in analyses; 206 participants discontinued BUP-XR prematurely. Mean EQ-5D-5L scores remained stable from baseline to end of study. Statistically significant improvements from baseline to end of study were noted for the SF-36v2 mental component summary score (difference = 5.0, 95%CI: 3.5-6.5) and 7 of 8 domain scores (P < .05 for all comparisons); the SF-36v2 physical component summary remained stable from baseline to end of study. The TEA total score (difference = 9.3 points, 95%CI: 8.0-10.5) and 4 of 4 domain scores (difference = 2-3 points per domain) significantly improved from baseline to end of study. Significant improvements (P < .05 for all comparisons) on the ASI-Lite were seen for all problem areas except alcohol use from baseline to end of study. Employment rate increased 7% whereas health insurance status remained stable from baseline to end of study. Medication satisfaction measured using the MSQ was >88% at end of study. CONCLUSIONS: Treatment with BUP-XR monthly injections for up to 12 months in this cohort of treatment-seeking individuals with OUD led to positive PCOs and high treatment satisfaction, which correspond to personal recovery.

Patient-reported outcomes in schizophrenia patients treated with once-monthly extended-release risperidone in a long-term clinical study.

PURPOSE: RBP-7000 (PERSERIS™) is a once-monthly subcutaneous extended-release risperidone formulation approved by the United States Food and Drug Administration for the treatment of schizophrenia in adults. The objective of this study was to describe the long-term impact of RBP-7000 on health-related quality of life (HRQoL), subjective well-being, treatment satisfaction and medication preference in patients with schizophrenia. PATIENTS AND METHODS: HRQoL was derived from a 52-week multicentre Phase III single-arm open-label outpatient study that assessed the safety and efficacy of RBP-7000 (120 mg) in patients with schizophrenia. HRQoL was measured using the EuroQol EQ-5D-5L and Short-Form Survey SF-36 version 2; well-being using the Subjective Well-being Under Neuroleptic Treatment - Short Version (SWN-S); satisfaction using the Medication Satisfaction Questionnaire and medication preference using the Preference of Medication questionnaire. RESULTS: Of 482 participants at baseline, 234 remained through the end of study (EOS; week 52). Mean HRQoL and well-being scores remained stable between baseline (EQ-5D-5L index: 0.83; SF-36v2 Physical Component Score: 50; SF-36v2 Mental Component Score: 46; total SWN-S score: 89) and EOS (EQ-5D-5L index: 0.86; SF-36v2 Physical Component Score: 49; SF-36v2 Mental Component Score: 47; total SWN-S score: 90). The proportion of participants reporting satisfaction increased between week 4 (66%) and EOS (81%), with a similar trend for the preference of RBP-7000 over previous treatment (week 4: 66%; EOS: 72%). Sensitivity analyses suggested a minor effect of dropout on characterization of change over time in patient-reported outcomes (PRO) measures. CONCLUSION: Study participants attained mean HRQoL scores near that of the general US population. Over two-thirds reported high satisfaction with and preference for RBP-7000 across the study period. Additional research is needed to confirm whether these PRO translate into improved outcomes such as adherence and ultimately fewer relapses in patients with schizophrenia.

Measuring recovery in opioid use disorder: clinical utility and psychometric properties of the Treatment Effectiveness Assessment.

Purpose: The Treatment Effectiveness Assessment (TEA) is a patient-centered instrument for evaluating treatment progress and recovery from substance use disorders, including opioid use disorder (OUD). We assessed the TEA's reliability and validity and determined minimal clinically important differences (MIDs) in participants with moderate to severe OUD. Patients and methods: The TEA measures change in four single-item domains (substance use, health, lifestyle, community involvement) from treatment initiation across the duration of a treatment program. Self-reported responses range from 1 ("none or not much") to 10 ("much better") with items summed to a total score ranging from 4-40. We assessed floor and ceiling effects, internal consistency, test-retest reliability, known-groups validity (ANOVA stratified by current health status [36-Item Short Form Health Survey item 1]), convergent/divergent validity, and MIDs using data from a phase 3, open-label clinical trial of buprenorphine extended-release monthly injection for subcutaneous use (BUP-XR). Participants with OUD completed the TEA at screening and before monthly injections for up to 12 months. Results: Among 410 participants (mean age 38 years; 64% male), the mean baseline (pre-injection 1) TEA total score was 25.4 (SD 9.7), with <10% of participants at the measure floor and 10%-20% at the ceiling across domains. Internal consistency was high (Cronbach's α=0.90), with marginal test-retest reliability (intraclass correlation coefficient =0.69). Mean TEA total score consistently increased from baseline (n=410; mean 25.4 [SD 9.7]) to end of study (n=337; 35.0 [6.7]) and differentiated between current health status groups (P<0.001); it was weakly correlated with other measures of health-related quality of life/severity. MIDs ranged from 5-8 for the TEA total score across anchor- and distribution-based approaches. Conclusion: The TEA exhibited acceptable reliability and validity in a cohort of participants with moderate to severe OUD treated with BUP-XR. Given its brevity and psychometric properties, the TEA is a promising tool for use in clinical practice and research.

Patient-centered Outcomes in Participants of a Buprenorphine Monthly Depot (BUP-XR) Double-blind, Placebo-controlled, Multicenter, Phase 3 Study.

OBJECTIVE: Opioid use disorder (OUD) is associated with physical, social, psychological, and economic burden. This analysis assessed the effects of RBP-6000, referred to as BUP-XR (extended-release buprenorphine), a subcutaneously injected, monthly buprenorphine treatment for OUD compared with placebo on patient-centered outcomes measuring meaningful life changes. METHODS: Patient-centered outcomes were collected in a 24-week, phase 3, placebo-controlled study assessing the efficacy, safety, and tolerability of BUP-XR 300/300 mg (6 × 300 mg) and 300/100 mg (2 × 300 mg followed by 4 × 100 mg) injections in treatment-seeking participants with moderate-to-severe OUD. Measures included the EQ-5D-5L, SF-36v2, Medication Satisfaction Questionnaire, employment/insurance status, and healthcare resource utilization (HCRU). Changes from baseline to end of study were compared across treatment arms, using mixed models for repeated measures. RESULTS: Participants receiving BUP-XR (n = 389) versus placebo (n = 98) had significantly greater changes from baseline on the EQ-5D-5L index (300/300 mg: difference = 0.0636, P = 0.003), EQ-5D-5L visual analog scale (300/300 mg: difference = 5.9, P = 0.017; 300/100 mg: difference = 7.7, P = 0.002), and SF-36v2 physical component summary score (300/300 mg: difference = 3.8, P < 0.001; 300/100 mg: difference = 3.2, P = 0.002). Satisfaction was significantly higher for participants receiving BUP-XR 300/300 mg (88%, P < 0.001) and 300/100 mg (88%, P < 0.001) than placebo (46%). Employment and percentage of insured participants increased by 10.8% and 4.1% with BUP-XR 300/300 mg and 10.0% and 4.7% with 300/100 mg but decreased by 12.6% and 8.4% with placebo. Participants receiving BUP-XR compared with placebo had significantly fewer hospital days per person-year observed. CONCLUSIONS: These results show the feasibility of measuring patient-centered life changes in substance use disorder clinical studies. Participants receiving up to 6 monthly injections of BUP-XR, compared with placebo, reported better health, increased medication satisfaction, increased employment, and decreased healthcare utilization.

Efficacy and safety of a monthly buprenorphine depot injection for opioid use disorder: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: RBP-6000, referred to as BUP-XR (extended-release buprenorphine), is a subcutaneously injected, monthly buprenorphine treatment for opioid use disorder. BUP-XR provides sustained buprenorphine plasma concentrations to block drug-liking of abused opioids over the entire monthly dosing period, while controlling withdrawal and craving symptoms. Administration of BUP-XR in a health-care setting also mitigates abuse, misuse, diversion, and unintentional exposure. We aimed to investigate the efficacy of different BUP-XR dosing regimens in participants with opioid use disorder. METHODS: This randomised, double-blind, placebo-controlled, phase 3 trial was done at 36 treatment centres in the USA. Treatment-seeking adults aged 18-65 years who had moderate or severe opioid use disorder (as defined by the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders) entered an open-label run-in phase of up to 2 weeks' treatment with buprenorphine-naloxone sublingual film. Eligible participants were then randomly assigned (4:4:1:1) with an interactive voice/web-response system to receive BUP-XR 300 mg/300 mg (six injections of 300 mg), BUP-XR 300 mg/100 mg (two injections of 300 mg plus four injections of 100 mg), or volume-matched placebo every 28 days, and received weekly individual drug counselling. No supplemental buprenorphine was allowed. The primary efficacy endpoint was participants' percentage abstinence from opioid use, defined as the percentage of each participant's negative urine samples and self-reports of illicit opioid use from week 5 to week 24, analysed in the full analysis set. Safety was assessed in all participants who received at least one dose of BUP-XR or placebo. This study is registered with ClinicalTrials.gov, number NCT02357901. FINDINGS: From Jan 28, 2015, to Nov 12, 2015, 1187 potential participants were screened, 665 entered run-in, and 504 received BUP-XR 300 mg/300 mg (n=201), BUP-XR 300 mg/100 mg (n=203), or placebo (n=100). Mean participants' percentage abstinence was 41·3% (SD 39·7) for BUP-XR 300 mg/300 mg and 42·7% (38·5) for 300 mg/100 mg, compared with 5·0% (17·0) for placebo (p<0·0001 for both BUP-XR regimens). No compensatory non-opioid drug use was observed during BUP-XR treatment. The most common adverse events were headache (17 [8%] participants in the BUP-XR 300 mg/300 mg group vs 19 [9%] participants in the BUP-XR 300 mg/100 mg group vs six [6%] participants in the placebo group), constipation (16 [8%] vs 19 [9%] vs 0), nausea (16 [8%] vs 18 [9%] vs five [5%]), and injection-site pruritis (19 [9%] vs 13 [6%] vs four [4%]). The BUP-XR safety profile was consistent with other buprenorphine products for treatment of opioid use disorder, except for injection-site reactions, which were reported in more than 5% of all participants who received BUP-XR, but were mostly mild and not treatment-limiting. INTERPRETATION: Participants' percentage abstinence was significantly higher in both BUP-XR groups than in the placebo group. Treatment with BUP-XR was also well tolerated. The availability of this monthly formulation, delivered by health-care providers, represents an advance in treatment for opioid use disorder that enhances the benefits of buprenorphine by delivering sustained, optimal exposure, while reducing risks of current buprenorphine products. FUNDING: Indivior.

Remission from chronic opioid use-Studying environmental and socio-economic factors on recovery (RECOVER): Study design and participant characteristics.

Few opioid use disorder (OUD) treatment studies measure meaningful life changes during long-term recovery, focusing instead on retention and abstinence. Here, we report on the design and participant characteristics of the RECOVER study, a study exploring life changes in persons with OUD for up to 24 months following participation in a Phase III trial evaluating buprenorphine extended-release monthly injection for subcutaneous use (known as RBP-6000 during development). This multisite, observational, cohort study tracks clinical, environmental, and socio-economic changes using self-administered assessments, urine drug screens (UDS), and public databases. Outcomes include demographics (e.g., patient characteristics, employment history, criminal history), lifetime and recent OUD drug use and treatment, and current health and resource use. Demographic and psychosocial characteristics are compared to a national, population-based study. RECOVER participants (N = 533) tend to be single, white, males aged 26 years or older. Mean age at first opioid use was 21.7 years; lifetime substance-related overdose was 24.2%. At first assessment, 334 (62.7%) participants reported past 7-day and 296 (55.5%) reported past 28-day opioid abstinence. Five hundred UDS were collected at the first assessment; buprenorphine (90.6%), marijuana (45.2%), and opiates (34.4%) were most commonly identified. Two hundred forty-nine (47.2%) participants reported full- or part-time employment. Participants were like a national sample with differences found for age, race/ethnicity, employment, education, and health-related quality of life. We hope that further research using this approach can provide data supporting the patient-centered development of OUD treatments and be adopted by substance use disorder studies to incorporate recovery-related, life-activity outcomes.

Relationship between buprenorphine adherence and relapse, health care utilization and costs in privately and publicly insured patients with opioid use disorder.

BACKGROUND: Treatment for opioid use disorder is important because of the negative health, societal and economic consequences of illicit opioid use, but treatment adherence can be a challenge. This study assessed the association between buprenorphine medication-assisted treatment (MAT) adherence and relapse, health care utilization and costs. PATIENTS AND METHODS: Patients with opioid use disorder who were newly initiating a buprenorphine MAT regimen were identified in the 2008-2014 MarketScan® Commercial and Medicaid Databases and followed for 12 months after their earliest outpatient pharmacy claim for buprenorphine. Adherence was categorized using proportion of days covered (PDC) with buprenorphine, and patients with PDC≥0.80 were classified as adherent. Descriptive and adjusted analyses compared relapse prevalence, utilization and costs, all measured in the 12 months following buprenorphine MAT initiation, of adherent patients to patients in non-adherent PDC categories (PDC<0.20, 0.20≤PDC<0.40, 0.40≤PDC<0.60, 0.60≤PDC<0.80). RESULTS: Adherent patients were 37.1% of the Commercial sample (N=16,085) and 41.3% of the Medicaid sample (N=5,688). In both samples, non-adherent patients were significantly more likely than adherent patients to relapse and to have hospitalizations and emergency department visits. As a result, as buprenorphine MAT adherence increased, pharmacy costs increased, but medical costs decreased. Total costs (pharmacy plus medical costs) in the 12 months following buprenorphine MAT initiation decreased with adherence in Commercial patients ($28,525 for PDC<0.20 to $17,844 for PDC≥0.80). A slight decrease in total costs in the 12 months following buprenorphine MAT initiation was also observed in Medicaid patients ($21,292 for PDC<0.20 to $18,621 for PDC≥0.80). After adjustment, total costs of adherent patients in the Commercial sample ($17,519) were significantly lower compared with those of non-adherent patients (range $20,294-$24,431). In the Medicaid sample, adjusted total costs were not significantly different between adherence groups. CONCLUSION: Buprenorphine MAT adherence in the 12 months following treatment was associated with reduced odds of relapse and reduced unadjusted medical costs. For Commercial patients who were adherent to treatment, the adjusted total costs were predicted to be 30% lower than those for patients with PDC<0.20.

Characteristics and treatment patterns of US commercially insured and Medicaid patients with opioid dependence or abuse.

OBJECTIVE: To identify the demographic and clinical characteristics of commercially insured and Medicaid patients with a diagnosis of opioid dependence or abuse and to describe the pharmacological and nonpharmacological treatments received by these patients. DESIGN: This was a retrospective observational study using de-identified administrative claims data. SETTING: The analysis included commercially insured and Medicaid patient data extracted from the Truven Health MarketScan® Commercial and Medicaid Databases. PATIENTS: Patients with a diagnosis of opioid dependence or abuse from 2008 to 2014 (earliest diagnosis = index date) and a minimum of 6 months of pre-index and postindex continuous enrollment in the database. MAIN OUTCOME MEASURE(S): Baseline demographic and clinical characteristics, medication-assisted treatment (MAT), and treatment other than MAT received following diagnosis, and the clinical practice setting in which patients received any opioid dependence-related care were reported. RESULTS: Data from commercially insured (N = 103,768) and Medicaid (N = 50,552) patients were analyzed. Common comorbid conditions included chronic pain (48.6 percent Commercial, 56.8 percent Medicaid), depressive disorder (24.0 percent Commercial, 32.8 percent Medicaid), and other substance abuse disorders (13.3 percent Commercial, 23.7 percent Medicaid). Nearly one third of both Commercial (31.6 percent) and Medicaid (33.6 percent) patients did not have any claims for psychosocial therapy or MAT during the follow-up period. Only 24.3 percent of Commercial patients and 20.4 percent of Medicaid patients had evidence of claims for both MAT and psychosocial treatment anytime following diagnosis. CONCLUSIONS: The results suggest that there are opportunities to improve care through comprehensive and coordinated treatment for opioid dependence/abuse. Policies aimed at improving treatment access may be warranted.

Heterogeneity of nonadherent buprenorphine patients: subgroup characteristics and outcomes.

OBJECTIVES: To examine patient characteristics and outcomes associated with nonadherence to buprenorphine and to identify specific patterns of nonadherent behavior. STUDY DESIGN: Cross-sectional, retrospective analysis of health claims data. METHODS: Aetna's administrative claims data were used to categorize incident opioid use disorder (OUD) patients based on buprenorphine medication possession ratio (MPR) into adherent (n = 172) and nonadherent (n = 305) groups. Adherent groups were then divided into 5 subgroups based on level of MPR, as well as 2 a priori-defined groups: intermittent adherent (IA) and early treatment discontinuation-no consequences (ETDNC). Groups were compared on patient characteristics and outcomes. RESULTS: Nonadherent members incurred significantly greater healthcare costs and were more likely to relapse (P <.05). The use of high-cost healthcare services increased as a function of decreasing MPR (P <.05). Assessment of the a priori groups revealed IA members to have outcomes similar to nonadherent patients, while ETDNC members exhibited outcomes similar to adherent members. CONCLUSIONS: Administrative claims can be used to define subgroups of buprenorphine-medication assisted treatment (B-MAT) patients. Nonadherence was related to an increased likelihood of relapse, and there is an inverse relationship between MPR and cost. The heterogeneity observed within this sample indicates that treatment regimens effective for 1 subgroup may not be appropriate for all OUD patients. Increased understanding of B-MAT nonadherent subgroups may facilitate development of new interventions and medications specifically designed for nonadherent B-MAT patients, potentially leading to improved outcomes and reduced costs of care.

Factors associated with opioid overdose: a 10-year retrospective study of patients in a large integrated health care system.

OBJECTIVE: Opioid overdoses (ODs) have been increasing, and harm reduction efforts are a priority. The success of these efforts will be dependent on the identification of at-risk patients and improved access to the antidote naloxone. Therefore, to identify access to naloxone and factors associated with negative health outcomes, we conducted a retrospective study of patients with OD to identify those at highest risk of adverse outcomes and to assess the use of naloxone. METHODS: We conducted a study of electronic health records for patients admitted to the largest multihospital system in the region - the Geisinger Health System (GHS) for ODs - from April 2005 through March 2015. ODs were defined by International Classification of Diseases-9 codes (age range: 10-95 years). Bivariate analyses and multiple logistic regressions were conducted to identify pre-OD factors associated with adverse health outcomes post-OD. RESULTS: We identified 2,039 patients with one or more ODs, of whom 9.4% were deceased within 12 months. Patient demographics suggest that patients with OD had a mean age of 52 years, were not married (64%), and were unemployed (78%). Common comorbidities among patients with OD include cardiovascular disease (22%), diabetes (14%), cancer (13%), and the presence of one or more mental health disorders (35%). Few patients had a prescription order for naloxone (9%) after their OD. The majority of patients with OD were in proximity to GHS health care facilities, with 87% having a GHS primary care provider. In multiple logistic regressions, common predictors of adverse outcomes, including death, repeated ODs, frequent service use, and high service cost, were higher prescription opioid use, comorbid medical conditions, comorbid mental disorders, and concurrent use of other psychotropic medications. CONCLUSION: This study suggests opportunities for improving OD outcomes. Those who receive higher quantities of prescription opioids concurrent with other psychotropic medicines may need closer monitoring to avoid death, repeated OD events, higher service use, and higher service costs. Other opportunities for improving OD outcomes include the use of electronic health records to notify physicians of high-risk patients and updating of guidelines/operation manuals focused on the distribution of naloxone to those in highest need.

Health-related quality of life in acute schizophrenia patients treated with RBP-7000 once monthly risperidone: An 8-week, randomized, double-blind, placebo-controlled, multicenter phase 3 study.

BACKGROUND: There is increased interest in the impact of new long-acting treatments on health-related quality of life (HRQoL) in patients with schizophrenia. The aim of this study was to evaluate the impact of treatment with subcutaneous injections of RBP-7000, a new sustained-release formulation of risperidone, compared with placebo on health status, subjective well-being, treatment satisfaction, and preference of medicine in subjects with acute schizophrenia. METHODS: HRQoL data were derived from an 8-week double-blind, randomized, placebo-controlled, phase 3 study that assessed efficacy, safety, and tolerability of once monthly RBP-7000 (90mg and 120mg) compared with placebo in subjects with acute schizophrenia (n=337). HRQoL was measured with the EuroQol EQ-5D-5L, well-being using the Neuroleptic Treatment-Short Version (SWN-S), satisfaction using the Medication Satisfaction Questionnaire (MSQ), and preference using the Preference of Medicine Questionnaire (POM). RESULTS: The EQ-5D-5L VAS increased significantly in the RBP-7000 120mg group compared to Placebo (p=0.0212). In RBP-7000 120mg, subjects reported significant improvements in SWN-S physical functioning (p=0.0093), social integration (p=0.0368), and total score (p=0.0395). Subjects were significantly more satisfied with RBP-7000 versus placebo (90mg p=0.0009, 120mg p=0.0006) and preferred RBP-7000 over their previous medication (90mg p<0.0001, 120mg p=0.0619). CONCLUSIONS: Significantly greater improvements in HRQoL and overall well-being were demonstrated in patients randomized to RBP-7000 compared to placebo. The effect was more pronounced in the RBP-7000 120mg group. Patient satisfaction improved significantly and patient preference for their medicine favored RBP-7000 90mg and 120mg versus Placebo.

Cost effectiveness of enoxaparin as prophylaxis against venous thromboembolic complications in acutely ill medical inpatients: modelling study from the hospital perspective in Germany.

OBJECTIVE: To estimate, from the hospital perspective in Germany, the cost effectiveness of the low-molecular-weight heparin (LMWH) subcutaneous enoxaparin sodium 40 mg once daily (ENOX) relative to no pharmacological prophylaxis (NPP) and relative to subcutaneous unfractionated heparin (UFH) 5,000 IU three times daily (low-dose UFH [LDUFH]). Each is used in addition to elastic bandages/compression stockings and physiotherapy in the prevention of venous thromboembolic events (VTE) in immobilised acutely ill medical inpatients without impaired renal function or extremes of body weight. METHODS: The incremental cost-effectiveness ratios (ICERs) of the 'additional cost for ENOX per clinical VTE avoided versus NPP' and 'additional cost for ENOX per episode of major bleeding avoided versus LDUFH' were chosen as target variables. The target variables were quantified using a modelling approach based on the decision-tree technique. Resource use during thromboprophylaxis, diagnosis and treatment of VTEs, episode of major bleeding and secondary pneumonia after pulmonary embolism (PE) was collected from a hospital survey. Costs were exclusively those to hospitals incurred by staff expenses, drugs, devices, disposables, laboratory tests and equipment for diagnostic procedures. These costs were determined by multiplying utilised resource items by the price or tariff of each item as of the first quarter of 2003. Safety and efficacy values of the comparators were taken from the MEDENOX (prophylaxis in MEDical patients with ENOXaparin) and the THE-PRINCE (THromboEmbolism-PRevention IN Cardiac or respiratory disease with Enoxaparin) trials and from a meta-analysis. The evaluation encompassed 8 (6-14) days of thromboprophylaxis plus time to treat VTE and episode of major bleeding in hospital. Point estimates of all model parameters were applied exclusively in the base-case analysis. RESULTS: There were incremental costs of euro 1,106 for ENOX per clinical VTE avoided versus NPP (1 euro approximately equals 1.07 US dollars; average of the first quarter of 2003). ENOX dominated LDUFH: cost savings of euro 55,825 were obtained and 7.7 episodes of major bleeding were avoided by ENOX compared with LDUFH, each per 1000 patients. In comprehensive sensitivity analyses, the robustness of the model and its results was shown. CONCLUSIONS: Results of this evaluation suggest that, in immobilised acutely ill medical inpatients, ENOX may offer hospitals in Germany a very cost-effective option for thromboprophylaxis compared with NPP and a cost-saving alternative compared with LDUFH.

Economic burden of long-term complications of deep vein thrombosis after total hip replacement surgery in the United States.

BACKGROUND: Estimates of the cost of long-term complications of a primary deep vein thrombosis (DVT), including the post-thrombotic syndrome (PTS) and recurrent venous thromboembolism (VTE), may be relevant for resource allocation decisions. OBJECTIVE: The objective of this study was to provide US cost estimates of the long-term complications of a primary DVT, which occurs in approximately 5% to 20% (with adequate thromboprophylaxis) and 50% (in the absence of thromboprophylaxis) of total hip replacement surgeries (THRS). METHODS: A literature-based model was used to project the excess long-term complication costs of DVT following THRS. The model simulated the natural history of DVT complications using published estimates of the incidence and prognosis of PTS and recurrent VTE. Each complication was assigned a cost obtained by multiplying the amount of resources used in its management by the unit price of these resources. RESULTS: The annual per-patient cost of each complication was as follows: mild-to-moderate PTS, 839 dollars in the first year and 341 dollars in subsequent years; severe PTS, 3817 dollars in the first year and 1677 dollars in subsequent years; DVT, 3798 dollars; and pulmonary embolism, 6604 dollars. The average discounted lifetime cost of DVT complications was estimated to be 3069 dollars (95% interval 2091 dollars-4279 dollars). CONCLUSIONS: The long-term complications of a primary DVT represent a significant economic burden. Preventing a DVT could arguably lead to substantial savings in long-term DVT complications.