Patterns of initial ovarian cancer recurrence on niraparib maintenance monotherapy in patients with no baseline evidence of disease after first-line chemotherapy: An ad hoc subgroup analysis of PRIMA/ENGOT-OV26/GOG-3012.

OBJECTIVES: Patterns of disease recurrence on poly(ADP-ribose) polymerase inhibitor maintenance therapy are unclear and may affect subsequent treatment. This ad hoc subgroup analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 study evaluated patterns of initial recurrence in patients with advanced ovarian cancer (AOC). METHODS: PRIMA included participants at high risk for disease progression. This ad hoc analysis only evaluated participants randomized to niraparib maintenance without evidence of disease at baseline. The number and site(s) of initial recurrent lesions at investigator-assessed progressive disease (PD) were evaluated. RESULTS: Of the 314 niraparib-treated patients analyzed, 190 developed ≥1 new lesion (median number of new lesions, 1.0; interquartile range, 1-2). In total, 93.2% (177/190) of patients developed 1-3 lesions at first disease progression. The most common sites of recurrence were the peritoneum (30.0% [57/190]), lymph nodes (26.3% [50/190]), and liver (20.5% [39/190]). Similar results were observed when patients with PD were stratified by biomarker status, disease stage at diagnosis, and type of debulking surgery. Patients with homologous recombination-proficient tumors, stage III disease, or a history of primary debulking developed a median of 2.0 new lesions at first progression; patients with homologous recombination-deficient tumors, stage IV disease, or a history of interval debulking developed a median of 1.0 new lesion. CONCLUSIONS: Many patients with AOC without lesions at first-line maintenance treatment initiation develop oligometastatic disease at first recurrence. Prospective evaluation is required to determine whether these patients have improved outcomes when local therapies are combined with continuous, systemic, targeted maintenance therapy.

Efficacy and safety of niraparib in patients aged 65 years and older with advanced ovarian cancer: Results from the PRIMA/ENGOT-OV26/GOG-3012 trial.

OBJECTIVE: To evaluate the impact of age on the efficacy and safety of niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer with a complete/partial response to first-line platinum-based chemotherapy. METHODS: Post hoc analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 study (NCT02655016). Patients in the intent-to-treat population were categorized according to age at baseline (<65 years vs ≥65 years), and progression-free survival (PFS), safety, and health-related quality of life (HRQOL) were evaluated for each age subgroup (clinical cutoff date, May 17, 2019). Safety findings were also evaluated according to a fixed starting dose (FSD) or an individualized starting dose (ISD). RESULTS: Of 733 randomized patients, 289 (39.4%) were ≥65 years (190 niraparib, 99 placebo) at baseline. Median PFS (niraparib vs placebo) and hazard ratios (95% CI) were similar in patients aged <65 years (13.9 vs 8.2 months; HR, 0.61 [0.47-0.81]) and ≥65 years (13.7 vs 8.1 months; HR, 0.53 [0.39-0.74]). The incidences of any-grade and grade ≥3 treatment-emergent adverse events (TEAEs) were similar across age subgroups; in the niraparib arm, TEAEs leading to dose discontinuation occurred in 7.8% of patients <65 years and 18.4% of patients ≥65 years. ISD use lowered the incidence of grade ≥3 thrombocytopenia events in niraparib-treated patients compared with the FSD (<65 years: 42.8% vs 18.0%; ≥65 years 57.0% vs 26.1%). HRQOL was comparable across age subgroups. CONCLUSION: Niraparib efficacy, safety, and HRQOL were generally comparable across age subgroups, although patients ≥65 years had a higher rate of discontinuations due to TEAEs. ISD use reduced grade ≥3 thrombocytopenia events regardless of age.

Ovarian Cancer Retrospective European (O'CaRE) study: first-line outcomes by number of risk factors for progression.

Aim: The Ovarian Cancer Retrospective European (O'CaRE) study assessed the cumulative impact of high-risk factors on progression-free survival (PFS) and overall survival (OS) following first-line treatment in patients diagnosed with advanced ovarian cancer.Patients & methods: Medical records were collected from five European countries (2014 and 2015). Patients were grouped by number of high-risk factors: stage IV diagnosis, no known BRCA mutation, interval debulking surgery or no surgery, or visible residual disease.Results: Our analysis included 405 patients grouped based on having one (20.4%); two (32.3%); three (33.7%) or four (11.9%) high-risk factors. Increasing cumulative numbers of high-risk factors were associated with numerically shorter PFS and OS.Conclusion: Risk profiles should be carefully considered when planning clinical care.

Does the number of risk factors a person with advanced ovarian cancer have affect the likely success of their cancer treatment?What is already known on this topic? Studies have found that individual factors, such as disease stage, and whether any cancer cells remain after surgery are linked to earlier disease worsening and/or shorter survival after treatment in people with advanced ovarian cancer. These are known as 'risk factors'. However, few studies have looked at whether this link is stronger if a person has several of these risk factors.What does this study add? In this study, we looked at whether outcomes after treatment worsen as the number of risk factors increases. We found that patients with more high-risk factors saw a worsening of their cancer much sooner than those with a fewer number of risk factors. Also, patients with multiple risk factors did not live as long as patients with fewer risk factors.How might this study affect research, practice or policy? When selecting therapies, healthcare providers should consider the impact of patient risk factors on how effectively that treatment will treat their cancer. The number of high-risk factors may also make an important difference in clinical trials and, therefore, should be considered when comparing results from different clinical trials.

Predictors of long-term progression-free survival in patients with ovarian cancer treated with niraparib in the PRIMA/ENGOT-OV26/GOG-3012 study.

OBJECTIVE: To identify characteristics associated with long-term progression-free survival (≥2 years) in patients with advanced ovarian cancer treated with niraparib first-line maintenance therapy in the phase III PRIMA/ENGOT-OV26/GOG-3012 study. METHODS: In this post hoc analysis of PRIMA, patients randomized to niraparib were grouped based on investigator-assessed progression-free survival (progressive disease/censoring <2 years or ≥2 years after randomization). Variables assessed for predictive value were Eastern Cooperative Oncology Group performance status, International Federation of Gynecology and Obstetrics (FIGO) stage at diagnosis, clinical response to platinum-based chemotherapy, number of prior chemotherapy cycles, primary tumor location, body mass index, categorical age, debulking surgery type, number of baseline target lesions, number of baseline non-target lesions, BRCA/homologous recombination-deficiency status, residual disease status, and duration from end of chemotherapy to randomization. Logistic regression modeling using backward elimination (significance level=0.15) identified covariates associated with long-term progression-free survival (clinical cut-off date November 17, 2021). RESULTS: Of 487 patients randomized to niraparib, 152 (31%) had progressive disease/censoring ≥2 years after randomization. Multivariable logistic regression modeling using backward elimination identified BRCA1/2 mutation/homologous recombination deficiency status (p<0.0001), FIGO stage (p=0.041), primary tumor location (p=0.095), and number of baseline non-target lesions (p=0.0001) to be associated with long-term progression-free survival. Patients significantly more likely to achieve progression-free survival of ≥2 years in the final model were those with BRCA1- and BRCA2-mutated/homologous recombination-deficient tumors or BRCA wild-type/not determined/homologous recombination-deficient tumors (vs BRCA wild-type/homologous recombination-proficient/not determined tumors), FIGO stage III (vs IV), and 0 or 1 baseline non-target lesions (vs ≥2 baseline non-target lesions). CONCLUSIONS: The hypothesis-generating results of this analysis suggest that BRCA1/2 mutation/homologous recombination-deficiency status, FIGO stage, and number of baseline non-target lesions may predict progression-free survival of ≥2 years in patients with advanced ovarian cancer receiving niraparib first-line maintenance therapy. TRIAL REGISTRATION NUMBER: NCT02655016.

Optimizing disease progression assessment using blinded central independent review and comparing it with investigator assessment in the PRIMA/ENGOT-ov26/GOG-3012 trial: challenges and solutions.

OBJECTIVE: Progression-free survival is an established clinically meaningful endpoint in ovarian cancer trials, but it may be susceptible to bias; therefore, blinded independent centralized radiological review is often included in trial designs. We compared blinded independent centralized review and investigator-assessed progressive disease performance in the PRIMA/ENGOT-ov26/GOG-3012 trial examining niraparib monotherapy. METHODS: PRIMA/ENGOT-ov26/GOG-3012 was a randomized, double-blind phase 3 trial; patients with newly diagnosed stage III/IV ovarian cancer received niraparib or placebo. The primary endpoint was progression-free survival (per Response Evaluation Criteria in Solid Tumors [RECIST] v1.1), determined by two independent radiologists, an arbiter if required, and by blinded central clinician review. Discordance rates between blinded independent centralized review and investigator assessment of progressive disease and non-progressive disease were routinely assessed. To optimize disease assessment, a training intervention was developed for blinded independent centralized radiological reviewers, and RECIST refresher training was provided for investigators. Discordance rates were determined post-intervention. RESULTS: There was a 39% discordance rate between blinded independent centralized review and investigator-assessed progressive disease/non-progressive disease in an initial patient subset (n=80); peritoneal carcinomatosis was the most common source of discordance. All reviewers underwent training, and as a result, changes were implemented, including removal of two original reviewers and identification of 10 best practices for reading imaging data. Post-hoc analysis indicated final discordance rates between blinded independent centralized review and investigator improved to 12% in the overall population. Median progression-free survival and hazard ratios were similar between blinded independent centralized review and investigators in the overall population and across subgroups. CONCLUSION: PRIMA/ENGOT-ov26/GOG-3012 highlights the need to optimize blinded independent centralized review and investigator concordance using early, specialized, ovarian-cancer-specific radiology training to maximize validity of outcome data.

Niraparib treatment for patients with BRCA-mutated ovarian cancer: review of clinical data and therapeutic context.

We reviewed clinical data for niraparib monotherapy in BRCA-mutated (BRCAm) epithelial ovarian cancer (OC), contextualizing results with data from other poly(ADP-ribose) polymerase inhibitors (PARPis). Niraparib reduced the likelihood of progression or death by 60% as first-line maintenance therapy and by 73-78% in recurrent disease. In heavily pretreated OC, efficacy was greater in the BRCAm versus non-BRCAm cohort. Quality-of-life (QoL) was maintained throughout treatment. Adverse events were consistent with the known niraparib safety profile. Cumulative efficacy, safety and QoL evidence demonstrate niraparib maintenance monotherapy has a positive benefit:risk ratio in BRCAm OC. Niraparib significantly improved progression-free survival as first-line maintenance therapy in all patients with OC (i.e., of any biomarker status).

This article reviewed niraparib monotherapy in patients with ovarian cancer (OC) who have mutations in a specific gene (BRCA). Across multiple clinical trials, niraparib maintenance treatment was able to delay further progression of disease or death compared with patients who had received placebo; the tumors of patients who had received extensive prior treatment for OC were also more likely to respond to niraparib treatment. Patients were able to have the same quality-of-life with niraparib as they would if they had not received treatment. Side effects were predictable from previous clinical trial experience. Together, these data show that niraparib, like other inhibitors of poly(ADP-ribose) polymerase, is beneficial in patients with OC who have a deleterious BRCA mutation. A plain language version of this article is available and is published alongside the paper online: www.futuremedicine.com/doi/suppl/10.2217/fon-2022-0206.

Efficacy of a community-based participatory and multilevel intervention to enhance hepatitis B virus screening and vaccination in underserved Korean Americans.

BACKGROUND: The primary objective of the current study was to evaluate the efficacy of a community-based participatory intervention program in improving hepatitis B virus (HBV) screening and vaccination among Korean Americans who were not previously screened. METHODS: A cluster randomized trial involving 32 Korean church-based community organizations (1834 participants) was conducted. Sixteen churches were randomly assigned to an HBV screening and vaccination multicomponent intervention condition (972 participants) and 16 were assigned to a general cancer education control condition (862 participants). The main components of the intervention program included interactive group education; patient navigation; and the engagement of health care providers, church leadership, and church members in the medical field. The application of community-based participatory research principles was monitored and evaluated. HBV screening and vaccination rates (self-reported and medical record verification) were assessed at 6-month and 12-month follow-ups, respectively. RESULTS: The results of the current study demonstrated significant efficacy in the HBV screening rate (92.5% in the intervention group vs 5.5% in the control group), 3-series HBV vaccination completion rate (84% in the intervention group vs 17.6% in the control group), and overall screening and vaccination compliance rate (87% in the intervention group vs 3.8% in the control group). Participants in the intervention group were significantly more likely to receive HBV screening (92.5%) compared with those in the control group (5.5%). In multivariate mixed-effect logistic regression analysis, the odds ratio for an intervention effect on HBV screening was 512.3 after adjusting for cluster effect and other demographic variables. With regard to vaccination rates, of the 332 participants who were screened with no immunity in the intervention group, 308 (92.8%) received at least 1 HBV vaccination, 300 (90.4%) received at least 2 shots, and 279 participants (84%) received all 3 shots. CONCLUSIONS: A combination of community-based participatory research and a multilevel approach may produce the most optimal results and be essential in producing a considerable effect for enhancing HBV screening and vaccination, particularly for Korean American populations with limited language proficiency and insurance coverage. Cancer 2018;124:973-82. © 2017 American Cancer Society.

Poor Concordance Between Cancer Antigen-125 and RECIST Assessment for Progression in Patients With Platinum-Sensitive Relapsed Ovarian Cancer on Maintenance Therapy With a Poly(ADP-ribose) Polymerase Inhibitor.

PURPOSE: Cancer antigen-125 (CA-125) is recommended by treatment guidelines and widely used to diagnose ovarian cancer recurrence. The value of CA-125 as a surrogate for disease progression (PD) and its concordance with radiologic progression are unclear, particularly for women with platinum-sensitive relapsed ovarian cancer (PSROC) who have responded to chemotherapy and treated with maintenance poly(ADP-ribose) polymerase inhibitor (PARPi). METHODS: In this pooled analysis of four randomized trials of maintenance PARPi or placebo (Study 19, SOLO2, ARIEL3, and NOVA), we extracted data on CA-125 PD as defined by Gynecologic Cancer InterGroup criteria and RECIST v1.1. We evaluated the concordance between CA-125 and RECIST PD and reported on the negative predictive value (NPV) and positive predictive value (PPV). RESULTS: Of 1,262 participants (n = 818 PARPi, n = 444 placebo), 403 (32%) had CA-125 PD, and of these, 366 had concordant RECIST PD (PPV, 91% [95% CI, 88 to 93]). However, of 859 (68%) without CA-125 PD, 382 also did not have RECIST PD (NPV, 44% [95% CI, 41 to 48]). Within the treatment arms, PPV remained high (PARPi, 91% [95% CI, 86 to 94]; placebo, 91% [95% CI, 86 to 95]) but NPV was lower on placebo (PARPi, 53% [95% CI, 49 to 57]; placebo, 25% [95% CI, 20 to 31]). Of 477 with RECIST-only PD, most (95%) had a normal CA-125 at the start of maintenance therapy and the majority (n = 304, 64%) had CA-125 that remained within normal range. Solid organ recurrence without peritoneal disease was more common in those with RECIST-only PD than in those with CA-125 and RECIST PD (36% v 24%; P < .001). CONCLUSION: In patients with PSROC treated with maintenance PARPi, almost half with RECIST PD did not have CA-125 PD, challenging current guidelines. Periodic computed tomography imaging should be considered as part of surveillance, particularly in those with a normal CA-125 at the start of maintenance therapy and on treatment.

Tolerability of the niraparib individualized starting dose in the PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib first-line maintenance therapy.

PURPOSE: To explore safety and tolerability parameters for the niraparib individualized starting dose (ISD) in patients with newly diagnosed advanced ovarian cancer that responded to platinum-based chemotherapy who participated in the phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial (NCT02655016). METHODS: The PRIMA protocol was amended so newly enrolled patients received an ISD based on baseline body weight/platelet count. In this ad hoc analysis, the timing, duration, and resolution of the first occurrence of common any-grade hematologic (thrombocytopenia, anemia, neutropenia) and nonhematologic (nausea, asthenia/fatigue, constipation, insomnia, hypertension) treatment-emergent adverse events (TEAEs) were evaluated by treatment arm in the ISD safety population (data cutoff, November 17, 2021; median follow-up, 3.5 years). RESULTS: Of 733 randomized patients, 255 were enrolled after the ISD protocol amendment and received ≥ 1 dose of study treatment (niraparib, 169; placebo, 86). In the niraparib arm, median times to first events were 22.0-35.0 days for hematologic TEAEs and 7.0-56.0 days for nonhematologic TEAEs. First events resolved in ≥ 89.8% of patients for hematologic TEAEs; for nonhematologic TEAEs, resolution rates ranged from 55.3% (insomnia) to 86.0% (nausea). Median durations of first hematologic TEAEs were ≤ 16.0 days, but for first nonhematologic TEAEs ranged from 18.0 days (nausea) to 134.0 days (insomnia). CONCLUSION: The niraparib ISD was generally well tolerated and TEAEs were manageable. Common hematologic and nonhematologic TEAEs occurred early and first events of hematologic TEAEs had a short duration (≈ 2 weeks) and a high resolution rate. These findings support close monitoring immediately following niraparib initiation and may help inform patient expectations for niraparib safety.

Use of Citrated Whole Blood for Point-of-Care Viscoelastic Coagulation Testing in Dogs.

Background: A new, portable bedside coagulation monitor (VCM Vet) has provided a user-friendly, cartridge-based method to perform viscoelastic testing. However, the use of native whole blood limits the time to analyze the sample to minutes. The objective of this study is to assess whether citrated whole blood can be utilized with the cartridge-based system and whether the results are comparable to those of native whole blood. A secondary objective is to assess the viability of citrated whole blood results after up to 4 hours of resting. Methods: The study population consisted of 10 healthy mixed breed dogs. Whole blood samples were collected via jugular venipuncture. Blood was immediately transferred to the VCM test cartridge for native whole blood control group analysis per the manufacturer's instructions, and the remainder was used to fill two 3.2% sodium citrate vacutainer tubes. Test group analysis was performed on samples from each tube concurrently after a rest period of 30 min (baseline), 2 h, and 4 h. Citrated whole blood samples were recalcified for analysis immediately prior to introduction into the test cartridge. Data was recorded for all reported parameters. Results from the citrate groups were compared to the control group and to the citrated baseline to assess for differences. Overall results were compared using mixed ANOVA models. Where found, specific differences were evaluated using Tukey's test. Within-sample variation was investigated and reported as median (range). A p < 0.05 was considered significant. Results: Samples were obtained for a total of 10 control runs and 20 citrated whole blood runs. Comparison of controls to the citrated test groups revealed significant differences in CT (p < 0.001) and MCF (p < 0.002). There were no significant differences between test groups compared to citrated baselines for any parameter. Selected median coefficients of variation were 6.8% (0-68.8%) for CT, 2.4% (0-19.46%) for alpha angle, 3.2% (0-27.4%) for MCF, and 0% (0-16.3%) for 45-min LY45. Conclusion: Citrated whole blood samples can be used with the VCM Vet device; however, new reference intervals for use with citrated whole blood will be required. Results using citrated whole blood samples are not significantly different from baseline after up to 4 h of resting.

A Phase I, Open-Label, Dose-Finding Study of GSK2636771, a PI3Kß Inhibitor, Administered with Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: In patients with metastatic castration-resistant prostate cancer (mCRPC), resistance to androgen receptor (AR)-targeted therapies, such as enzalutamide, remains an issue. Inactivation of inhibitory PTEN activates PI3K/AKT signaling and contributes to resistance to androgen deprivation therapy and poor outcomes. Therefore, dual targeting of AR and PI3K/AKT pathways may limit tumor growth and reverse resistance. PATIENTS AND METHODS: In this phase I study (NCT02215096), patients with PTEN-deficient mCRPC who progressed on prior enzalutamide received once-daily enzalutamide 160 mg plus PI3Kß inhibitor GSK2636771 at 300 mg initial dose, with escalation or de-escalation in 100-mg increments, followed by dose expansion. Primary objectives were to evaluate safety/tolerability, determine the recommended phase II dose, and assess the 12-week non-progressive disease (PD) rate. RESULTS: Overall, 37 patients were enrolled; 36 received ≥1 dose of GSK2636771 (200 mg: n = 22; 300 mg: n = 12; 400 mg: n = 2) plus 160 mg enzalutamide. Dose-limiting toxicities occurred in 5 patients (200 mg: n = 1; 300 mg: n = 2, 400 mg: n = 2). No new or unexpected adverse events or evidence of drug-drug interaction were observed. At the recommended dose of GSK2636771 (200 mg) plus enzalutamide, the 12-week non-PD rate was 50% (95% confidence interval: 28.2-71.8, n = 22); 1 (3%) patient achieved a radiographic partial response lasting 36 weeks. Four of 34 (12%) patients had prostate-specific antigen reduction of ≥50%. CONCLUSIONS: Although there was acceptable safety and tolerability with GSK2636771 plus enzalutamide in patients with PTEN-deficient mCRPC after failing enzalutamide, limited antitumor activity was observed.

Detecting schizophrenia early: Prediagnosis healthcare utilization characteristics of patients with schizophrenia may aid early detection.

INTRODUCTION: Many patients exhibit subsyndromal clinical findings of schizophrenia prior to diagnosis. Early treatment may mitigate schizophrenia development, yet little is known about comorbidities and healthcare resource utilization (HCRU) in these patients before diagnosis. METHODS: This retrospective, longitudinal cohort study, conducted between January 1, 2007 and April 30, 2016, used claims data from the US HealthCore Integrated Research Database. Newly diagnosed patients with schizophrenia (International Classification of Diseases, Ninth Revision: 295.x or ICD 10 F20.%) were identified and matched (1:4) with non-schizophrenia comparators. Patients were 15-54 years of age with either ≥1 inpatient/emergency room claim with a primary schizophrenia diagnosis, or ≥2 claims in any setting with any schizophrenia diagnosis. Demographics, comorbidities, physician specialties, medications, and related services, and other HCRU were compared between cohorts for up to 5 years before diagnosis. RESULTS: The schizophrenia cohort included 6732 patients (57.4% male, mean age 30.3 years for males and 36.2 years for females). All outcomes were more prevalent in the schizophrenia cohort than the comparator cohort. Substantial comorbidity, medication use, and HCRU were observed in the schizophrenia cohort even 4-5 years before diagnosis with increasing findings approaching diagnosis. From 4-5 years to 0-12 months before diagnosis, resource use increased from 20.5% to 53.3% for atypical antipsychotics, 29.3% to 48.2% for antidepressants, and 15.1% to 35.5% for psychiatric diagnostic examinations. CONCLUSIONS: Patients with schizophrenia extensively use healthcare resources up to 5 years before diagnosis. Our findings may help with developing predictive models to identify patients at high risk of schizophrenia.

Rate of preventative vaccine use and vaccine beliefs among a commercially insured population.

Immunization is an important component of preventive healthcare services. By recognizing and understanding factors associated with suboptimal vaccination compliance, healthcare providers can better approach at-risk populations and target efforts at reinforcing the vital importance of immunizations. The objective of this study was to understand the factors associated with adherence, beliefs and behaviors of influenza, pneumococcal, and herpes zoster vaccines receipt among commercially insured adults. A cross-sectional survey of patients with medical and pharmacy benefits for a 24-month period between August 1, 2014 and July 31, 2016 who were eligible to receive at least one of three adult vaccines (influenza, pneumococcal, and herpes zoster) was completed. Patients were identified as eligible to receive a vaccine based on current guidelines from the CDC ACIP. Health plan members were identified from administrative claims data in the HealthCore Integrated Research DatabaseSM (HIRD). Among the participants, 11% were eligible and up-to-date on all three vaccines; 52% on some and 37% were not up-to-date on any of the three vaccines. Participants with a healthcare provider were more likely to be up-to-date on eligible vaccines: 79.9% for none, 91.3% for some, and 97.8% for all eligible vaccines. The composite Vaccine Myth Belief score was significantly associated with being up to date on eligible vaccines: 45.0%/12.8% for none, 12/5%/30.8% for some, and 8.9%/33.3% for those up-to-date on all eligible vaccines. Despite numerous interventions designed to increase vaccination rates among adults, compliance remains suboptimal. It is evident that patient and provider education is necessary to fill knowledge gaps and misunderstandings; however knowledge by itself is not sufficient to improve immunization practices. Our results highlight a population that could benefit from a multidisciplinary approach, including interventions at the individual and health system levels.

Health Care Resource Utilization and Cost Before Initial Schizophrenia Diagnosis.

BACKGROUND: The management of schizophrenia, a chronic, multifaceted mental health condition, is associated with considerable health care resource utilization (HCRU) and costs. Current evidence indicates that a high-risk and costly prodromal period, during which patients are likely symptomatic, precedes diagnosis. Better characterization and disease management during this stage could help to improve patient outcomes. OBJECTIVE: To describe and compare HCRU and costs for up to 5 years before diagnosis in a cohort with schizophrenia versus a demographically matched cohort without schizophrenia in a commercially insured U.S. METHODS: This retrospective study identified newly diagnosed schizophrenia patients using enrollee claims in the HealthCore Integrated Research Database between January 1, 2007, and April 30, 2016. The index date was defined as the date of the first medical claim with a schizophrenia diagnosis code. Schizophrenia patients were directly matched (1:4) by age, sex, and region to comparators without schizophrenia who were assigned the same index dates as their matched schizophrenia counterparts. Observation periods were 0-12, 13-24, 25-36, 37-48, and 49-60 months before the index date. Outcomes included HCRU and costs for inpatient admissions, emergency room visits, outpatient care (office visits and other outpatient services), and medications. Means, standard deviations, medians, and 95% confidence intervals were calculated for continuous variables; relative frequencies and percentages were calculated for categorical variables. Cohorts were compared with t-tests for continuous variables and chi-square tests for categorical variables. Differences across cohorts were estimated with individual generalized linear models for each observation period, controlling for gender, age, geographic region of residence, health plan type and subscriber status, behavioral pre-index comorbidities and chronic comorbidities during the period before diagnosis. RESULTS: 6,732 schizophrenia patients were matched to 26,928 patients without schizophrenia. All-cause inpatient admissions were more prevalent among schizophrenia patients than their comparators for all time periods (49-60 months prediagnosis: 9% vs. 4%; 0-12 months prediagnosis: 33% vs. 4%). The schizophrenia cohort had higher adjusted all-cause per-patient per-month health care costs relative to comparators from the earliest period of 49-60 months prediagnosis ($557 [95% CI = 474-639] vs. $321 [95% CI = 288-355]) through 0-12 months prediagnosis ($1,058 [95% CI = 998-1,115] vs. $338 [95% CI = 320-355]). Behavioral health-related costs were different in each time period as were cost ratios (schizophrenia costs: comparator costs), which increased from 5.4 in the earliest period to 14.8 in the year before diagnosis. CONCLUSIONS: Schizophrenia patients had higher all-cause and behavioral health-related HCRU and costs before diagnosis than matched controls. Costs increased from 5 years to 1 year prediagnosis for schizophrenia patients driven primarily by inpatient hospital stays and prescription drug costs, but remained stable for comparators. Additional research is needed for the development of predictive models to aid in the identification of high-risk patients. DISCLOSURES: This study was sponsored by Boehringer Ingelheim Pharmaceuticals. Barron is an employee of HealthCore, which received funding from Boehringer Ingelheim to conduct this study. Wallace and York were employed by HealthCore at time of this study. Isenberg is an employee of Anthem. Franchino-Elder, Sidovar, and Sand are employees of Boehringer Ingelheim.

Health Care Resource Utilization and Cost Before Initial Schizophrenia Diagnosis.

BACKGROUND: The management of schizophrenia, a chronic, multifaceted mental health condition, is associated with considerable health care resource utilization (HCRU) and costs. Current evidence indicates that a high-risk and costly prodromal period, during which patients are likely symptomatic, precedes diagnosis. Better characterization and disease management during this stage could help to improve patient outcomes. OBJECTIVE: To describe and compare HCRU and costs for up to 5 years before diagnosis in a cohort with schizophrenia versus a demographically matched cohort without schizophrenia in a commercially insured U.S. METHODS: This retrospective study identified newly diagnosed schizophrenia patients using enrollee claims in the HealthCore Integrated Research Database between January 1, 2007, and April 30, 2016. The index date was defined as the date of the first medical claim with a schizophrenia diagnosis code. Schizophrenia patients were directly matched (1:4) by age, sex, and region to comparators without schizophrenia who were assigned the same index dates as their matched schizophrenia counterparts. Observation periods were 0-12, 13-24, 25-36, 37-48, and 49-60 months before the index date. Outcomes included HCRU and costs for inpatient admissions, emergency room visits, outpatient care (office visits and other outpatient services), and medications. Means, standard deviations, medians, and 95% confidence intervals were calculated for continuous variables; relative frequencies and percentages were calculated for categorical variables. Cohorts were compared with t-tests for continuous variables and chi-square tests for categorical variables. Differences across cohorts were estimated with individual generalized linear models for each observation period, controlling for gender, age, geographic region of residence, health plan type and subscriber status, behavioral pre-index comorbidities and chronic comorbidities during the period before diagnosis. RESULTS: 6,732 schizophrenia patients were matched to 26,928 patients without schizophrenia. All-cause inpatient admissions were more prevalent among schizophrenia patients than their comparators for all time periods (49-60 months prediagnosis: 9% vs. 4%; 0-12 months prediagnosis: 33% vs. 4%). The schizophrenia cohort had higher adjusted all-cause per-patient per-month health care costs relative to comparators from the earliest period of 49-60 months prediagnosis ($557 [95% CI = 474-639] vs. $321 [95% CI = 288-355]) through 0-12 months prediagnosis ($1,058 [95% CI = 998-1,115] vs. $338 [95% CI = 320-355]). Behavioral health-related costs were different in each time period as were cost ratios (schizophrenia costs: comparator costs), which increased from 5.4 in the earliest period to 14.8 in the year before diagnosis. CONCLUSIONS: Schizophrenia patients had higher all-cause and behavioral health-related HCRU and costs before diagnosis than matched controls. Costs increased from 5 years to 1 year prediagnosis for schizophrenia patients driven primarily by inpatient hospital stays and prescription drug costs, but remained stable for comparators. Additional research is needed for the development of predictive models to aid in the identification of high-risk patients. DISCLOSURES: This study was sponsored by Boehringer Ingelheim Pharmaceuticals. Barron is an employee of HealthCore, which received funding from Boehringer Ingelheim to conduct this study. Wallace and York were employed by HealthCore at time of this study. Isenberg is an employee of Anthem. Franchino-Elder, Sidovar, and Sand are employees of Boehringer Ingelheim.

Early life influences on child weight outcomes in the Study to Explore Early Development.

We examined associations between child body mass index at 2-5 years and maternal pre-pregnancy body mass index, gestational weight gain, and rapid weight gain during infancy in children with autism spectrum disorder, developmental delays, or population controls. The Study to Explore Early Development is a multi-site case-control study of children, aged 2-5 years, classified as autism spectrum disorder ( n = 668), developmental delays ( n = 914), or population controls ( n = 884). Maternal gestational weight gain was compared to the Institute of Medicine recommendations. Rapid weight gain was a change in weight-for-age z-scores from birth to 6 months > 0.67 standard deviations. After adjusting for case status, mothers with pre-pregnancy overweight/obesity were 2.38 times (95% confidence interval: 1.96-2.90) more likely, and mothers who exceeded gestational weight gain recommendations were 1.48 times (95% confidence interval: 1.17-1.87) more likely, to have an overweight/obese child than other mothers ( P < 0.001). Children with autism spectrum disorder showed the highest frequency of rapid weight gain (44%) and were 3.47 times (95% confidence interval: 1.85-6.51) more likely to be overweight/obese as children with autism spectrum disorder without rapid weight gain ( P < 0.001). Helping mothers achieve a healthy pre-pregnancy body mass index and gestational weight gain represent important targets for all children. Healthy infant growth patterns carry special importance for children at increased risk for an autism spectrum disorder diagnosis.

Real-world effectiveness, adherence and persistence among patients with type 2 diabetes mellitus initiating dulaglutide treatment.

OBJECTIVES: To assess glycemic effectiveness, adherence and persistence within 6 months of treatment initiation with dulaglutide, a once weekly GLP-1 receptor agonist, in a US real-world setting. METHODS: This retrospective claims analysis included adults (≥18 years) with T2DM from the HealthCore Integrated Research Database, who had HbA1c laboratory results around initiation and within 6 months after initiation. Glycemic control was assessed by change in HbA1c from pre-initiation to post-initiation. Patients were considered adherent if their proportion of days covered (PDC) was ≥0.80; persistence was measured as days of continuous therapy from initiation to 6 months after initiation with no gaps >45 days between fills. RESULTS: Of the 308 analyzed patients, the majority (n = 188; 61%) were adherent to dulaglutide (mean PDC 0.76; SD 0.26), with 115 patients (37%) discontinuing treatment. Mean persistence was 152 days/5 months. Mean HbA1c decreased from 8.49% (SD 1.70, median 8.20%) at baseline to 7.59% (SD 1.51, median 7.30%) at follow-up, corresponding to a mean HbA1c change of -0.90% (95% confidence interval [CI] -1.08 to -0.73; p < .01; median -0.70%). Patients who were adherent to or persistent with dulaglutide experienced larger reductions (-1.14% and -1.12% respectively), as did those without prior GLP-1 RA use (-1.03%). The proportion of patients with HbA1c <7% increased from 18% to 40%. CONCLUSIONS: Dulaglutide was associated with a significant decrease in HbA1c levels 6 months after treatment initiation. Patients who adhered to or persisted with dulaglutide therapy, or were naïve to GLP-1 RA use, experienced greater decreases in HbA1c levels.