Comparing Relapse Rates in Real-World Patients with Schizophrenia Who Were Adequately versus Not Adequately Treated with Paliperidone Palmitate Once-Monthly Injections Before Transitioning to Once-Every-3-Months Injections.

Purpose: This retrospective cohort study evaluated real-world data on relapses in adult patients with schizophrenia who transitioned to long-acting injectable paliperidone palmitate once-every-3-months (PP3M) following treatment with once-monthly paliperidone palmitate (PP1M). Patients and Methods: Data derived from the IBM® MarketScan® Multi-State Medicaid Database were analyzed. Adults aged ≥18 years with ≥1 schizophrenia diagnosis claim and ≥12 months of continuous medical and prescription enrollment before and/or at index date of PP3M were eligible for inclusion. Patients were matched on propensity score to 2 PP3M cohorts: (1) adequately treated (AT), defined as patients treated with PP1M for ≥4 months, with the last 2 doses the same and a PP3M initiation dose meeting the corresponding PP1M-to-PP3M dose conversion, or (2) not adequately treated (NAT), defined as patients who received ≤2 or no PP1M doses. Relapse rates and time to relapse distributions based on the first occurrence of a qualifying event during the 2-year follow-up period were compared between PP3M cohorts using Kaplan-Meier survival curves and log rank test statistics. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Two sensitivity analyses using different matched populations were performed to assess the robustness of the primary findings. Results: Propensity score matching yielded a sample of 1314 patients (657 per group). Most patients were male (68.9%) and aged 25-64 years (90.1%). The relapse rate was significantly lower in the AT (18.4%) versus NAT cohort (26.8%), P = 0.0002. Risk of relapse decreased by 35% for AT versus NAT (HR: 0.65 [95% CI: 0.51-0.81]). Relapse reductions favored the AT cohort in both sensitivity analyses (HR: 0.67 [95% CI: 0.54-0.83] and HR: 0.74 [95% CI: 0.56-0.97]). Conclusion: In this analysis of Medicaid claims data, patients adequately treated with PP1M before transitioning to PP3M demonstrated significantly lower relapse rates and delayed time to relapse.

Real-World Persistence, Maintenance Dosing, and Pre-Post Corticosteroid and Opioid Use Among Crohn's Disease Patients with Prescription Claims for Ustekinumab in the USA.

BACKGROUND: Real-world evidence for how US Crohn's disease (CD) patients use ustekinumab is limited. OBJECTIVES: The aim of this study was to describe the persistence, maintenance dosing, and pre-post corticosteroid and opioid use for CD patients in the USA treated with ustekinumab and those treated with adalimumab as a commonly used descriptive reference product. METHODS: CD patients aged ≥ 18 years with ≥2 CD diagnoses between 1 October 2012 and 31 May 2018 and ≥ 1 new (i.e., no claim for at least 1 year) outpatient pharmacy claim for ustekinumab or adalimumab (first claim date = index date) on or after 26 September 2016 were selected from Symphony Health database. McNemar's tests were used to derive the p-values for pre-post changes in corticosteroid and opioid use within each treatment cohort. RESULTS: A total of 1073 ustekinumab and 2904 adalimumab patients met analysis criteria. Using a 90-day rule for discontinuation, persistence at 1 year post-index was 69.8% for ustekinumab and 65.1% for adalimumab. The majority received doses within ±30% of the approved labeling (ustekinumab 81.1%; adalimumab 78.8%). Doses higher than US package insert (PI) recommended maintenance dose were 7.0% for ustekinumab and 13.6% for adalimumab for 30% above PI, respectively; and 4.0% versus 9.4% for 50% above PI, respectively. Rates of pre-index biologic use suggest that patients treated with ustekinumab may have greater CD severity based on a greater percentage being biologic-experienced (ustekinumab 51.5% and adalimumab 8.4%). From pre- to post-index, the relative proportion of ustekinumab patients with ≥ 1 pharmacy claim for corticosteroids decreased by 25.5% (p < 0.0001) and opioids decreased by 8.4% (p = 0.0030). Results for adalimumab (a commonly used descriptive reference product in CD) showed generally similar trends. CONCLUSIONS: In this real-world study, persistence for ustekinumab remained high at 1 year. The majority of the patients in the ustekinumab cohort followed US PI recommended dosing. The percentage of patients with average dose above PI recommendations over 1 year were low for ustekinumab. Reductions in the proportion of patients with claims for corticosteroids or opioids were observed in patients using ustekinumab.

Efecto Inhibitorio de fracciones polifenolicas de la semilla de Persea americana var. Hass sobre el crecimiento de Helicobacter pylori / Inhibitory effect of seed polyphenolic fractions of Persea americana var. Hass on the Helicobacter pylori growth

ntroducción: El cáncer gástrico (CG) es la principal causa de muerte por cáncer en Colombia y de etiología multifactorial, asociada a factores genéticos del huésped, factores ambientales y el oncopatogeno Helicobacter pylori (H. pylori) como el principal factor de riesgo de la enfermedad. El aguacate (Persea americana var. Hass, (P. americana)) posee un alto contenido de polifenoles, con actividad bactericida, antioxidante, anti-ureasa, y antinflamatoria, que a su vez limitan los cambios en el ambiente gástrico que favorecen la colonización de la bacteria y posterior desencadenamiento de la cascada precancerosa. Objetivo: Evaluar la concentración mínima inhibitoria de fracciones polifenolicas de la semilla de P. americana sobre el crecimiento in vitro de H pylori. Resultados: La evaluación de la concentración mínima inhibitoria (CMI) de las tres fracciones obtenidas de la semilla de P. americana en cultivo de H. pylori in vitro, mostró que las fracciones uno y dos inhibieron el crecimiento bacteriano a 3000 ppm, mientras que la fracción 3 a 1500 ppm, P< 0,05. Conclusión: Se encontraron tres biofracciones polifenolicas de la semilla P. americana, principalmente constituidas por procianidinas, con actividad antibacterial in vitro de Helicobacter pylori, sin embargo, la fracción tres, de mayor peso molecular, inhibió el crecimiento de manera significativa a una CMI de 1500 ppm, comparada con las fracciones uno y dos.

Introduction: Gastric cancer (GC) is the main cause of cancer death in Colombia and of multifactorial etiology, associated with genetic factors of the host, environmental factors and the oncopathogen Helicobacter pylori (H. pylori) as the main risk factor of the disease. The avocado (Persea americana var. Hass, (P. americana)) has a high content of polyphenols, with bactericidal, antioxidant, anti-urease, and anti-inflammatory activity, which in turn limit changes in the gastric environment that favor colonization bacteria and subsequent triggering of the precancerous cascade. Objective: To evaluate the minimum inhibitory concentration of polyphenolic fractions of P. americana seed on the in vitro growth of H pylori. Results: The evaluation of the minimum inhibitory concentration (MIC) of the three fractions obtained from the P. americana seed in H. pylori culture in vitro, showed that fractions one and two inhibited bacterial growth at 3000 ppm, while fraction 3 at 1500 ppm, P <0.05. Conclusion: Three polyphenolic biofractions of the P. americana seed were found, mainly constituted by procyanidins, with in vitro antibacterial activity of Helicobacter pylori, however, fraction three, with a higher molecular weight, significantly inhibited growth at a MIC of 1500 ppm, compared to fractions one and two.

Burden of Crohn's disease in the United States: long-term healthcare and work-loss related costs.

AIMS: To quantify the long-term direct and indirect costs among patients with Crohn's disease (CD) and specific subgroups of these patients in the United States from the private payer's perspective. MATERIALS AND METHODS: This retrospective study used the OptumHealth Care Solutions, Inc database (01 January 1999-31 March 2017) to match (1:5) adult patients with ≥2 claims for CD to patients without inflammatory bowel disease (IBD). Patterns observed during follow-up (i.e. biologics, opioids, or steroids; CD-related surgery; moderate-to-severe disease; and comorbidities) were used to identify CD subgroups. Comparisons of healthcare resource utilization, work loss days, and direct and indirect work loss-related costs were made between matched cohorts. Descriptive analyses of costs were conducted within each CD subgroup. RESULTS: There were 6,715 and 33,575 patients in the CD and non-IBD cohorts, respectively. The direct burden was significantly higher in the CD cohort compared to the non-IBD cohort, with 0.34 inpatient admissions per patient per year (PPPY) versus 0.12 (217% increase; p < .001), and $24,500 direct healthcare costs PPPY versus $7,037 ($17,463 increase; p < .001). The trend was similar for the indirect burden, with work loss-related costs PPPY of $5,490 in the CD cohort versus $3,322 in the non-IBD cohort ($2,168 increase; p < .001). The burden was numerically higher in the CD subgroups, with direct healthcare costs reaching $101,013 PPPY in the surgery subgroup. LIMITATIONS: Severity of CD was determined based on claims-based algorithms due to the lack of access to medical files. Absenteeism was imputed based on claims data, and presenteeism was not assessed. CONCLUSIONS: The direct healthcare and indirect work loss-related costs of patients with CD was significantly higher compared to patients without IBD over an average follow-up of 5 years.

Long-term direct and indirect costs of ulcerative colitis in a privately-insured United States population.

Objective: Prior evaluations of ulcerative colitis (UC)-related costs are dated or encompassed limited follow-up. This study assessed the incremental direct and indirect work loss-related costs of privately-insured patients with UC in the United States, overall and in specific subgroups.Methods: In this retrospective matched cohort study, the OptumHealth Care Solutions, Inc (formerly Optum Health Reporting and Insights employer) database (01 January 1999-31 March 2017) was used to identify adult patients with ≥2 claims for UC, who were matched 1:5 to patients with no claims for inflammatory bowel disease (IBD). UC subgroups were identified based on indicators during the observation period (i.e. use of biologics, opioids, or corticosteroids; UC-related surgery; moderate-to-severe disease; UC-related comorbidities). Healthcare resource utilization (HRU), work loss days, and direct and work loss-related costs were compared between matched cohorts. Descriptive analyses of direct and work loss-related costs were conducted within each UC subgroup.Results: Compared to the non-IBD cohort (n = 46,765), the UC cohort (n = 9353) incurred higher HRU, including 128% more inpatients visits, resulting in $11,029 higher direct costs per patient per year (PPPY; $7170 vs. $18,198; p < .001). Patients in the UC cohort also incurred more work loss days, resulting in $2142 higher work loss-related costs PPPY ($3165 vs. $5307; p < .001). Direct and work loss-related costs were particularly high in the UC subgroups, with patients undergoing UC-related surgery incurring the highest costs.Conclusions: Over ∼5 years follow-up, patients with UC had significantly higher all-cause direct healthcare and indirect work loss-related costs compared to matched patients without IBD.

Persistence, Dose Titration, and Health Care Resource Utilization Among Crohn's Disease Patients Treated With Ustekinumab: A Real-World Analysis in the United States.

INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. This real-world study evaluated persistence, dose titration, health care resource utilization (HCRU) and associated costs, and medication use among CD patients treated with ustekinumab (UST) in several pooled US commercial database populations. METHODS: CD patients aged ≥ 18 years with medical or pharmacy claims for UST were selected from pooled data from 3 large, national commercial databases. The first observed medical or pharmacy claim for UST was the index date. Patients were required to have had ≥ 1 medical claim with a CD diagnosis during the 12 months prior to the index date and continuous health plan enrollment for a minimum of 12 months prior to and 12 months after the index date. Comparisons of outcomes during the baseline and follow-up periods were conducted using inferential statistical tests. RESULTS: A total of 214 eligible UST patients were selected. The majority (74.8%) were biologic experienced (mean age: 41 years), and 83.6% remained treatment persistent during the 12-month post-index period. Among discontinuers, 25.7% restarted UST, and 8.6% switched from UST in the 12-month observation period. The mean treatment duration was 329 days. Most patients (77%) used the recommended UST dose, as defined as being within a 20% dose variation from label (90 mg/8 weeks ± 20%), 17.9% experienced dose escalation, and 5.1% experienced dose reduction. Post-index immunomodulator and corticosteroid use reduced by 20% and 28%, respectively, as compared with pre-index use among CD patients using UST. Annual all-cause ER visits and inpatient stays decreased by 20.5% and 30.3%, respectively, with similar downward trends for annual CD-related HCRU. CONCLUSIONS: The majority of CD patients prescribed UST were biologic experienced, and persistence was high over the 1-year follow-up. UST treatment initiation was associated with reductions in ER visits, inpatient stays, and steroid and other medication use.

Real-world evidence on adherence, persistence, switching and dose escalation with biologics in adult inflammatory bowel disease in the United States: A systematic review.

WHAT IS KNOWN AND OBJECTIVE: The application of biologics to treat inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is well established. Our aim was to characterize the most recent five years of data on rates of adherence, persistence, switching and dose escalations with biologics used to treat IBD in the United States. METHODS: We systematically reviewed electronic databases MEDLINE, MEDLINE In-Process, EMBASE and Cochrane Library for 2012-2017 as well as conference proceedings for 2016-2017 published in English. RESULTS AND DISCUSSION: Of 449 records identified, 41 met all screening criteria. Published studies varied greatly in methodology, data sources, population studied, follow-up time and endpoint definitions, preventing meaningful comparisons across studies. Based on studies using a medication possession rate threshold of <80% or <86%, 38%-77% of patients were found non-adherent to biologics. Discontinuation within the first 3 months occurred in 0%-25% of patients in six studies; 7%-65% discontinued by 12 months in 13 studies. Among all patients who initiated an index biologic, the switch rate to another biologic ranged from 4.5% to 20% in 6 studies. Dose escalations were reported in only four studies; 8%-35% of patients had their dose escalated within the first year of therapy. WHAT IS NEW AND CONCLUSION: This study demonstrates variability in study design and methodology to assess adherence, persistence, switching and dose escalation with biologics among adults with IBD in the United States. Our findings suggest that real-world biologic use may be suboptimal and indicate new therapies and/or additional patient support may be needed.