Documentation of asthma control and severity in pediatrics: analysis of national office-based visits.

Objective: To evaluate the extent of documentation of asthma control and severity and associated characteristics among pediatric asthma patients in office-based settings. Methods: This cross-sectional study utilized data from the 2012-2015 National Ambulatory Medical Care Survey (NAMCS). Patients aged 6-17 years with a diagnosis of asthma were included. Weighted descriptive analysis examined the extent of documentation and uncontrolled asthma; while logistic regression evaluated associated characteristics. Results: Overall, there were 2.47 million (95% confidence interval, 95% CI: 2.04-2.90) average annual visits with asthma as a primary diagnosis. Asthma control and severity was documented in only 36.1% and 33.8% of the visits, respectively. An established patient (odds ratio, OR = 3.81), Hispanic ethnicity (OR = 2.10), chronic sinusitis (OR = 5.59), and visits in the Northeast (OR = 2.12) and Midwest (OR = 2.25) regions had higher odds of documented asthma control status, whereas undocumented asthma severity (OR = 0.02), and visits in spring (OR = 0.34), had lower odds. Osteopathic doctors (OR = 0.18), visits in the Northeast region (OR = 0.23), chronic sinusitis (OR = 0.08), and undocumented asthma control status (OR = 0.03) had lower odds of documented asthma severity, whereas visits in spring (OR = 3.88) and autumn (OR = 3.32) had higher odds. Moderate/severe persistent asthma (OR = 15.35) had higher odds of uncontrolled asthma (as compared to intermittent asthma), while visits in the summer (OR = 0.14) had lower odds. Conclusion: The findings of this study suggest a critical need to increase the documentation of asthma severity and control to improve quality of asthma care in children.

Healthcare resource utilization, expenditures, and productivity in patients with asthma with and without allergies.

Objective: To compare healthcare resource utilization (HCRU), healthcare expenditures, and work productivity and activity impairment within a general asthma population with persistent asthma and evidence of allergy (PA-EA) and persistent asthma with no evidence of allergy (PA-NEA).Methods: We conducted a retrospective analysis of survey responses and claims from the Observational Study of Asthma Control and Outcomes (OSACO) study. Eligible patients with persistent asthma aged ≥12 years were sent four surveys over 15 months. Regression models were used to assess the association between: (1) PA-EA (defined as a positive response to a survey question about hay fever/seasonal allergies AND ≥1 diagnostic code for atopic conditions) and HCRU and expenditures; and (2) PA-EA and Work Productivity and Activity Impairment (WPAI)-Asthma questionnaire scores (vs. PA-NEA).Results: Adjusted data showed that, vs. PA-NEA (n = 312), patients with PA-EA (n = 971) incurred 1.34-times more all-cause prescriptions (95% confidence interval [CI], 1.20-1.48), $132.79 higher prescription costs (95% CI, $22.03-243.56), and $926.11 higher all-cause total healthcare costs (95% CI, $279.67-1572.54), per 4-month period. Patients with PA-EA were 4.1% less productive while working (95% CI, 3.75-4.48%) and experienced a 6.5% reduction in all activities (95% CI, 6.11-6.88%) vs. those with PA-NEA.Conclusions: Patients with PA-EA had greater HCRU, healthcare expenditures, and lower productivity compared with those patients with PA-NEA. These results highlight the burden of atopy in patients with persistent asthma and underscore the importance of allergic endotype identification for more vigilant disease management.

Impact of allergies on health-related quality of life in patients with asthma.

Objective: To estimate the health-related quality of life (HRQoL) and health utilities among asthma patients with and without comorbid allergies in a managed care population.Methods: This was a retrospective analysis of patient survey responses and pharmacy claims from the Observational Study of Asthma Control and Outcomes (OSACO). Patients ≥12 years-old with persistent asthma received four identical surveys between April-2011 and December-2012. The presence of allergy was identified by a positive response to a survey question about hay fever/seasonal allergies and ≥1 diagnosis-related ICD-9-CM code(s) for allergic conditions. HRQoL instruments included generic utility (EQ-5D-3L [including VAS]), asthma-specific utility (AQL-5D) and asthma-specific health status (Mini Asthma Quality of Life Questionnaire [MiniAQLQ]). Median regression was used for utility scores and Least Squares regression for MiniAQLQ, adjusting for sociodemographic characteristics and smoking.Results: Of the 2681 asthmatics who completed the first survey in the OSACO study, 971 had comorbid allergies. After adjusting for covariates, asthma patients with comorbid allergies had significantly lower MiniAQLQ scores than patients without allergies (-0.489 [95% CI -0.570, -0.409]; p < 0.01), with the greatest decrement/impairment observed for the environmental stimuli domain (-0.729 [95% CI -0.844, -0.613]; p < 0.01). Utility scores were also statistically significantly lower for asthma patients with comorbid allergies compared to those without allergies (EQ-5D, -0.031 [95% CI -0.047, -0.015]; AQL-5D, -0.036 [95% CI -0.042, -0.029]; p < 0.01 each).Conclusions: The presence of allergies with persistent asthma is associated with a significant deleterious impact on several different measures of HRQoL.

Perspectives on Living with Chronic Spontaneous Urticaria: From Onset through Diagnosis and Disease Management in the US.

Chronic spontaneous urticaria is challenging to manage and substantially affects quality of life. This US, non-interventional qualitative study examined patients' clinical journeys and emotional burden from symptom onset through disease management. Chronic spontaneous urticaria patients participated in interviews and completed diaries focusing on disease and treatment history/perspectives, impact on personal/family life, and relationships with physicians/other healthcare providers. Physicians were interviewed about their views on disease management and patient care. Twenty-five patients, previously or currently receiving chronic spontaneous urticaria treatment(s), and 12 physicians participated. Key stages following symptom onset were identified: Crisis (associated with feelings of torment/disorientation/shock); Searching for answers (puzzlement/frustration/anxiety); Diagnosis (relief/satisfaction/fear/isolation); and Disease management (frustration/hope/powerlessness). Findings revealed patients' perceptions and experiences of chronic spontaneous urticaria, including living with a 'skinemy', experiencing their 'own personal hell' and feeling 'like an experiment'. Awareness of unmet needs in patient care/management identified in this study may ultimately improve patient support and enhance physicians' understanding of disease burden.

Long-term omalizumab outcomes in chronic idiopathic urticaria: a real-world study.

Background: Although clinical trials documented omalizumab's efficacy in U.S. patients with chronic idiopathic urticaria (CIU), the real-world evidence on its long-term effectiveness is lacking. Objective: To assess omalizumab use and the long-term response in a large sample of U.S. real-world patients. Methods: Patients with CIU and ≥ 12 years old who were initiated on omalizumab (index date) and with ≥ 6 months of postindex data were identified in an electronic medical record system (2007-2018). Omalizumab use was described. Provider assessments of disease control and course, and patient-reported symptoms were compared at 6-month intervals postindex versus baseline in the patients with values available at both time points. Results: A total of 1096 patients (mean age, 44.1 years; 74.7% women) were followed up for a mean of 19 months postindex. Patients, predominantly initiated on a 300-mg dose, received a mean of 15 omalizumab administrations and were treated continuously for a mean of 14.2 months. At 6 months postindex versus baseline, the patients (n = 708) were more likely to be well controlled (odds ratio [OR] 31.68 [95% confidence interval {CI}, 17.20-58.36]) with an improved disease course (OR 15.73 [95% CI, 11.33-21.85]). Moreover, the patients (n = 373) were less likely to report itching (OR 0.39 [95% CI, 0.21-0.76]), rash (OR 0.59 [95% CI, 0.45-0.78]), and swelling (OR 0.46 [95% CI, 0.36-0.59]). Benefits associated with omalizumab treatment were sustained through month 24 and beyond. Conclusion: This real-world study showed that the patients who received a mean of 15 omalizumab administrations over a mean of 14.2 months experienced, starting at 6 and through 24 months after omalizumab initiation and beyond, improved CIU control, course, and symptoms.

Medication use and indicators of poor asthma control in patients with and without allergies.

Background: Approximately two-thirds of people with asthma have some evidence of allergy; their condition differs from nonallergic asthma in terms of predominant symptoms and clinical outcomes. Objective: To compare asthma control and medication use among patients with persistent asthma with evidence of allergy (PA-EA) and patients with persistent asthma with no evidence of allergy (PA-NEA). Methods: A retrospective analysis of survey responses and medication claims data from the Observational Study of Asthma Control and Outcomes study, a prospective survey linked to retrospective claims-based analysis of patients ages ≥ 12 years with persistent asthma in a U.S. health maintenance organization. Evidence of allergy was defined as both a positive response to a survey question about hay fever and/or seasonal allergies and one or more medical diagnostic codes for atopic conditions. Regression models were used to compare asthma control (Asthma Control Questionnaire [ACQ] scores) and asthma medication use between PA-EA and PA-NEA. Results: Adjusted data showed that, versus the patients with PA-NEA (n = 312), patients with PA-EA (n = 971) had higher (worse) 5-item and 6-item ACQ (ACQ-5 and ACQ-6) scores (by 0.34 [95% confidence interval {CI}, 0.24-0.44]; and 0.31 [95% CI, 0.21-0.40], respectively), were more likely to have poorly controlled asthma (ACQ-5 score ≥ 1.5: odds ratio 3.37 [95% CI, 2.07-5.50]; ACQ-6 score ≥ 1.5: odds ratio 3.46 [95% CI, 2.13-5.62]) and less likely to have well-controlled asthma (ACQ-5 score ≤ 0.75: odds ratio 0.21 [95% CI, 0.13-0.34]; ACQ-6 score ≤ 0.75: odds ratio 0.21 [95% CI, 0.13-0.35]). Patients with PA-EA also had greater asthma medication use, most notably 2.5 times more prescriptions of high-dose inhaled corticosteroid in a 4-month period (95% CI, 1.21-5.16) and 16.15 times higher odds of chronic oral corticosteroid use (95% CI, 1.50-174.09) versus PA-NEA. Conclusion: The patients with PA-EA versus PA-NEA had worse asthma control and greater medication use. These patients may need more vigilant clinical oversight and treatment management to ensure adequate asthma control.

Asthma control and disease burden in patients with asthma and allergic comorbidities.

OBJECTIVE: To assess asthma control and associations with health-related quality of life (HRQoL) and economic outcomes among patients with asthma and allergic comorbidities treated with inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) combination therapy. METHODS: Data from the 2011-2013 US National Health and Wellness Survey were used to identify patients with asthma currently treated with ICS and LABA combination therapy (N = 1923). Patients were included if they self-reported a physician diagnosis of asthma and at least one allergic/asthma-related comorbid condition (e.g., nasal allergies, atopic dermatitis). Asthma Control Test scores categorized patients as very poorly (scores ≤ 15; 29.3%), not well (16-19; 25.1%), or well controlled (20-25; 45.7%). Outcomes included HRQoL (SF-36v2; SF-12v2), work productivity and activity impairment, healthcare utilization (HRU), and annual indirect and direct costs. Generalized linear models, controlling for covariates, examined whether outcomes differed by asthma control. RESULTS: Over half of the patients had very poorly or not well-controlled asthma (54.4%). Patients with very poorly controlled versus well-controlled asthma reported significantly greater decreases in HRQoL, greater overall work impairment, and higher HRU (all, p < 0.05). Very poorly controlled patients incurred over double the indirect costs and nearly one and a half times the direct and total costs of well-controlled patients. CONCLUSIONS: Increasing level of asthma control was related to improved HRQoL and lower costs. The considerably high prevalence of uncontrolled asthma among patients on ICS and LABA suggests poor treatment adherence or unmet needs in current treatment and may require step-up therapy in appropriate patients according to clinical guidelines.

Health care burden and treatment patterns in commercially insured children with chronic idiopathic/spontaneous urticaria: A real-world study in the United States.

BACKGROUND: Chronic idiopathic urticaria (CIU)/spontaneous urticaria (CSU) is defined by the presence of wheals, angioedema, or both for ≥6 weeks, with or without an identifiable trigger. Real-world health care data among children with CIU/CSU remain scarce. OBJECTIVES: To describe treatment patterns, health care resource utilization (HRU), and costs in pediatric patients with CIU/CSU (<12 years old) and to compare these with pediatric patients without CIU/CSU. METHODS: A commercial administrative claims data base (September 2013 to June 2016) was used. The CIU/CSU cohort included pediatric patients with either two or more claims for a diagnosis of urticaria ≥6 weeks apart or one or more claims for a diagnosis of urticaria and one or more claims for a diagnosis of angioedema ≥6 weeks apart (index was defined as the first claim). The control cohort comprised pediatric patients without urticaria or angioedema (index randomly assigned). Patients with <6 months of eligibility before and after the index date were excluded. HRU and costs were compared between the cohorts during the observation period after propensity score matching. RESULTS: A total of 6109 pediatric patients with CIU/CSU were selected, and 6107 were 1:1 matched with controls. The patients with CIU/CSU who had a mean ± standard deviation age of 4.58 ± 3.36 years, and 47.9% were girls. CIU/CSU-related medication use increased after diagnosis (e.g., baseline versus 6-month follow-up, 2.2 versus 8.0% for nonsedating prescription H1 antihistamines; 7.4 versus 17.4% for oral corticosteroids). Relative to the controls, the patients with CIU/CSU had higher rates of HRU (incidence rate ratios of 1.71, 2.39, and 2.07 for inpatient, emergency department, and outpatient visits, respectively; all p < 0.01), and higher all-cause per patient per year costs (mean cost differences of $2090, $1606, and $483 for total, medical, and pharmacy costs, respectively; all p < 0.01). CONCLUSION: This study highlighted unmet needs in pediatric patients with CIU/CSU who had increased medication (e.g., oral corticosteroids) and HRU burden after a diagnosis for CIU/CSU, and higher rates of HRU and costs relative to those without CIU/CSU.

Asthma control, lung function, symptoms, and corticosteroid sparing after omalizumab initiation in patients with allergic asthma.

BACKGROUND: Omalizumab is approved in patients with moderate-to-severe allergic asthma with symptoms uncontrolled, despite the mainstay therapy. OBJECTIVE: Electronic medical records (EMR) were used to increase the knowledge of omalizumab effectiveness in a real-world setting. METHODS: Patients with uncontrolled moderate-to-severe allergic asthma, ages ≥12 years old, initiated on omalizumab (index date), with ≥12 months of pre- and postindex data, were identified in an EMR data base. An Asthma Control Test score (≥20 is considered well controlled), forced expiratory volume in 1 second as a percentage of the predicted value (<80% considered below normal), symptoms, and oral corticosteroid (OCS) and inhaled corticosteroid (ICS) use were compared in the 12-month post- versus the preindex period with univariate generalized estimating equations adjusted for repeated measurements. RESULTS: A total of 208 patients (mean ± standard deviation[SD] age, 41 ± 19 years; 64.9% women; 71.2% white; and with a mean ± SD serum total immunoglobulin E level of 455.4 ± 644.7 IU/mL) were identified. In the post- versus preindex period, the patients were significantly more likely to have well-controlled asthma (odds ratio [OR] 1.72 [95% confidence interval {CI}, 1.11-2.64]) and less likely to have a lung function value below normal (nonsignificant) after omalizumab initiation. The patients experienced significantly less coughing (OR 0.66 [95% CI, 0.49-0.91]), shortness of breath (OR 0.60 [95% CI, 0.44-0.83]), and wheezing (OR 0.59 [95% CI, 0.43-0.81]), with no improvement in chest tightness. A significantly lower likelihood of new OCS prescriptions (OR 0.58 [95% CI, 0.41-0.82]) was observed. A lower likelihood of new high- and medium-dose ICS prescriptions was nonsignificant. CONCLUSION: Omalizumab was associated with beneficial effects on asthma control and symptoms, and the likelihood of requiring new OCS prescriptions. An observed trend of improved lung function and lower likelihood of requiring high- and medium-dose ICS did not reach statistical significance.

Real-world use of omalizumab in patients with chronic idiopathic/spontaneous urticaria in the United States.

BACKGROUND: Omalizumab was approved for the treatment of chronic idiopathic urticaria (CIU)/chronic spontaneous urticaria (CSU) in the United States in March 2014. OBJECTIVE: This study sought to describe real-world omalizumab use, in the United States, in a large cohort of patients with CIU/CSU. METHODS: Patients with CIU/CSU (ages ≥12 years) initiated on omalizumab (index date) with ≥12 months of pre- and postindex data were identified in the an insurance claims data base (January 1, 2013, to July 31, 2016). Treatment patterns, including the dosing regimen and continuous use of omalizumab (no gaps for ≥60 days), were described during the 12-month postindex follow-up period. RESULTS: A total of 1546 patients (mean ± standard deviation [SD] ages, 44 ± 14.5 years; 73.1% women) were identified. Most of the patients (84.5%) were initiated on omalizumab 300-mg dose; 90% maintained the initial dose, 7.5% had a dose increase, and 4.6% had a dose decrease. The mean ± SD omalizumab treatment duration was 9.1 ± 3.8 months, the mean ± SD number of omalizumab administrations was 8.3 ± 4.8, and the mean ± SD administration frequency was 44 ± 29 days. A proportion of the patients continuously treated with omalizumab for 6, 9, and 12 months was 67.3, 54.8, and 47.4%, respectively. Among the patients who discontinued omalizumab for ≥3 months (39.8%), 21% restarted the treatment after a mean ± SD of 4.4 ± 1.3 months. The proportion of patients who used other CIU/CSU-related medications decreased pre- to postindex (94.8 to 81.1%), with the highest decrease observed in oral corticosteroids (75.7 to 49.9%). CONCLUSION: In this large real-world study, the majority of the patients with CIU/CSU were initiated on a 300-mg omalizumab dose and treated without titration up or down for 9 months on average. Most of the patients were continuously treated with omalizumab for ≥6 months, and one-fourth of the patients who discontinued treatment resumed it. Moreover, compared with baseline levels, the use of other CIU/CSU-related medications was lower after omalizumab initiation, with the most prominent decrease observed in oral corticosteroids.

The national cost of asthma among school-aged children in the United States.

BACKGROUND: Recent research has quantified the national health care resource use (HCRU) and health care expenditure (HCE) burden associated with adult asthma; however, estimates specific to school-aged children are more than 2 decades old. OBJECTIVE: To estimate the national HCRU and HCEs attributable to asthma among school-aged children in the United States. METHODS: This was a cross-sectional retrospective analysis of school-aged children (aged 6-17 years) in the nationally representative 2007-2013 Medical Expenditure Panel Survey. All-cause HCRU and HCEs of school-aged children with asthma were compared with school-aged children without asthma, controlling for sociodemographics and comorbidities. HCRU encounters included emergency department (ED) and outpatient visits, hospitalizations, and prescriptions. Expenditures included total, medical, ED, inpatient, outpatient, and pharmacy. Negative binomial regression analyses were used for HCRU and Heckman selection with logarithmic transformation, and smearing retransformation was used for HCEs. RESULTS: There were 44,320 school-aged children of whom 5,890 had asthma. Children with asthma incurred a higher rate of all-cause annual ED visits (incidence rate ratio [IRR], 1.5; P < .001), hospitalizations (IRR, 1.4; P < .05), outpatient visits (IRR, 1.4; P < .001), and prescription drugs (IRR, 3.3; P < .001) compared with school-aged children without asthma. They incurred US$847 (2015 dollars) more annually in all-cause expenditures (P < .001). Private insurance and Medicaid paid the largest share of expenditures. Pharmacy and outpatient costs represented the largest proportion of total expenditures. On the basis of the nationally representative Medical Expenditure Panel Survey sample weights from 2013, the total annual HCEs attributable to asthma for school-aged children in the United States was US$5.92 billion (2015 dollars). CONCLUSION: Childhood asthma continues to represent a prevalent and significant clinical and economic burden in the United States. More aggressive treatment and asthma management programs are needed to address this national financial and resource burden.

Indicators of poorly controlled asthma and health-related quality of life among school-age children in the United States.

BACKGROUND: Poorly controlled asthma has far-reaching effects on school-age children and their parents, but little is known about the national impact on health-related quality of life (HRQoL). OBJECTIVE: To examine HRQoL associated with asthma and indicators of poorly controlled asthma in the United States. METHODS: This was a cross-sectional analysis of HRQoL among school-age children (age range, 6-17 years) with asthma in the nationally representative 2007-2013 Medical Expenditure Panel Survey (MEPS). Indicators of poor asthma control included the following: exacerbation in the previous 12 months, use of more than three canisters of short-acting beta agonist in 3 months, and annual asthma-specific emergency department or inpatient visits. Health status and HRQoL instruments included the following: the Columbia Impairment Scale (CIS), Child Health Questionnaire (CHQ), Children with Special Health Care Needs Screener (CSHCN), and self-perceived physical and mental health. Ordered logistic regression was used for ordered categorical variables, and logistic regression was used for binary variables. All regressions controlled for sociodemographics and other covariates. RESULTS: There were 44,320 school-age children in the MEPS, of whom 5890 had asthma. School-age children with indicators of poorly controlled asthma had higher odds of feeling unhappy and/or sad or nervous and/or afraid, and of having problems with sports and/or hobbies and schoolwork on the CIS. Results from the CHQ showed that parents of school-age children with asthma and indicators of poorly controlled asthma had higher odds of worrying about their child's health and future. Results from the CSHCN showed that school-age children with asthma and indicators of poorly controlled asthma were more likely to have special health care needs. School-age children with asthma and indicators of poorly controlled asthma had higher odds of having poor perceived physical health. CONCLUSION: This nationally representative study provided novel information on the burden of poorly controlled asthma on emotional problems, school-related and activity limitations, general health status, and worry among school-age children and their families as measured by validated instruments.

Efficacy and safety of omalizumab in children and adolescents with moderate-to-severe asthma: A systematic literature review.

BACKGROUND: There are limited pediatric data about the use of omalizumab, especially the effectiveness and safety of omalizumab in the real-world management of allergic asthma. OBJECTIVE: The objective of this study was to summarize the safety and efficacy of omalizumab in both randomized clinical trials (RCT) used for U.S. Food and Drug Administration registration and real-world studies (RWS) based on clinical care of children with moderate-to-severe asthma. METHODS: Studies that evaluated omalizumab use in patients <18 years old and with asthma, published between January 2003 and October 2016, were retrieved from medical literature data bases. Assessed outcomes included the following: exacerbation rates, spirometric indices, changes in asthma medication use, asthma control, patient-reported outcomes, and health care resource utilization. RESULTS: A total of five RWS were identified; outcomes reported were compared with three omalizumab RCTs. Overall, the mean rate of annual exacerbations was significantly lower after 6 months to 2 years of treatment with omalizumab in both RCTs and RWS. In two RCTs and three RWS, inhaled corticosteroid use was significantly reduced in patients who used omalizumab. Similar reductions in the use of rescue medication were also observed in the RCTs and RWS on omalizumab. Real-world evidence demonstrated improvement in forced expiratory volume in the first second of expiration (% predicted) in patients treated with omalizumab as well as significant improvement in the level of asthma control observed over 1 year. There also was evidence that omalizumab treatment reduced health care resource utilization, including fewer hospitalizations, emergency department visits, and unscheduled medical visits. Safety outcomes in all five RWS showed no new safety signals and demonstrated that omalizumab was well tolerated. CONCLUSION: Overall, RCT evidence strongly supported omalizumab efficacy and safety as add-on treatment in children 6 to 11 years old with moderate-to-severe persistent allergic asthma. RWS data confirmed these findings in an extended patient population of children and adolescents that is more generalizable to the actual day-to-day management of these patients.

Timing of NTRK Gene Fusion Testing and Treatment Modifications Following TRK Fusion Status Among US Oncologists Treating TRK Fusion Cancer.

BACKGROUND: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers with an estimated prevalence of less than 1% across all solid tumors. Tropomyosin receptor kinase inhibitors (TRKis) block the constitutively activated tyrosine receptor kinase (TRK) fusion protein produced in NTRK gene fusion positive (NTRK+) tumors from downstream signaling. Tropomyosin receptor kinase inhibitors are now first-line (1L) or subsequent treatment options for TRK fusion cancers. OBJECTIVE: This study assessed timing of NTRK gene fusion testing and treatment modifications among patients with TRK fusion cancers. PATIENTS AND METHODS: This was a one-time physician questionnaire with a retrospective, multisite patient chart abstraction of oncology practices in the USA. From June to September 2020, medical oncologists from the Oncology Provider Extended Network (OPEN) who treated patients with NTRK+ advanced/metastatic solid tumors abstracted information into electronic case report forms (eCRFs) for adult patients with advanced/metastatic solid tumors and a NTRK+ tumor test result with a known fusion partner. Use of NTRK testing in routine clinical practice among patients with advanced/metastatic solid tumors was assessed. Data included demographic, clinical, and NTRK gene fusion testing characteristics. Responses were summarized using descriptive statistics. RESULTS: Twenty-eight community-based medical oncologists who had managed or treated 148 patients with advanced/metastatic TRK fusion cancer between 01/01/2016 and 12/31/2019 completed the survey. Lung (27%), thyroid (18%), salivary gland (14%), and colorectal (12%) were the most commonly reported tumor types. A majority (68%) tested NTRK status prior to 1L initiation; testing after disease progression on 1L (36%), 2L (25%), and 3L (21%) was also noted. Most oncologists (96%) reported no difficulty interpreting NTRK reports. Nearly all (96%) indicated using next-generation sequencing (NGS) for determining NTRK status. The majority (57%) indicated that age, tumor type, and performance status did not impact NTRK testing decisions. Less than half (46%) include TRKi therapy following NTRK+ determination. NTRK testing guidelines were commonly reviewed by physicians (89%). CONCLUSION AND RELEVANCE: Among patients with advanced/metastatic TRK fusion cancer, medical oncologists reported testing for NTRK fusions at diagnosis or prior to 1L. Future research should elucidate why fewer than half of oncologists surveyed (46%) would not use TRKis after NTRK+ status confirmation, assess clinical practices among NTRK+ patients, and characterize treatment patterns and clinical outcomes in real-world settings.

Value-Based Analysis of Therapies in Refractory Metastatic Colorectal Cancer in US.

BACKGROUND: Recent phase 2 trials have provided data supporting regorafenib dose optimization (ReDO) and trifluridine/tipiracil (TAS-102) with bevacizumab (TAS-BEV) as treatment options in refractory metastatic colorectal cancer (mCRC). Historically, regorafenib standard dose (RSD) and TAS-102 have been utilized as third-line options in mCRC. Given the incorporation of ReDO and TAS-BEV as treatment options, we sought to evaluate relative cost-effectiveness of ReDO vs. RSD, TAS-102, and TAS-BEV for mCRC from a payer perspective. METHODS: A Markov model was constructed to estimate total costs and quality-adjusted life-years (QALYs) for ReDO, RSD, TAS-102, and TAS-BEV. Clinical parameters were obtained from phase 2 and 3 trials for comparators. Health state utility values were from the RSD phase 3 clinical trial. Incremental cost-effectiveness ratios (ICERs) were utilized to compare treatments. Model robustness was checked with one-way and probabilistic sensitivity analyses. RESULTS: In the base case, ReDO was dominant over TAS-BEV (ie provided a higher QALY at a lower cost). ReDO produced an ICER of $104,308 per QALY relative to RSD and $37,966 relative to TAS-102. In one-way sensitivity analyses, monthly drug cost of TAS-BEV was the most influential parameter determining relative cost-effectiveness between TAS-BEV and ReDO. When TAS-102 and RSD were independently compared to ReDO, the most influential parameters were related to duration of OS and PFS and costs of managing AEs. CONCLUSIONS: The optimum dosing strategy for regorafenib has improved its benefit-to-toxicity ratio and relative cost-effectiveness compared to RSD, TAS-102, and TAS-BEV.

Treatment Patterns of Real-World Patients with TRK Fusion Cancer Treated by US Community Oncologists.

BACKGROUND: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are present across various tumor types with an estimated overall prevalence of less than 1%. Tropomyosin receptor kinase inhibitors (TRKis) block the constitutively activated tyrosine receptor kinase (TRK) fusion protein produced in cancers with NTRK gene fusions (NTRK+) from downstream signaling. Many treatment guidelines now include TRKis as first-line (1L) or subsequent treatment options for TRK fusion cancer. OBJECTIVE: This study aimed to assess treatment patterns subsequent to a finding of NTRK+ status among patients with TRK fusion cancer. PATIENTS AND METHODS: This was a one-time, retrospective, multi-site patient chart abstraction by oncology practices in the USA from June to September 2020. US medical oncologists from the Oncology Provider Extended Network (OPEN) who had treated patients with NTRK+ advanced/metastatic solid tumors abstracted information into electronic case report forms (eCRFs) for adult patients with advanced/metastatic solid tumors and a NTRK+ tumor test result with a known fusion partner. Data abstracted into eCRFs by oncologists included demographic, clinical, and treatment characteristics of patients with advanced/metastatic TRK fusion solid tumors. Responses were summarized using descriptive statistics. Median treatment durations across the lines of therapy were estimated by Kaplan-Meier time to discontinuation. RESULTS: A total of 19 medical oncologists abstracted data from 110 patient charts. Median patient age at advanced/metastatic diagnosis was 62 years. The majority of patients were male (58.2%) and White (79.1%). Solid tumor types reported in at least 10% of the study cohort were lung (24.5%), cholangiocarcinoma (13.6%), pancreatic (10.9%), and colorectal (10.0%). Results for patients with hepatobiliary cancers (i.e., cholangiocarcinoma, pancreatic cancer, hepatocellular carcinoma) and colorectal cancer, and appendiceal cancer are also included. Median duration of 1L TRKi therapy was 16.8 months across all solid tumor types, whereas median duration of 1L was 5.6 months among patients receiving non-TRKi therapies (p = 0.017). Among the solid tumor types represented by at least 10% of the study population, median duration of 1L TRKi therapy was only reached in patients with pancreatic cancer (3.3 months). Median duration of TRKi in the second-line (2L) setting was 7.9 months overall, relative to 5.3 months among patients receiving non-TRKi therapies (p = 0.003). Across lung, cholangiocarcinoma, pancreatic, and colorectal cancers, the median durations of 2L TRKi therapy were 14.1, 6.0, 6.1, and 4.1 months, respectively. CONCLUSION AND RELEVANCE: Among patients with advanced/metastatic TRK fusion solid tumors, medical oncologists reported that approximately two-thirds initiated a TRKi during the study period. Treatment with a TRKi was longer in duration compared to non-TRKi treatment in 1L and 2L therapy. Additional research is needed to gain insight into the association between early TRKi therapy initiation and clinical outcomes in the real-world setting.

Omalizumab Treatment Patterns Among Patients with Asthma in the US Medicare Population.

BACKGROUND: Asthma in older adults is associated with high rates of morbidity and mortality; similarly, asthma can be severe enough among younger adults to warrant disability benefits. Reasons for poor outcomes in both groups of patients may include discontinuation and lack of adherence to controller therapies. OBJECTIVE: To examine characteristics and treatment patterns of US Medicare patients initiating omalizumab for asthma, and factors associated with its discontinuation and adherence. METHODS: A retrospective claims database analysis of Medicare beneficiaries with asthma initiating omalizumab treatment was carried out. The primary outcomes were omalizumab discontinuation (gap in use ≥90 days) and adherence (proportion of days covered ≥0.8) over a 12-month follow-up. Multivariable regressions were used to examine factors associated with omalizumab discontinuation and adherence. RESULTS: Of the 3058 Medicare patients initiating omalizumab for asthma (mean age, 62.7 years), 36.9% discontinued omalizumab and 60.6% were adherent. Discontinuation rates were 32.7% and 42.8%, and adherence rates were 65.4% and 53.9%, for disabled and older Medicare patients, respectively. Patients aged 65 to 69 years and 70 to 74 years had significantly lower odds of discontinuation (odds ratios [95% CI], 0.66 [0.46-0.93] and 0.62 [0.43-0.89], respectively) and higher odds of adherence than did patients aged 80 years or older. Compared with patients receiving low-income subsidy, patients not receiving low-income subsidy had lower odds of discontinuation (0.66 [0.52-0.83]) and higher odds of adherence (1.52 [1.20-1.93]). Greater numbers of preindex evaluation and management physician visits and comorbid rhinitis were associated with lower odds of discontinuation and higher odds of adherence. CONCLUSIONS: More than 60% of Medicare patients with asthma continued and were adherent to omalizumab over a 12-month follow-up. Patient age, low-income subsidy status, and the numbers of evaluation and management physician visits were among factors associated with treatment adherence and discontinuation.

Cost-effectiveness of omalizumab for the treatment of moderate-to-severe uncontrolled allergic asthma in the United States.

Objective: Uncontrolled asthma is associated with considerable clinical burden and costs to payers and patients. US economic models evaluating biologics using data from clinical trials demonstrate high incremental cost-effectiveness ratios (ICERs), but the cost-effectiveness based on real-world treatment patterns is unknown. This analysis used real-world evidence to assess the cost-effectiveness of adding omalizumab to standard of care (SOC).Methods: A Markov model was applied to track patients' health states in 2-week cycles, comparing costs and treatment effects of SOC alone versus SOC + omalizumab over a lifetime (US payer perspective). Outcomes included exacerbation events, life years, quality-adjusted life years (QALYs), total costs, and an ICER. Patient characteristics, exacerbations, patient-reported outcomes, and work productivity were derived from the real-world PROSPERO (Prospective Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab) study. Published literature informed mortality, exacerbation-related disutility, and unit costs. Sensitivity analyses assessed model robustness.Results: Over a lifetime horizon, omalizumab was associated with an increase of 2.0 QALYs at a cost of $US 148,319 in patients with uncontrolled asthma (ICER of $75,319/QALY gained) and a reduction in exacerbations of 6.0 events/patient. Accounting for responder status improved the ICER ($70,505/QALY); incorporating indirect costs further reduced the ICER. One-way and multivariate sensitivity analyses confirmed that the base case outcome was robust to variation in inputs.Conclusions: Based on real-world outcomes, omalizumab may be cost-effective for uncontrolled asthma from the US payer perspective. Including broader evidence on treatment discontinuation, caregiver burden, and oral corticosteroid reduction from real-world studies may better reflect the effects and value of omalizumab for all healthcare stakeholders.

Contemporary Treatment Patterns and Clinical Outcomes of Comorbid Diabetes Mellitus and HFrEF: The CHAMP-HF Registry.

OBJECTIVES: The purpose of this study was to characterize the clinical profile, treatment patterns, and clinical outcomes of patients with comorbid diabetes mellitus (DM) and heart failure with reduced ejection fraction (HFrEF) in a contemporary, real-world U.S. outpatient registry in the context of evolving treatment strategies. BACKGROUND: Specific antihyperglycemic classes have differential risks and benefits with respect to HF. Limited data are available evaluating contemporary treatment patterns and outcomes of patients with comorbid DM and HFrEF. METHODS: Among 4,970 patients with chronic HFrEF (≤40%) across 152 U.S. sites in the CHAMP-HF prospective, observational registry (2015 to 2017), we examined therapies and clinical outcomes by DM status. RESULTS: Median age was 68 (58 to 75) years of age; 29% were women; 73.5% were white; and 64% had coronary artery disease. Overall, 42% (n = 2,085) had comorbid DM with a median hemoglobin A1c (HbA1c) level of 7.2% (interquartile range [IQR]: 6.4% to 8.3%). One-fourth of DM patients (24%) were not treated with an antihyperglycemic therapy. Most patients with DM were taking 1 (46%) or 2 (23%) antihyperglycemic therapies: metformin (40%); insulin (33%); sulfonylureas (24%); dipeptidyl peptidase-4 inhibitors (10%); glucagon-like peptide (GLP)-1 receptor agonists (4%); sodium-glucose cotransporter (SGLT)-2 inhibitors (2%); and thiazolidinediones (2%). Among patients with DM, 62%, 16%, 80%, and 33.5% were receiving any angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitor (ARNI), ß-blockers, or mineralocorticoid receptor antagonists (MRAs) at baseline, respectively. Among patients without DM, corresponding baseline rates were 65%, 15%, 80%, and 37%, respectively. Patients with or without DM were infrequently treated with guideline-directed HFrEF therapies at target doses (≤27% across classes). During median 15-month follow-up, patients with DM experienced higher rates of all-cause mortality or HF hospitalization (30% vs. 23%, respectively), independent of 11 pre-specified covariates (adjusted hazard ratio: 1.35 (95% confidence interval: 1.21 to 1.52); p < 0.001). CONCLUSIONS: Despite higher risk-adjusted clinical event rates in patients with comorbid HFrEF and DM, guideline-directed medical therapies for both disease states are incomplete and represent an important target for quality improvement through multidisciplinary care pathways.

Patient Perceptions and Familiarity With Medical Therapy for Heart Failure.

Importance: There are major gaps in use of guideline-directed medical therapy (GDMT) for patients with heart failure (HF). Patient-reported data outlining patient goals and preferences associated with GDMT are not available. Objective: To survey patients with chronic HF to better understand their experiences and perceptions of living with HF, including their familiarity and concerns with important GDMT therapies. Design, Setting, and Participants: Study participants were recruited from the GfK KnowledgePanel, a probability-sampled online panel representative of the US adult population. English-speaking adults who met the following criteria were eligible if they were (1) previously told by a physician that they had HF; (2) currently taking medications for HF; and (3) had no history of left ventricular assist device or cardiac transplant. Data were collected between October and November 2018. Analysis began in December 2018. Main Outcomes and Measures: The survey included 4 primary domains: (1) relative importance of disease-related goals, (2) challenges associated with living with HF, (3) decision-making process associated with HF medication use, and (4) awareness and concerns about available HF medications. Results: Of 30 707 KnowledgePanel members who received the initial survey, 15 091 (49.1%) completed the screening questions, 440 were eligible and began the survey, and 429 completed the survey. The median (interquartile range) age was 68 (60-75) years and most were white (320 [74.6%]), male (304 [70.9%]), and had at least a high school education (409 [95.3%]). Most survey responders reported familiarity with ß-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics. Overall, 107 (24.9%) reported familiarity with angiotensin receptor-neprilysin inhibitors or mineralocorticoid receptor antagonists. Overall, 136 patients (42.5%) reported have safety concerns regarding angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and 133 (38.5%) regarding ß-blockers, 35 (37.9%) regarding mineralocorticoid receptor antagonists, 38 (36.5%) regarding angiotensin receptor-neprilysin inhibitors, and 123 (37.2%) regarding diuretics. Between 27.7% (n = 26) and 38.5% (n = 136) reported concerns regarding the effectiveness of ß-blockers, angiotensin receptor-neprilysin inhibitors, mineralocorticoid receptor antagonists, or diuretics, while 41% (n = 132) were concerned with the effectiveness of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Conclusions and Relevance: In this survey study, many patients were not familiar with GDMT for HF, with familiarity lowest for angiotensin receptor-neprilysin inhibitors and mineralocorticoid receptor antagonists. Among patients not familiar with these therapies, significant proportions questioned their effectiveness and/or safety. Enhanced patient education and shared decision-making support may be effective strategies to improve the uptake of GDMT for HF in US clinical practice.