Real-World Characteristics of Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy: An Analysis of Electronic Healthcare Records in the United States.

BACKGROUND: Tafamidis was approved for the treatment of hereditary and wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) in May 2019, based on findings from the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). METHODS: This retrospective cohort study evaluated the factors associated with tafamidis prescription after diagnosis of ATTRwt-CM in the real world. Between May 2019 and December 2020, 430 patients with 6 months' database activity were indexed from the de-identified US Optum electronic healthcare records at first diagnosis of ATTRwt-CM or prescription of tafamidis, then followed until last activity or death. Of these, 209 patients were prescribed tafamidis during follow-up, 167 (80%) within 1 month, 98% by 6 months, and 100% by 9 months. Median time from index to tafamidis prescription, calculated using the Kaplan-Meier method, was 5.8 months (95% confidence interval [CI] 2.4-not evaluable). RESULTS: Factors associated with tafamidis prescription in a multivariable Cox proportional hazards regression (hazard ratio [95% CI]) included age ≥ 65 years (2.1 [1.07-4.05]), male sex (1.6 [1.07-2.28]), having heart failure/cardiomyopathy (2.4 [1.54-3.82]), and having had technetium-99m pyrophosphate myocardial scintigraphy (1.7 [1.28-2.28]). CONCLUSIONS: The clinical characteristics of patients with ATTRwt-CM who were prescribed tafamidis in the real world were broadly comparable with those who took part in ATTR-ACT. Further studies are needed to evaluate hereditary and ATTRwt-CM patient populations in the real world and assess the long-term outcomes associated with disease management pathways. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT01994889.

Persistence with daily growth hormone among children and adolescents with growth hormone deficiency in the UK.

Background: Children with growth hormone deficiency (GHD) are treated with daily somatropin injections; however, poor treatment persistence and adherence have been recognized previously and have been shown to negatively impact growth outcomes. A recent real-world study of a US pediatric GHD population found that a substantial proportion of children discontinued somatropin therapy, but similar data for a real-world UK population are lacking. Objectives: To describe the discontinuation of, and persistence with, daily somatropin treatment among children with GHD in the UK. Methods: This was a retrospective cohort study of children (≥3 and <16 years old) with ≥1 medication prescription for daily injectable somatropin from 1 July 2000 to 31 December 2020 in the IQVIA Medical Research DATA (IMRD) database. Early persistence was defined as the proportion of children prescribed ≥1 somatropin refill (≥2 prescriptions). Discontinuation was defined as the first date at which a medication gap for somatropin (of >60 or >90 days between prescriptions) occurred. Kaplan-Meier methods were used to evaluate persistence (non-discontinuation) over time to assess time to first discontinuation event. Cox proportional hazards models were used to evaluate the relationship between patient characteristics and time to medication discontinuation. Results: Among the cohort identified in this study (n = 117), the majority (n = 84, 71.8%) had 48 months of available follow-up; 56.4% were boys and the mean (median) age was 8.6 (8.0) years. About 98% exhibited early persistence, but persistence over the follow-up period decreased with follow-up duration. Using the conservative 90-day gap definition of persistence, an estimated 72.4%, 52.8%, and 43.3% were persistent at 12, 36, and 48 months. Lower persistence rates were observed using the 60-day definition. No significant patient predictors of time to discontinuation were identified. Conclusions: Despite high early persistence with somatropin, a high percentage of children with GHD were increasingly non-persistent over time. More than 1 in 4 were non-persistent at 12 months and more than 1 in 2 were non-persistent at 48 months of follow-up. These results suggest that strategies to support improved medication-taking behavior among children with GHD in the UK are warranted.

Baseline characteristics and secondary medication adherence among Medicare patients diagnosed with transthyretin amyloid cardiomyopathy and/or receiving tafamidis prescriptions: A retrospective analysis of a Medicare cohort.

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed, life-threatening condition that mostly affects older persons. In May 2019, regulatory approval of tafamidis provided the first pharmacologic treatment of ATTR-CM. In the pivotal phase 3 Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT), 97.2% of patients were classified as adherent (defined as taking ≥ 80% of scheduled doses). Given its recent approval, there is limited real-world evidence examining patient adherence to tafamidis. OBJECTIVE: To evaluate adherence patterns, demographics, and clinical characteristics of patients in the United States receiving tafamidis prescriptions through Medicare. Secondarily, we aimed to evaluate concomitant medications filled by this patient population. METHODS: We conducted a retrospective cohort study of US Medicare claims data, limited by the Health Insurance Portability and Accountability Act of 1996, in adult patients with an adjudicated pharmacy claim for tafamidis (tafamidis free acid 61-mg capsule once daily or tafamidis meglumine four 20-mg capsules once daily) between May 1, 2019, and June 30, 2021. Gaps in therapy were measured using day gaps between prescription refills and continuous measure of medication gaps. Implementation adherence was assessed through modified medication possession ratio (MPRm), medication refill adherence (MRA), and proportion of days covered (PDC). Patients were grouped based on Medicare coverage. Patients were analyzed by subgroups based on age and at the zip code level, via distressed communities index quartiles and rural-urban tiers. RESULTS: A total of 3,558 patients who received a prescription fill of a tafamidis formulation were identified using Medicare Fee-for-Service (FFS) and Medicare Advantage (MA) claims data from May 1, 2019, to June 30, 2021. The characteristics of this patient population were consistent with published literature, as 98.6% were older than 65 years, 53.4% were between 75 years and 84 years, and 81.5% were male. In the patient population receiving tafamidis refills, adherence was high across all 3 measures, with mean MPRm greater than 90% and mean MRA greater than 80%, across all age groups. Mean PDC adherence rates were 79% or more across all age groups. Concomitant medications were generally indicated for heart failure and thrombosis. Among monotherapy groups with similar demographic makeup, adherence was significantly higher among users of tafamidis free acid vs tafamidis meglumine (P < 0.0001 across all mean adherence measures). CONCLUSIONS: Our results demonstrate that real-world adherence to tafamidis in the Medicare population is high, regardless of age, zip code-level socioeconomic quartile, or geography. Adherence was higher among patients receiving tafamidis free acid, suggesting that the enhanced convenience of a single capsule once daily may positively contribute to adherence among patients with ATTR-CM. DISCLOSURES: Darrin Benjumea is an employee of Genesis Research who has been contracted by Pfizer, Inc., for involvement in this study. Andrew Peterson is an employee of University of the Sciences who has been contracted by Pfizer, Inc., for involvement in this study. Zach Bredl is an employee of Care Journey who has been contracted by Pfizer, Inc., for involvement in this study. Anuja Roy, Nick Marchant, Jose Alvir, Rahul Bhambri, Jason Kemner, and Bhash Parasuraman are employees of Pfizer, Inc., and own stock and/or stock options. This study was supported by Pfizer, Inc.

Baseline Characteristics and Secondary Medication Adherence Patterns Among Patients Receiving Tafamidis Prescriptions: A Retrospective Analysis Using a National Specialty Pharmacy Dispensing Database.

Introduction: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a serious, underrecognized condition, which leads to heart failure and early mortality if left untreated. Until recently, heart transplantation was the only treatment for ATTR-CM. Regulatory approval of tafamidis transformed treatment for patients. In the phase 3 Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT), which established the safety and efficacy of tafamidis, medication adherence was high with 97.2% of patients taking ≥80% of scheduled doses. Evidence of real-world adherence to cardiology drugs demonstrates low adherence and suboptimal outcomes; however, real-world adherence to tafamidis has not been investigated. The main objective of this study was to describe adherence patterns of patients filling tafamidis in the Symphony Health database. Methods: This retrospective analysis of the Symphony Health Solutions claims database used secondary adherence measures, including modified medication possession ratio (MPRm), days between fills adherence rate, and compliance rate, to assess adherence patterns of 2020 patients filling tafamidis free acid 61-mg capsules or tafamidis meglumine 4x20-mg capsules from June 1, 2019 to August 31, 2020. Results: Patients receiving a tafamidis formulation had characteristics consistent with the expected patient population; 71.6% were aged 75-84 years, 83.2% were male, and the highest proportion resided in the Northeast region (30.5%) of the United States. Adherence for tafamidis was high, as 75% to 100% of the patients across subgroups met or exceeded the commonly defined adherence threshold of 80%. Median number of refills ordered and received was six refills per patient. Most patients received refills with no gap (n=1633) or a gap <30 days (n=1267/1317 patients). Adherence was high across follow-up time, sex, and age subgroups. Adherence varied by geographic region, with the Northeast being significantly higher than the Midwest (mean MPRm 94.41% vs 88.21%, p=0.0007). Conclusion: These results provide evidence that real-world adherence to tafamidis in patients with ATTR-CM is high.

A Systematic Review of Household and Family Alcohol Use and Adolescent Behavioural Outcomes in Low- and Middle-Income Countries.

Exposure to alcohol misuse is considered an adverse childhood experience impacting on neurodevelopmental and behavioural outcomes in adolescents including substance use, mental illness, problem behaviours, suicidality, and teenage pregnancy. Most research on this issue has focussed on higher income countries, whereas patterns of alcohol use and related factors may be different in low- and middle-income countries (LMICs). This systematic review therefore seeks to collate all published studies from 1990-2020 on the topic set in LMICs. 43 studies were included, totalling 70,609 participants from 18 LMICs. Outcomes assessed included: substance use; depression/anxiety; suicidal ideation; problem behaviour; emotional dysfunction; teenage pregnancy; and self-harm. Despite heterogeneity in the studies identified, this review documented some association between exposure to household alcohol misuse and adverse adolescent outcomes in LMICs, including mental health problems, problem behaviours, and suicidality. The mechanisms leading to these outcomes are likely varied, and further research in different socio-economic and cultural contexts, particularly in the form of longitudinal studies, is called for.

A Systematic Review of Household and Family Alcohol Use and Childhood Neurodevelopmental Outcomes in Low- and Middle-Income Countries.

Childhood exposure to alcohol misuse by household adults has been related to childhood developmental delay, cognitive impacts, mental illness, and problem behaviours. Most evidence comes from high income countries. This systematic review only included studies from low- and middle-income countries (LMICs). Five databases were searched from 1990-2020. Twenty-eight studies of children 0-12 years were included, with 42,599 participants from 11 LMICs. The most common outcome was behavioural problems/disorders (19 studies). Despite varying study designs, this review found that alcohol misuse by household members in LMICs is associated with adverse child neurodevelopmental outcomes, although casual inferences cannot be drawn in the absence of well conducted prospective studies. Statistically significant correlations were described between parental alcohol misuse and child emotional and behavioural difficulties, cognitive delay, and risky behaviours. In future, prospective cohort studies are recommended, with adjustment for confounders.

The Burden of Bloodstream Infections due to Stenotrophomonas Maltophilia in the United States: A Large, Retrospective Database Study.

BACKGROUND: Stenotrophomonas maltophilia is an opportunistic pathogen observed in both nosocomial and community-onset infections. S. maltophilia is intrinsically resistant to many currently available broad-spectrum antibiotics and is often not included in antimicrobial resistance surveillance studies or stewardship programs' guidelines. METHODS: A retrospective cohort study of patients with S. maltophilia bloodstream infection (BSI) in the United States was conducted using the 2010-2015 US Premier Healthcare Database. This study described patient characteristics, infection characteristics, antibiotic treatment, and discharge status. RESULTS: S. maltophilia was the most common carbapenem-resistant, gram-negative pathogen causing BSIs in this database. Of 486 unique patients with S. maltophilia BSI, 44.6% were assessed as community-onset, 95% of cultures were susceptible to trimethoprim-sulfamethoxazole (TMP-SMX), and 84% were susceptible to fluoroquinolones; 39.1% of patients received a potentially effective antibiotic (fluoroquinolone, doxycycline, ceftazidime, minocycline, or TMP-SMX) during the empiric treatment period (≤3 days post-index culture date), whereas 85.8% received a potential effective antibiotics during the definitive treatment period. The most common antibiotic received as definitive treatment was levofloxacin (48.9%). TMP-SMX was used infrequently empirically (10.5%) and in 38.3% during the definitive period. Compared with BSIs caused by other carbapenem-resistant gram-negative pathogens, S. maltophilia BSIs were more likely to be community-onset, and were more likely to be discharged to home and to have a lower mortality rate. CONCLUSIONS: This study demonstrated that patients at risk for S. maltophilia BSI are highly variable and that standard of care is not clearly defined, leading to questions regarding the appropriateness of antibiotic treatment among patients. Further efforts are needed to better recognize and treat S. maltophilia BSI.