Dupilumab improves health-related quality of life in patients with chronic rhinosinusitis with nasal polyposis.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) negatively affects health-related quality of life (HRQoL). In a previously reported randomized clinical trial (NCT01920893), addition of dupilumab to mometasone furoate in patients with CRSwNP refractory to intranasal corticosteroids (INCS) significantly improved endoscopic, radiographic, and clinical endpoints and patient-reported outcomes. The objective of this analysis was to examine the impact of dupilumab treatment on HRQoL and productivity using secondary outcome data from this trial. METHODS: Following a 4-week mometasone furoate nasal spray run-in, patients were randomized to commence subcutaneous dupilumab (600 mg loading dose, then 300 mg once weekly for 15 weeks [n = 30], or matched placebo [n = 30]). Outcomes included scores on the CRS disease severity visual analog scale (VAS), 22-item Sino-Nasal Outcome Test (SNOT-22), 5-dimension EuroQoL (EQ-5D) general health status VAS, and 36-item Short-Form Health Survey (SF-36) for HRQoL and nasal polyp-related healthcare resource use questionnaires. RESULTS: Following 16 weeks of treatment, the proportion of patients with moderate-to-severe CRSwNP (VAS > 3-10) decreased from 86.2% to 21.4% with dupilumab and 88.0% to 84.2% with placebo. Dupilumab (vs placebo) resulted in significantly greater improvement in HRQoL, based on SNOT-22, SF-36, and EQ-5D VAS scores. The dupilumab group had a significantly lower adjusted annualized mean number of sick leave days (0.09, vs 4.18 with placebo, P = .015) and significantly greater improvement (vs placebo) in the SNOT-22 item "reduced productivity." CONCLUSIONS: In adults with CRSwNP refractory to treatment with INCS alone, the addition of dupilumab reduced disease severity, significantly improved HRQoL, and improved productivity.

Dupilumab reduces opacification across all sinuses and related symptoms in patients with CRSwNP.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with substantial sinus opacification. In a phase 2a study (NCT01920893), dupilumab, a fully human anti-IL-4Rα monoclonal antibody, improved outcomes in CRSwNP refractory to intranasal corticosteroids. We evaluated dupilumab’s effect on sinus opacification in relation to effects on nasal polyp burden, symptoms, and health-related quality of life (HRQoL) in patients with CRSwNP. METHODOLOGY: 16-week randomized, double-blind, placebo-controlled, parallel-group study in 60 adults with CRSwNP. Patients received weekly subcutaneous dupilumab 300-mg or placebo and daily mometasone furoate nasal spray. Sinus opacification was assessed using standard and Zinreich-modified Lundâ€"Mackay (zLMK) scoring. Correlation was assessed between zLMK score and CRSwNP endpoints, including nasal polyp score (NPS), SNOT-22, daily symptom scores, and UPSIT smell-test score. RESULTS: Baseline characteristics were similar across treatment groups. Mean plus/minus SD baseline LMK scores of 18.7 plus/minus 5.5 (placebo) and 18.6 plus/minus 5.0 (dupilumab) indicated severe disease with extensive opacification involving all sinuses. Baseline LMK and LMK scores correlated with NPS severity and loss of sense of smell (daily symptoms; SNOT-22 smell/taste; loss of sense of smell [UPSIT]). At Week 16, dupilumab-treated patients had significantly improved sinus opacification measured by LMK in all individual sinuses vs placebo. Dupilumab also showed similar efficacy with zLMK, with only small differences from LMK, and correlated with SNOT22 smell/taste. The most common adverse events were nasopharyngitis, injection-site reactions, and headache. CONCLUSIONS: In patients with CRSwNP, baseline LMK showed extensive sinus opacification and correlated with symptoms, HRQoL, and hyposmia. Dupilumab treatment reduces opacification across all sinuses and related symptoms in patients with CRSwNP.

TELEPRO: Patient-Reported Carcinoid Syndrome Symptom Improvement Following Initiation of Telotristat Ethyl in the Real World.

BACKGROUND: When carcinoid syndrome (CS) diarrhea (CSD) is inadequately controlled with long-acting somatostatin analogs (SSAs), clinical practice guidelines recommend addition of the tryptophan hydroxylase inhibitor telotristat ethyl (TE). In a 12-week multinational, randomized controlled trial, TE added to SSA reduced peripheral serotonin and the frequency of CSD. We evaluated real-world effectiveness of TE using patient-reported data from a nurse support program over 3 months. MATERIALS AND METHODS: This study used a deidentified data set of patients initiating TE who opted into a nurse support program between March and November 2017 and reported CS symptom burden at baseline and at least one follow-up time point at months 1, 2, and 3. Patients reported demographic and medical history information as well as frequency of bowel movements (BMs) and flushing episodes, severity of nausea, urgency and abdominal pain (0 "no/not at all" to 100 "worst imaginable/very urgent"), and stool form (1 "very hard" to 10 "watery"). Mean changes from baseline in CS symptom burden were reported using paired-sample t tests and Wilcoxon signed-rank tests. RESULTS: Most patients initiating TE enrolled in the nurse program (791/898, 88%), of whom 369 (47%) were included in the analysis. Patients treated with TE reported significant reductions in CSD and other CS symptoms (all p < .001). At least half of patients treated with TE experienced ≥30% improvement from baseline in BM frequency and an average reduction of at least two BMs per day within 3 months. CONCLUSION: Patients taking SSA therapy showed substantial burden of disease before initiating TE and significant improvements with the addition of TE treatment in this real-world effectiveness study. IMPLICATIONS FOR PRACTICE: Patients with carcinoid syndrome diarrhea uncontrolled by high doses of long-acting somatostatin analogs may be candidates for additional therapy with the tryptophan hydroxylase inhibitor telotristat ethyl. Understanding the real-world prevalence of uncontrolled symptoms and the effectiveness of telotristat ethyl in clinical practice may further support clinical and policy decisions for these patients. This study investigated self-reported carcinoid syndrome symptom burden and improvements among patients initiating telotristat ethyl and participating in a voluntary nurse support program. Disease burden and off-label somatostatin analog treatment before initiating telotristat ethyl were high, and symptoms improved markedly over 1, 2, and 3 months of treatment.

Dupilumab improves symptoms, quality of life, and productivity in uncontrolled persistent asthma.

BACKGROUND: In a pivotal, phase 2b study (NCT01854047) in patients with uncontrolled persistent asthma, despite using medium-to-high-dose inhaled corticosteroids plus long-acting ß2 agonists, dupilumab improved lung function, reduced severe exacerbations, and showed an acceptable safety profile. OBJECTIVE: To assess the impact of dupilumab on asthma control, symptoms, quality of life (QoL), and productivity. METHODS: Data are shown for the intention-to-treat population receiving dupilumab 200/300 mg every 2 weeks (doses being assessed in phase 3; NCT02414854), or placebo. Predefined analyses of total scores were conducted at week 24 for the 5-item Asthma Control Questionnaire (ACQ-5), patient-reported morning/evening (AM/PM) asthma symptoms, Asthma Quality of Life Questionnaire (AQLQ), and asthma-related productivity loss. Responder rate analyses for these measures, subgroup analyses by baseline characteristics, and asthma-related productivity loss analyses were conducted post hoc. RESULTS: Data from 465 patients were analyzed (158 placebo; 307 dupilumab). Both dupilumab doses significantly improved scores through week 24 (all outcomes, overall population). The proportion of patients meeting or exceeding the minimal clinically important difference for the overall population were significantly greater vs placebo (P < .05) for ACQ-5 (range, 72.6%-76.7% vs 61.4%), for AM/PM asthma symptoms score (48.7%-54.1% vs 34.2% and 52.7%-53.5% vs 34.2%, respectively) and for AQLQ (64.0%-65.0% vs 51.3%). The effect of dupilumab was consistent across most subgroups. Productivity loss was significantly higher in placebo- vs dupilumab-treated patients (P < .0001). CONCLUSION: Dupilumab produced significant, clinically meaningful improvements in asthma control, symptoms, QoL, and productivity. REGISTRATION: ClinicalTrials.gov Identifier: NCT01854047.

Serotonin levels and 1-year mortality in patients with neuroendocrine tumors: a systematic review and meta-analysis.

Aim: Elevated serotonin in patients with neuroendocrine tumors (NETs) may impact heart failure incidence but a quantitative relationship has not been established. Materials & methods: Systematic review and meta-analysis of studies assessing 24-h urinary 5-hydroxyindoleacetic acid (u5-HIAA) and mortality in patients with NETs (2007-2017) with a primary outcome of 1-year mortality risk and 24-h u5-HIAA. Results: We identified 1715 records of which 12 studies including 755 patients (3442 person-years with 376 deaths) were eligible for meta-analysis. Mean u5-HIAA was 149.2 mg/24 h (standard deviation: 96.6) and mortality was 13.0%. The meta-regression equation showed an 11.8% (95% CI: 8.9-17.0%; I2  = 93.0%) increase in 1-year mortality for every ten-unit increase in u5-HIAA. Conclusion: Serotonin measured by its metabolite u5-HIAA is predictive of 1-year all-cause mortality in patients with NETs.

Efficacy and safety of dupilumab in perennial allergic rhinitis and comorbid asthma.

BACKGROUND: Dupilumab, an anti-IL-4 receptor α mAb, inhibits IL-4/IL-13 signaling, key drivers of type 2/TH2 immune diseases (eg, atopic/allergic disease). In a pivotal, phase 2b study (NCT01854047), dupilumab reduced severe exacerbations, improved lung function and quality of life, and was generally well tolerated in patients with uncontrolled persistent asthma despite using medium-to-high-dose inhaled corticosteroids plus long-acting ß2-agonists. OBJECTIVE: To examine dupilumab's effect on the 22-item Sino-Nasal Outcome Test (SNOT-22) total score and its allergic rhinitis (AR)-associated items in asthma patients with comorbid perennial allergic rhinitis (PAR). METHODS: A post hoc analysis reporting data from the phase 2b study for the 200 and 300 mg every 2 week (q2w) doses under investigation in phase 3 (NCT02414854) was carried out. PAR was defined at study entry as a specific response to typical perennial antigens (IgE ≥0.35 Ku/L). RESULTS: Overall, 241 (61%) patients had PAR. In asthma patients with PAR, dupilumab 300 mg q2w versus placebo significantly improved SNOT-22 total score (least squares mean difference, -5.98; 95% CI, -10.45 to -1.51; P = .009) and all 4 AR-associated symptoms evaluated (nasal blockage, -0.60; 95% CI, -0.96 to -0.25; runny nose, -0.67; 95% CI, -1.04 to -0.31; sneezing, -0.55; 95% CI, -0.89 to -0.21; postnasal discharge, -0.49; 95% CI, -0.83 to -0.16; all P < .01). Dupilumab 200 mg q2w demonstrated numerical, but not statistically significant, decreases in SNOT-22 total score (-1.82; 95% CI, -6.46 to 2.83; P = .443 vs placebo) and in each AR-associated symptom. In patients without PAR, no differences were observed for these measures versus placebo. CONCLUSIONS: Dupilumab 300 mg q2w significantly improved AR-associated nasal symptoms in patients with uncontrolled persistent asthma and comorbid PAR.

Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting ß2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial.

BACKGROUND: Dupilumab, a fully human anti-interleukin-4 receptor α monoclonal antibody, inhibits interleukin-4 and interleukin-13 signalling, key drivers of type-2-mediated inflammation. Adults with uncontrolled persistent asthma who are receiving medium-to-high-dose inhaled corticosteroids plus a long-acting ß2 agonist require additional treatment options as add-on therapy. We aimed to assess the efficacy and safety of dupilumab as add-on therapy in patients with uncontrolled persistent asthma on medium-to-high-dose inhaled corticosteroids plus a long-acting ß2 agonist, irrespective of baseline eosinophil count. METHODS: We did this randomised, double-blind, placebo-controlled, parallel-group, pivotal phase 2b clinical trial at 174 study sites across 16 countries or regions. Adults (aged ≥18 years) with an asthma diagnosis for 12 months or more based on the Global Initiative for Asthma 2009 Guidelines receiving treatment with medium-to-high-dose inhaled corticosteroids plus a long-acting ß2 agonist were eligible for participation. Patients were randomly assigned (1:1:1:1:1) to receive subcutaneous dupilumab 200 mg or 300 mg every 2 weeks or every 4 weeks, or placebo, over a 24-week period. The primary endpoint was change from baseline at week 12 in forced expiratory volume in 1 s (FEV1 in L) in patients with baseline blood eosinophil counts of at least 300 eosinophils per µL assessed in the intention-to-treat population. Safety outcomes were assessed in all patients that received at least one dose or part of a dose of study drug. This trial is registered at ClinicalTrials.gov, number NCT01854047, and with the EU Clinical Trials Register, EudraCT number 2013-000856-16. FINDINGS: 769 patients (158 in the placebo group and 611 in the dupilumab groups) received at least one dose of study drug. In the subgroup with at least 300 eosinophils per µL, the greatest increases (200 mg every 2 weeks, p=0·0008; 300 mg every 2 weeks, p=0·0063) in FEV1 compared with placebo were observed at week 12 with doses every 2 weeks in the 300 mg group (mean change 0·39 L [SE 0·05]; mean difference 0·21 [95% CI 0·06-0·36; p=0·0063]) and in the 200 mg group (mean change 0·43 L [SE 0·05]; mean difference 0·26 [0·11-0·40; p=0·0008]) compared with placebo (0·18 L [SE 0·05]). Similar significant increases were observed in the overall population and in the fewer than 300 eosinophils per µL subgroup (overall population: 200 mg every 2 weeks, p<0·0001; 300 mg every 2 weeks, p<0·0001; <300 eosinophils per µL: 200 mg every 2 weeks, p=0·0034; 300 mg every 2 weeks, p=0·0086), and were maintained to week 24. Likewise, dupilumab every 2 weeks produced the greatest reductions in annualised rates of exacerbation in the overall population (70-70·5%), the subgroup with at least 300 eosinophils per µL (71·2-80·7%), and the subgroup with fewer than 300 eosinophils per µL (59·9-67·6%). The most common adverse events with dupilumab compared with placebo were upper respiratory tract infections (33-41% vs 35%) and injection-site reactions (13-26% vs 13%). INTERPRETATION: Dupilumab increased lung function and reduced severe exacerbations in patients with uncontrolled persistent asthma irrespective of baseline eosinophil count and had a favourable safety profile, and hence in addition to inhaled corticosteroids plus long-acting ß2-agonist therapy could improve the lives of patients with uncontrolled persistent asthma compared with standard therapy alone. FUNDING: Sanofi-Genzyme and Regeneron Pharmaceuticals.

Healthcare burden of pulmonary hypertension owing to lung disease and/or hypoxia.

BACKGROUND: Group 3 pulmonary hypertension (PH) encompasses PH owing to lung diseases and/or hypoxia. Treatment patterns, healthcare resource use, and economic burden to US payers of Group 3 PH patients were assessed. METHODS: This retrospective observational study extracted data from July 1, 2010 to June 30, 2013 from two Truven Health Analytics MarketScan databases. Adult Group 3 PH patients were identified based on claims for PH (ICD-9-CM 416.0/416.8), a related lung disease, and an echocardiogram or right heart catheterization (RHC). The index date was the date of the first PH claim; data were collected for 12 months pre- and post-index. A difference-in-difference approach using generalized estimating equations was done to account for baseline differences. RESULTS: Group 3 PH patients (n = 2,236) were matched 1:1 to controls on lung disease. PH patients had higher all-cause resource utilization and annual healthcare costs ($44,732 vs. $7,051) than controls. Costs were driven by inpatient admissions (35.4% of total costs), prescriptions (33.0%), and outpatient care (26.5%). Respiratory-related costs accounted for 11.4% of post-index annual costs for PH patients. PH diagnosis was not confirmed in the majority of PH patients (<7% RHC use) but nevertheless, 22% of PH patients post-index had claims for drugs approved for the treatment of pulmonary arterial hypertension (PAH). CONCLUSIONS: Group 3 PH poses a significant clinical and economic burden. Given the low use of RHC and the prevalence of PAH-indicated prescriptions that are not currently approved for Group 3 PH, this study suggests some Group 3 PH patients may not be receiving guideline-recommended treatment.

Implications of early treatment among Medicaid patients with Alzheimer's disease.

OBJECTIVE: The objective of this study was to examine the effect of treatment timing on risk of institutionalization of Medicaid patients with Alzheimer's disease (AD) and to estimate the economic implications of earlier diagnosis and treatment initiation. METHODS: New Jersey Medicaid claims data (1997-2009) were used retrospectively to study the effect of treatment on time to institutionalization. Observed Medicaid payments were used to calculate savings from delayed institutionalization, adjusting for cost offsets resulting from concurrent changes in use of other medical services. RESULTS: Initiation of existing therapies at earliest symptomatic onset is predicted to delay institutionalization by 91 days, reducing Medicaid costs by $19,108/institutionalized patient. Incorporating an 18.5% cost offset from increased use of other medical services as well as drug costs associated with earlier treatment results in net savings of $12,687/patient. Projected annual Medicaid savings exceed $1 billion. CONCLUSION: Earlier treatment leads to a small delay in institutionalization among AD patients, resulting in significant costs savings to Medicaid.

Impact of Ruxolitinib Cream on Work Productivity and Activity Impairment and Associated Indirect Costs in Patients with Atopic Dermatitis: Pooled Results From Two Phase III Studies.

BACKGROUND: Atopic dermatitis is a chronic inflammatory skin disease that can negatively impact work productivity and daily activities. Ruxolitinib cream, a Janus kinase inhibitor, demonstrated efficacy and safety in patients with atopic dermatitis in two phase III studies (TRuE-AD1 and TRuE-AD2). OBJECTIVE: This post hoc analysis sought to describe the effects of ruxolitinib cream on work productivity and activity impairment from pooled data from the phase III studies, to estimate indirect costs due to atopic dermatitis, and to estimate the incremental cost savings with ruxolitinib cream versus vehicle cream. METHODS: Patients in both studies were ≥ 12 years old with atopic dermatitis for ≥ 2 years, an Investigator's Global Assessment score of 2 or 3, and a 3-20% affected body surface area at baseline. Patients were randomized 2:2:1 to receive ruxolitinib cream (0.75% or 1.5%) or vehicle cream for 8 weeks. Patient self-reported productivity in the efficacy-evaluable population was assessed at weeks 2, 4, and 8 using the Work Productivity and Activity Impairment Questionnaire-Specific Health Problem version 2.0. Statistical significance for the two doses versus vehicle was calculated using an analysis of covariance. Work Productivity and Activity Impairment overall work impairment scores were converted to a model of costs per employed patient due to lost productivity and incremental cost savings from ruxolitinib cream treatment using a human capital approach. RESULTS: Of 1249 patients enrolled (median age, 32 years; female sex, 61.7%), 1208 were included in the efficacy-evaluable population. Patients applying 0.75% or 1.5% ruxolitinib cream had significant changes in overall work impairment (- 17.9% [0.75% strength] and - 15.0% [1.5% strength] vs - 5.7% for vehicle; p < 0.0001 for both) and daily activity impairment (- 20.6% [0.75% strength] and - 21.5% [1.5% strength] vs - 10.6% for vehicle; p < 0.0001 for both). These corresponded to estimated lost productivity costs in 2021 US dollars of $1313 (0.75% strength) and $1242 (1.5% strength) versus $2008 (vehicle) over the 8-week trial period. Compared with a patient receiving vehicle, incremental annual indirect cost savings were estimated to be $5302 with 0.75% ruxolitinib cream and $4228 with 1.5% ruxolitinib cream. CONCLUSIONS: Ruxolitinib cream therapy is associated with improved work productivity and daily activity compared with vehicle and is estimated to reduce the indirect cost burden on the patient. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT03745638 (registered 19 November, 2018) and NCT03745651 (registered 19 November, 2018).

Antidepressant use in geriatric populations: the burden of side effects and interactions and their impact on adherence and costs.

OBJECTIVES: The study aimed to determine the prevalence of documented side effects and drug­drug interactions in older adults using antidepressants and their implications for adherence. DESIGN: Data were from the MarketScan Medicare Database,which comprises insurance claims from retirees with employer-sponsored Medicare supplemental insurance. Subjects were aged 65 years or older, new antidepressant users, and had a depression diagnosis between July 1, 2001, and December 31, 2006.Twelve commonly reported antidepressant side effects were identified in the month after drug initiation through International Classification of Diseases, Ninth Revision,Clinical Modification diagnoses. Potential drug- drug interactions involving an antidepressant and another drug were identified during the 1 year after antidepressant initiation using MicroMedex DRUG-REAX software. Multinomial logistic regression was used to determine the association of side effects and potential interactions with refills rates, switching, and discontinuation. RESULTS: The presence of a side effect was associated with a 4.7 percentage point increase in the probability of switching (from 16.5% to 21.7%) and a 3.7 percentage point increase in the discontinuation rate (from 22% to 25.7%). Among the 39,512 treatment-naive antidepressants users, 25.4% hadpotential contraindicated or major interactions, 36.1% had moderate interactions,and 38.5% had minor or no interactions. The presence of potential contraindicated or potential major interactions increased the probability of switching by 19.5 percentage points and had a minimal effect on discontinuation. CONCLUSION: Although antidepressant medications have been demonstrated to be effective in treatment of geriatric depression, this study highlights the complexity of antidepressant prescribing in this population and the need for clinicians to be aware of potential drug- drug interactions and side effects.

Changes in Carcinoid Syndrome Symptoms Among Patients Receiving Telotristat Ethyl in US Clinical Practice: Findings from the TELEPRO-II Real-World Study.

BACKGROUND: Inadequately controlled symptoms incur a substantial burden on patients with neuroendocrine tumors and carcinoid syndrome (CS). The effectiveness of telotristat ethyl (TE) with a somatostatin analog for uncontrolled CS diarrhea has been demonstrated in clinical trials and observational studies. TELEPRO-II was a prospective observational study evaluating TE's effectiveness in clinical practice over the first 3 months of treatment. METHODS: Patients initiating TE in 2018 participated in an optional nurse support program reporting CS symptoms during interviews at baseline and 1, 2, and 3 months after TE initiation. Eligible patients received TE for ≥3 months and reported symptom burden at baseline and ≥1 follow-up visit within the first 3 months. Daily bowel movement (BM) frequency and flushing episodes were reported as events/episodes per day. Stool consistency, nausea severity, urgency severity, and abdominal pain were reported on a severity scale (1-10). Symptom changes were evaluated using paired-sample t-tests and Wilcoxon signed-rank tests. Analysis of symptoms based on achievement of <30% or ≥30% reduction in daily BM frequency was conducted using a cumulative distribution function. RESULTS: A total of 684/1603 (43%) patients were eligible for analysis. At baseline, patients reported a mean of 6.3 BM/day, nausea severity of 8.4/10 and stool urgency of 8.2/10. Significant improvements in all CS symptoms were observed after 3 months of TE. Mean daily BMs were reduced 64% after 3 months of TE (mean reduction [SD], -3.99 [3.8]; P<0.0001). Most patients (74%, n=503) reported ≥30% reduction in daily BM frequency; these patients also reported improvements in other symptoms (76-87%). Patients with <30% reduction in daily BMs also reported improvements in nausea severity (62%, n=24), daily flushing episodes (66%, n=98), abdominal pain (50%, n=60), urgency severity (38%, n=64), and stool consistency (24%, n=44). CONCLUSION: Patients treated with TE in a real-world setting experienced significant, clinically meaningful improvements in CS symptoms.

Inadequate Disease Control, Treatment Dissatisfaction, and Quality-of-Life Impairments Among US Patients Receiving Topical Therapy for Atopic Dermatitis.

INTRODUCTION: Patients with atopic dermatitis (AD) experience burdensome symptoms and impaired quality of life (QoL). The objective of this study was to investigate the effects of topical AD therapies on disease control, physician and patient treatment satisfaction, and QoL in a real-world setting. METHODS: This was a retrospective, point-in-time study of physician-completed medical records and patient surveys drawn from two Adelphi AD Disease Specific Programmes™ (1. adults ≥ 18 years old; 2. pediatrics ≤ 17 years old) in the USA. Eligible physicians completed patient record forms and provided disease control assessments. Physicians and matched patients were surveyed regarding their satisfaction with current treatment. Patient-reported outcomes included the Dermatology Life Quality Index (DLQI), Children's DLQI (CDLQI), Patient-Oriented Eczema Measure (POEM), and the Work Productivity and Activity Impairment (WPAI) questionnaire. RESULTS: A total of 394 adult (topicals only, n = 284; topical plus systemic, n = 110) and 144 adolescent (aged 12-17 years; topicals only, n = 114; topical plus systemic, n = 30) patients who had received their current treatment for at least 1 month were included. Overall, 24.5% of patients had physician-reported uncontrolled disease (adults, 22.8%; adolescents, 29.2%). Rates of physician- and patient-reported dissatisfaction with current treatment were 32.0% (adults, 28.2%; adolescents, 42.4%) and 24.8% (adults, 24.0%; adolescents, 26.8%), respectively, and were higher for patients with uncontrolled versus controlled disease. Poorer disease control and higher rates of treatment dissatisfaction were generally reported among patients receiving topical plus systemic therapy versus topicals alone. Patients with uncontrolled versus controlled disease reported more impairment in the DLQI, CDLQI, POEM, and WPAI (P < 0.05 for all), with generally greater impairments observed among patients on topical plus systemic therapy versus topicals alone. CONCLUSION: Patients receiving topical AD therapies experienced uncontrolled disease and reported decreased overall functioning and lower QoL. An unmet need for topical AD treatments that improve disease control and patient outcomes exists.

Atopic dermatitis (or eczema) is a common skin condition that causes dry, cracked, and itchy skin. Patients are frequently prescribed topical therapy, such as ointments and creams, to apply directly to the affected skin. Additionally, patients may be prescribed systemic therapies, which are oral or injectable medications that work throughout the entire body. This study included 394 adults and 144 adolescents (aged 12­17 years) with atopic dermatitis. All patients in the study were receiving topical therapy, and some received both topical and systemic therapy. The goal of the study was to evaluate how satisfied patients and their doctors were with current treatment and to learn how patients in the study felt about their quality of life. Patients and their doctors completed surveys that asked about feelings, symptoms, and whether their condition affects their work. The study results showed that patients had high levels of dissatisfaction with their treatment. Doctors reported that between one-fifth and one-quarter of adult patients and up to one-half of adolescent patients had uncontrolled disease (defined as changeable or worsening). Patients with uncontrolled disease reported higher dissatisfaction with their therapy and a negative outlook on their quality of life versus those with controlled disease (defined as stable or improving by their doctors). In summary, doctors and their patients currently using topical medications to treat atopic dermatitis reported that treatments were not working well enough and that uncontrolled disease was negatively affecting patients' quality of life and work, indicating that additional treatment options are needed.

Improvement in Patient-Reported Outcomes in Adults with Type 1 Diabetes Treated with Sotagliflozin plus Insulin Versus Insulin Alone.

Background: Diabetes-related distress is common among persons affected by diabetes and is associated with suboptimal glycemic control and complications, thus constituting a relevant patient-report outcome (PRO). Improving glycemic control may reduce diabetes distress and improve treatment satisfaction. This post hoc analysis evaluated PRO data for a pooled cohort of adults with type 1 diabetes (T1D) receiving sotagliflozin as adjunct to optimized insulin in the inTandem1 and inTandem2 studies. Methods: Clinically meaningful changes in the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) and the two-item Diabetes Distress Scale (DDS2) total and individual scores were examined in the pooled data from the first 24 weeks of the studies. Results: In the cohort of patients with a baseline DTSQs total score ≤32 (∼76% of entire cohort), nearly twice as many patients treated with sotagliflozin 200 (45.9%) or 400 mg (42.3%) experienced a >3-point improvement from baseline versus those treated with placebo (24%). Treatment with sotagliflozin led to statistically significant (P < 0.05) improvements across all DTSQs items. Approximately 42% of all patients were considered to have a high risk of diabetes distress (total DDS2 score ≥6) at baseline following insulin optimization. More patients shifted from high to low risk with sotagliflozin compared with placebo (∼40% vs. 23%; P ≤ 0.0002). The baseline-adjusted difference in DDS2 from placebo was significantly (P < 0.001) reduced by -0.5 and -0.6 for sotagliflozin 200 and 400 mg, respectively. Conclusions: Patients with T1D treated with sotagliflozin in addition to optimized insulin therapy reported meaningful improvements in treatment satisfaction and diabetes distress. NCT02384941 and NCT02421510.

Employer burden of mild, moderate, and severe major depressive disorder: mental health services utilization and costs, and work performance.

BACKGROUND: Treatment utilization/costs and work performance for persons with major depressive disorder (MDD) by severity of illness is not well documented. METHODS: Using National Comorbidity Survey-Replication (2001-2002) data, US workforce respondents (n=4,465) were classified by clinical severity (not clinically depressed, mild, moderate, severe) using a standard self-rating scale [Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR)]. Outcomes included 12-month prevalence of medical services/medications use/costs and workplace performance. Treatment costs (employer's perspective) were estimated by weighing utilization measures by unit costs obtained for similar services used by MDD patients in claims data. Descriptive analysis across three severity groups generated chi(2) results. RESULTS: Using a sample of 539 US workforce respondents with MDD, 13.8% were classified mild, 38.5% moderate, and 47.7% severe cases. Mental health services usage, including antidepressants, increased significantly with severity, with average treatment costs substantially higher for severe than for mild cases both regarding mental health services ($697 vs. $388, chi(2)=4.4, P=.019) and antidepressants ($256 vs. $88, chi(2)=9.0, P=.001). Prevalence rates of unemployment/disability increased significantly (chi(2)=11.7, P=.003) with MDD severity (15.7, 23.3, and 31.3% for mild, moderate, and severe cases). Severely and moderately depressed workers missed more work than nondepressed workers; the monthly salary-equivalent lost performance of $199 (severely depressed) and $188 (moderately depressed) was significantly higher than for nondepressed workers (chi(2)=10.3, P<.001). Projected to the US workforce, monthly depression-related worker productivity losses had human capital costs of nearly $2 billion. CONCLUSIONS: MDD severity is significantly associated with increased treatment usage/costs, treatment adequacy, unemployment, and disability and with reduced work performance.

Clinical Benefits of Telotristat Ethyl in Patients With Neuroendocrine Tumors and Low Bowel Movement Frequency: An Observational Patient-Reported Outcomes Study.

OBJECTIVES: We evaluated carcinoid syndrome (CS) symptoms and the real-world effectiveness of telotristat ethyl (TE) among patients with ≤3 bowel movements (BM) per day. METHODS: Patients with CS initiating TE between March and November 2017 could participate in a nurse support program collecting demographic and CS symptom data before TE initiation (baseline) and during ≥1 monthly follow-up within 3 months. Symptoms for patients averaging ≤3 BM/d at baseline were evaluated using pre/post-Student t tests. RESULTS: Sixty-eight patients reported ≤3 BM/d at baseline. Symptom burden was high and similar to participants with higher daily BM frequency. After 3 months of TE, most patients reported stable or improved symptoms with significant improvements in urgency (88%; mean [SD], -13.2 [32.2]), stool consistency (88%; -1.3 [2.0]), BMs per day (81%; -0.2 [1.2]), abdominal pain (86%; -13.7 [25.8]), nausea (85%; -30.9 [35.7]), and daily flushing episodes (83%; -1.7 [4.4]; all except BMs per day, P < 0.05). CONCLUSIONS: This analysis illustrates high CS symptom burden among patients with relatively low daily BM frequency. After initiating TE, patients reported significant improvements in urgency, stool consistency, abdominal pain, nausea, and flushing episodes. Clinicians and population health managers should consider CS symptom burden beyond daily BM frequency when evaluating treatment selection.

Estimation of Annual Health Care Costs for Adults with Type 1 Diabetes in the United States.

BACKGROUND: Diabetes health care resource utilization (HCRU) studies tend to focus on patients with type 2 diabetes (T2D) or pool patients with T2D and type 1 diabetes (T1D). There is a paucity of recent data on the cost of treating patients with T1D in the United States. OBJECTIVES: To (a) estimate the per-patient per-year (PPPY) HCRU and costs, from a payer perspective, associated with treating U.S. adults with T1D and (b) compare these with the HCRU and costs for patients with T2D. METHODS: This retrospective cohort study used claims data from the Optum Clinformatics database between January 2015 and December 2017. Adults (aged ≥ 18 years) with a diagnosis of T1D were propensity score-matched to adults with T2D. Overall and nondiabetes-related HCRU and costs were assessed for T1D and T2D and compared between the 2 groups. RESULTS: Propensity scores were used to match 10,103 patient pairs from T1D and T2D cohorts (mean ages 54.4 and 56.9 years, respectively). In the T1D cohort, inpatient, emergency department (ED), outpatient, and prescription claims occurred in 14.0%, 17.3%, 85.5%, and 100% of patients, respectively, resulting in a mean total cost of U.S. $18,817 PPPY (diabetes-related = $11,002; nondiabetes-related = $7,816). The T1D cohort had significantly higher mean total costs than the T2D cohort ($18,817 vs. $14,148 PPPY; P < 0.001). When extrapolating these findings to a commercial health plan with 1 million covered lives, the estimated total direct medical costs of T1D would be $103.4 million. CONCLUSIONS: This study showed that the total annual cost of managing an adult with T1D is significantly higher than that of an adult with T2D. Nondiabetes costs accounted for 40% of the total per-patient cost, similar to patients with T2D, confirming that as patients with T1D live longer lives, they may also be at greater risk for cardiometabolic complications. DISCLOSURES: This study was funded by Sanofi U.S. and Lexicon Pharmaceuticals as part of a business partnership in a diabetes program at the time this study was conducted. Joish and Davies are employees and stockholders of Lexicon Pharmaceuticals. Zhou, Preblick, and Paranjape are employees and stockholders of Sanofi. Lin was a postdoctoral fellow at Sanofi through Rutgers University during this project. Deshpande provided consulting services through Communication Symmetry. Verma is an employee of Evidera, which was contracted by Sanofi for work on this study. Pettus is a consultant for Diasome, Insulet, Lexicon, Lilly, Mannkind, Novo Nordisk, Sanofi, and Senseonics.

Burden of Cardiovascular Disease in Adult Patients with Type 1 Diabetes in the US.

BACKGROUND AND OBJECTIVES: The burden imposed by cardiovascular disease (CVD) on patients with type 1 diabetes (T1D) in the US has not been thoroughly addressed. In a retrospective observational analysis of the Optum® Clinformatics™ Data Mart database, the prevalence of CVD and cardiovascular risk factors (CVRF) as well as health economic outcomes were evaluated in adults with T1D. METHODS: Patients with at least one T1D medical claim between January 1, 2016, and December 31, 2016, were divided into cohorts based on the presence of CVD and/or CVRF. Descriptive and multivariate analyses enabled comparisons of healthcare resource utilization and costs between the cohorts. RESULTS: The analysis included 12,687 patients: CVD, 2871; CVRF, 5371; and no CVD/CVRF, 4445. The period prevalence of CVD and CVRF in the combined baseline and follow-up periods was 27% and 44%, respectively. Fewer patients in the no-CVD/CVRF cohort had a claim of a diabetes-related inpatient admission compared with the CVD cohort (8% vs. 26%, respectively; P < 0.001, standardized mean difference [SMD] > 0.1). Likewise, fewer patients with no CVD/CVRF visited the emergency department vs. those with CVRF or CVD (diabetes-related: 4% vs. 7% and 18%, respectively; P < 0.001, SMD > 0.1). Higher overall costs were observed for the CVD and CVRF vs. the no-CVD/CVRF cohort ($30,241 and $16,220, respectively, vs. $11,761; P < 0.05 and SMD ≥ 0.1 for both). CONCLUSIONS: Cardiovascular comorbidities are common among US adults with T1D. Considering their significant economic burden, optimal management is of the utmost importance to improve patient outcomes and reduce healthcare costs.

Work productivity burden and indirect costs associated with carcinoid syndrome diarrhea.

Objectives: We estimated the indirect costs of work productivity burden from carcinoid syndrome diarrhea (CSD) among employed, insured adults in the United States. Methods: Retrospective cohort study of patients ≥18 years old with CS who did and did not have CSD (2014-2016). Eligible patients had continuous health plan enrollment for ≥12 months prior to their first CS claim and for ≥30 days after. Univariate analyses of clinical and work productivity outcomes and indirect costs were conducted. Multivariate analyses examined associations of CSD with work productivity measures, controlling for baseline characteristics. Results: A total of 1,880 patients with CS were eligible, including 577 with CSD and 1,303 with CS only. Baseline characteristics were generally similar. Patients with CSD missed half of eligible workdays (median 56%, 146/260); those with CS-only missed one-third (38%, 100/260). Work productivity was lower and the associated costs were higher in the presence of CSD. Patients with CSD had more absenteeism, short-term disability, and lost workdays which translated into incremental mean costs of $16,679 greater than those with CS only. Conclusion: Indirect costs related to work productivity losses among adults with CSD are significant, which further add to the burden of CSD to society.

Survival and Clinical Outcomes with Telotristat Ethyl in Patients with Carcinoid Syndrome.

PURPOSE: The TELEACE study showed reductions in tumor size in patients with neuroendocrine tumors, receiving telotristat ethyl in US clinical practice. Here, we report progression-free survival, time to tumor progression, changes in carcinoid syndrome symptoms, and indictors of overall health. PATIENTS AND METHODS: This was a retrospective, single arm, pre-post medical chart review of patients with locally advanced or metastatic neuroendocrine tumors and documented carcinoid syndrome receiving telotristat ethyl for at least 6 months. Patients with poorly differentiated tumors, mixed tumor types or conflicting clinical trial enrollment were excluded. Descriptive statistics, Kaplan-Meier and chi-square tests were used to evaluate PFS, tumor progression, changes in symptoms, body weight and ECOG performance status before and after telotristat ethyl initiation. Subgroup analyses were conducted in patients with the same pre- and post-telotristat ethyl background treatment. RESULTS: Anonymized data for 200 patients were provided by 114 physicians; patients received telotristat ethyl for a median of 9 months. Median time to tumor progression was 39.8 months (IQR, 18.7-39.8); most had no tumor progression at 6 (92%) and 12 months (87%). Median progression-free survival was 23.7 months (17.8-39.8); most had progression-free survival at 6 (90%) and 12 months (80%). Results were consistent in the subgroup of 65 patients with the same pre/post background treatment. Nearly all patients had improved carcinoid syndrome symptoms, stable or improved weight and ECOG performance status. CONCLUSION: Patients showed improvements in clinical outcomes and indicators of overall health following treatment with telotristat ethyl in this exploratory pilot study, consistent with previously observed reductions in tumor size.