Satisfaction With and Adherence to Off-Label Corticosteroids in Adolescents and Adults With Eosinophilic Esophagitis: Results of a Web-Based Survey in the United States.

GOALS: We assessed satisfaction with and adherence to off-label corticosteroids in patients with eosinophilic esophagitis (EoE) in the United States. BACKGROUND: EoE is a chronic inflammatory disease for which there are currently no US Food and Drug Administration-approved swallowed topical corticosteroids. STUDY: This noninterventional, cross-sectional, web-based survey included caregivers of adolescents (aged 11 to 17 y) and adults (aged 18 years or older) with a self-reported [or caregiver-reported (adolescents)] physician diagnosis of EoE who were receiving corticosteroids. Participants were recruited through 2 nonprofit, patient advocacy groups. The 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) was used to assess satisfaction across effectiveness, convenience, and global satisfaction domains (scale: 1 to 100 per domain); higher scores indicated greater satisfaction. The 4-item Morisky Green Levine Medication Adherence Scale (MGL-4) was used to assess adherence; an MGL-4 score of <3 indicated adherence. Participants also reported reasons for nonadherence. RESULTS: Overall, 201 participants (caregivers of adolescents, n=98; adults, n=103) were included in this study. Mean TSQM-9 scores indicated low satisfaction with off-label corticosteroids across all 3 satisfaction domains in adolescents (≤61.1) and adults (≤55.7). Slightly fewer adolescents (37.1%) than adults (40.8%) were considered adherent. Forgetfulness was the most frequently reported reason for nonadherence; some patients chose not to take their medications, owing to poor palatability (adolescents), difficulty taking medications at specific times (adults), or feeling depressed/overwhelmed (adolescents and adults). CONCLUSIONS: Satisfaction with and adherence to off-label corticosteroids were low in this web-based survey of adolescents and adults with EoE in the United States.

Qualitative assessment of the suitability of the Dysphagia Symptom Questionnaire to monitor dysphagia in children aged 7-10 years with eosinophilic esophagitis.

BACKGROUND: The Dysphagia Symptom Questionnaire (DSQ) is a patient-reported outcome measure that assesses the frequency and severity of dysphagia in patients with eosinophilic esophagitis (EoE); however, it has only been validated for use in patients with EoE aged 11-40 years. This study examined the content validity of the DSQ and its usability on an electronic handheld device in children aged 7-10 years with EoE. METHODS: In this qualitative, observational cohort study, participants were recruited to partake in two rounds of interviews. During visit 1, a cognitive interview examined EoE-associated concepts and the appropriateness of the DSQ for assessing dysphagia. Participants completed the DSQ daily for 2 weeks, and DSQ scores were calculated. After 2 weeks, a second interview assessed the usability of the DSQ on the electronic device and the burden associated with completing it daily. RESULTS: Overall, 16 participants were included (aged 7-8 years: n = 8; aged 9-10 years: n = 8); most were male (75%) and white (81%), and the mean (standard deviation [SD]) age was 8.4 (1.3) years. The most commonly reported EoE-associated concept was 'trouble with swallowing' (63% [10/16]). Most participants reported that the questions were 'easy to complete' and 'relevant to someone with EoE and dysphagia'. Overall, participants reported understanding the questions and associated responses; however, further probing demonstrated inconsistent comprehension. Key challenging concepts included 'solid food', 'trouble swallowing', 'vomit', and 'relief'; some participants also reported difficulty differentiating between pain levels (31% [4/13]). Most caregivers reported that their child had experienced dysphagia (94% [15/16]); however, mean (SD) DSQ scores over the study period were low (7.3 [7.4]), suggesting infrequent and mild dysphagia, or a lack of comprehension of the questions. Most participants reported that completing the DSQ on the electronic device was easy (93% [14/15]) and they would be willing to complete it for longer than 2 weeks (73% [11/15]). CONCLUSIONS: Difficulties with comprehension and comprehensiveness suggest that the DSQ may not be sufficiently comprehensive for use in all patients in this population, and wording/phrasing changes are required before use in a clinical trial setting.

Disease Burden and Treatment Patterns Associated With Eosinophilic Esophagitis in the United States: A Retrospective Claims Study.

GOALS: This US-based, retrospective claims study aimed to investigate disease burden and treatment patterns in patients with eosinophilic esophagitis (EoE), and to compare health care resource use (HCRU) in patients with EoE and matched controls without EoE. MATERIALS AND METHODS: Patients with a diagnosis of EoE and ≥12 months of prediagnosis data were identified from the Truven Health MarketScan Research databases (January 2008 to September 2016) and followed up from the diagnosis date until termination of eligibility for a health plan. Patient clinical characteristics and HCRU were recorded in the 12 months before diagnosis; HCRU and treatment patterns were recorded during follow-up. HCRU in patients with EoE and matched controls was compared during the 12-month postdiagnosis period. RESULTS: Among the 23,003 patients with EoE (mean age: 34.3 y; 64.8% male), gastroesophageal reflux disease was the most common prediagnosis condition (34.6%). After diagnosis, the most common off-label, first-line treatments were proton pump inhibitor monotherapy (52.8%) and topical corticosteroid monotherapy (21.5%). Overall, 3336 patients (14.5%) received at least 3 lines of off-label pharmacotherapy. Outpatient visits (recorded in 99.9% of patients on and postdiagnosis) were most frequently to gastroenterologists/pediatric gastroenterologists (49.5% prediagnosis, 72.6% on and postdiagnosis). Inpatient admissions and outpatient and emergency room visits were more likely in patients with EoE than in matched controls (P<0.0001). CONCLUSIONS: Patients with EoE in the USA experience a high disease burden both before and after diagnosis, which requires significant HCRU. Our findings highlight the unmet need for adequate control of EoE-related symptoms.

Impact on caregivers of adult patients receiving parenteral support for short-bowel syndrome with intestinal failure: A multinational, cross-sectional survey.

BACKGROUND: Patients with short-bowel syndrome and intestinal failure (SBS-IF) require parenteral support (PS) and may need long-term home-care support. This survey assessed the impact of care provision on adult caregivers of adult patients receiving PS for SBS-IF. METHODS: An online, cross-sectional survey of caregivers of adults with a self-reported physician diagnosis of SBS-IF was conducted in France, Germany, Italy, the UK, and USA. Impact on caregivers was evaluated using the 18-item Caregiver Strain Index (CSI), the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP), and self-reporting impact questionnaires. RESULTS: Caregivers (N = 121; aged 51 ± 13.7 years; 59% women) provided assistance for a mean of 9.9 ± 12.53 years; 77% were providing care 7 days per week. Patients (51 ± 16.4 years; 56% women) of caregivers were typically family members: spouse/partner (61%), adult son/daughter (19%), or parent (10%). Caregivers reported experiencing some strain (CSI score 4 ± 3.4). Among 71 of 73 employed caregivers, the WPAI:SHP assessment showed that caregivers missed 7% ± 12.7% of work hours in the preceding week and were present but not productive at work 37% ± 23.1% of the time; 28% of caregivers reported a reduced number of working hours because of caregiving. Many caregivers reported limitations in recreational activities (53%), and ≥30% had difficulty spending time with family and friends. Caregivers (87%) also reported worrying about the patient's health. CONCLUSIONS: Caregivers of adult patients with SBS-IF experience negative daily personal impacts and loss of productivity arising from their caregiving responsibilities.

Long-Term Treatment of Eosinophilic Esophagitis With Budesonide Oral Suspension.

BACKGROUND & AIMS: We evaluated treatment withdrawal, long-term outcomes, and safety of budesonide oral suspension (BOS) 2.0 mg twice daily in patients with eosinophilic esophagitis who completed a 12-week induction study. METHODS: Induction full responders (≤6 eosinophils per high-power field [eos/hpf] and ≥30% reduction in the Dysphagia Symptom Questionnaire score) to BOS 2.0 mg twice daily (ORBIT1/SHP621-301/NCT02605837) were randomized to continue BOS (BOS-BOS) or withdraw to placebo (BOS-PBO) for 36 weeks (ORBIT2/SHP621-302/NCT02736409). Induction partial responders and nonresponders, and patients who received induction placebo, received BOS for 36 weeks. The primary end point was the proportion of BOS-BOS and BOS-PBO patients who relapsed (≥15 eos/hpf and ≥4 days of dysphagia [Dysphagia Symptom Questionnaire] over 2 weeks) by week 36. The key secondary end point was the proportion of induction partial responders and nonresponders who fully responded after 52 weeks of total BOS therapy. Other secondary end points included the proportion of induction full responders with histologic responses (≤1, ≤6, <15 eos/hpf) at week 12 of the extension study, and safety outcomes. RESULTS: The randomized withdrawal period enrolled 48 patients (BOS-BOS, n = 25; BOS-PBO, n = 23); 106 induction partial responders and nonresponders, and 65 induction placebo patients received BOS. More BOS-PBO than BOS-BOS patients relapsed over 36 weeks (43.5% vs 24.0%; P = .131) and had histologic responses at week 12 of therapy (P < .001). Overall, 13.2% of induction partial responders and nonresponders fully responded at week 36. BOS was well tolerated; therapy duration was not associated with new safety concerns. CONCLUSIONS: For induction full responders, continuing BOS numerically improved maintenance of efficacy vs withdrawal. A longer therapy duration did not raise safety concerns. (ClinicalTrials.gov: NCT02736409.).

Documenting the Journey of Patients with Eosinophilic Esophagitis and the Impact of the Disease on Patients and their Caregivers: A Cross-sectional, Qualitative Research Study.

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated esophageal disease for which there is currently no approved treatment in the USA and only one approved therapy in Europe. EoE can significantly affect the lives of patients and caregivers; however, little has been published about patients' experiences from symptom onset to diagnosis and treatment. METHODS: This was a cross-sectional, qualitative research study. During one-on-one semi-structured interviews, patients with EoE in the USA and their caregivers provided information about their experiences of EoE before and during diagnosis, and their current experiences. Qualitative data were analyzed using a content analysis approach. RESULTS: The study included children aged 6-11 years with EoE (n = 4) and their caregivers (n = 4); adolescents aged 12-17 years with EoE (n = 7) and their caregivers (n = 7); and adults aged ≥ 18 years with EoE (n = 20). The diagnosis of EoE was often arduous and took many years. Patients and caregivers were frequently frustrated with the complexities of diagnosing EoE, which often involved multiple healthcare providers and procedures. Patients reported physical and psychosocial burdens associated with EoE before diagnosis, including interference with social activities, school, and work. Patients also reported feeling frustrated or anxious. These burdens frequently remained after diagnosis. Caregivers also reported anxiety and, in some cases, interference with their ability to work. CONCLUSION: This study of EoE describes the difficult journey faced by patients and their caregivers from symptom onset to diagnosis and beyond.

Short-term cost analysis of raltegravir versus atazanavir + ritonavir or darunavir + ritonavir for treatment-naive adults with HIV-1 infection in the United States.

METHODS: Ninety-six-week costs for antiretroviral drugs, adverse event management, and HIV care for individuals initiating RAL, ATV/r, or DRV/r as first-line therapy for HIV-1 infection were estimated using an economic model. Efficacy and safety data (mean CD4 cell count changes, discontinuation rates, grade 3/4 adverse event incidence) for each regimen through 96 weeks of treatment were taken from the ACTG 5257 clinical trial. Antiretroviral drug costs for each initial regimen and for each substitution regimen, as used by individuals who discontinued their initial regimen, were based on wholesale acquisition costs. Adverse event management costs and HIV care costs, stratified by CD4 cell count range, were taken from published sources and inflated to 2016 dollars. Scenario and sensitivity analyses were conducted to assess the robustness of the results. Cost outcomes were discounted at an annual rate of 3.0%. RESULTS: Total 96-week costs were $81,231 for RAL, $88,064 for ATV/r, and $87,680 for DRV/r, where differences were primarily due to lower antiretroviral drug costs for RAL than for ATV/r or DRV/r. These results were found to be robust in scenario and sensitivity analyses. CONCLUSIONS: Relative to the DRV/r and ATV/r regimens, the RAL regimen had the lowest cost for treatment-naive adults with HIV-1 infection in the United States.

Short-term cost and efficiency analysis of raltegravir versus atazanavir/ritonavir or darunavir/ritonavir for treatment-naive adults with HIV-1 infection in Spain.

INTRODUCTION: The AIDS Clinical Trial Group (ACTG) 5257 clinical trial showed that raltegravir (RAL) was superior to atazanavir/ritonavir (ATV/r) and darunavir/ritonavir (DRV/r), when used in combination with emtricitabine/tenofovir DF (FTC/TDF), in a 96-week composite endpoint combining virologic efficacy and tolerability for treatment-naive adults with HIV-1 infection. This study aimed to estimate the efficiency associated with these three regimens in Spain. METHODS: An economic model was developed to estimate costs for antiretroviral drugs, adverse event management, and HIV care for individuals initiating first-line therapy. Antiretroviral drug costs were based on hospital costs with mandatory discounts applied. Adverse event management costs and HIV care costs were obtained from published sources and inflated to 2015 euros. Head-to-head efficacy and safety data (discontinuation rates, mean CD4 cell-count changes, adverse event incidence) up to 96 weeks for each regimen were obtained from the clinical trial. The efficiency of each regimen, as measured by the cost per successfully treated patient (i.e. on first-line therapy for 96 weeks), was estimated and examined in sensitivity analyses. All cost outcomes were discounted at 3.0% annually. RESULTS: Total costs per successfully treated patient were €22,377 for RAL, €26,629 for ATV/r, and €23,928 for DRV/r. These results were found to be robust in sensitivity analyses. DISCUSSION: RAL has the lowest cost per successfully treated patient when compared with DRV/r and ATV/r, each used in combination with FTC/TDF, for treatment-naive adults with HIV-1 infection in Spain. This economic evidence complements the clinical benefits of RAL reported in the ACTG 5257 clinical trial.

Antiretroviral Treatment Switching and Its Association With Economic Outcomes and Adverse Treatment Effects Among Commercially Insured and Medicaid-Enrolled Patients With HIV in the United States.

BACKGROUND: Antiretroviral therapy (ART) of HIV typically involves the use of 2 nucleoside reverse transcriptase inhibitors plus a third agent (eg, protease inhibitor). It has been shown that over the course of treatment, a proportion of patients switch their ART for various reasons (eg, tolerability, long-term toxicities). We hypothesize that there is a relationship between ART treatment switching and economic and clinical outcomes among HIV patients. OBJECTIVE: To determine whether switching ART regimens is associated with greater health care costs, resource use, and adverse treatment effects. METHODS: Administrative health care claims were used to identify commercially insured and Medicaid-enrolled patients in the United States who had ≥2 claims containing an HIV/AIDS diagnosis from 2006 to 2011 and received an ART prescription from 2007 to 2010. The final population included patients who were ≥18 years old on their index date (ie, date of first ART prescription) and had continuous health plan enrollment for ≥12 months before and after their index date. Treatment characteristics (eg, switching), adverse treatment effects, and health care resource utilization and costs, were evaluated during a 12-month follow-up period. Multivariable models assessed the relationship between ART switching and economic outcomes (ie, costs, number of health care encounters) and adverse treatment effects. RESULTS: A total of 14 590 commercially insured patients met all inclusion criteria and 12% had an ART switch; further, 5744 Medicaid-enrolled patients met all inclusion criteria, and 14% switched treatment. After adjusting for confounders, ART switching was associated with 64% and 36% (P < 0.0001) increases in hospitalizations, 36% and 25% (P < 0.0001) increases in nonpharmacy costs, and 15% and 18% (P < 0.0001) increases in pharmacy costs, among commercially insured and Medicaid-enrolled patients, respectively. ART switching increased the risk of adverse treatment effects, overall and for specific conditions of interest (eg, gastrointestinal intolerance). CONCLUSIONS: This study suggests that ART switching is associated with economic outcomes and certain adverse treatment effects. Efforts to put patients on an optimal ART regimen initially, therefore reducing the need for subsequent switching, may have a positive effect on patients specifically and the health care system in general.

Migraine-related healthcare resource use and costs for subjects prescribed fixed-dose combination sumatriptan/naproxen sodium vs. single-entity oral triptans in a managed care population in the USA.

BACKGROUND: Randomized clinical trials have demonstrated that the efficacy of a fixed-dose single-tablet combination containing sumatriptan and naproxen sodium (S/NS) was greater than either of its individual components. Simplifying drug regimens (e.g., via a fixed-dose combination) has been shown to improve "real-world" outcomes by reducing pill burden and treatment regimen complexity, improving adherence, and reducing healthcare resource use and associated costs; however, no studies assessing such outcomes have been conducted to date for the acute treatment of migraine. OBJECTIVE: To assess migraine-related healthcare resource use and associated costs for subjects prescribed S/NS vs. subjects prescribed single-entity oral triptans (SOTs) within a managed care population in the USA. METHODS: In this retrospective analysis of administrative claims data from July 1, 2008 to December 31, 2009 (IMS LifeLink), subjects meeting the following criteria were selected: one or more pharmacy claim(s) for either S/NS or SOT (index date), aged 18-64 years; at least one migraine diagnosis, and continuous enrollment in the 6 months prior to and post the index date. The study population was subsequently stratified for two analyses: triptan-naïve (triptan naïve in the 6-month period prior to the index date) and triptan-switch (triptan user in the 6-month period prior to the index date and switching to another triptan). Subjects prescribed S/NS were propensity-score matched with subjects prescribed SOT (triptan-naïve analysis: 1:3; triptan-switch analysis: 1:1) to assess differences in healthcare resource use and associated costs (2009 US$) between the S/NS and SOT groups. RESULTS: Results from the triptan-naïve and triptan-switch analyses suggest that subjects prescribed S/NS are likely to have similar healthcare resource use patterns as those either newly initiated on an SOT or switching SOTs, as measured by migraine medication use, migraine-related healthcare resource use, and all-cause healthcare resource use. One exception was the observed increased use of opioids in the SOT group compared with the S/NS group (change in mean number of tablets pre-index vs. post-index, S/NS vs. SOT; triptan-naïve analysis: 8.6 vs.18.3, p = 0.045; triptan-switch analysis: -8.2 vs. 17.7; p = 0.120). Total costs from the triptan-naïve analysis indicated that the S/NS group had lower migraine-related (US$744 vs. US$820; p = 0.067) and all-cause healthcare costs (US$4,391 vs. US$4,870; p = 0.040) when compared with the SOT group, driven by savings in medical costs (migraine-related: US$252 vs. US$380; p = 0.001; all-cause: US$3,023 vs. US$3,599; p = 0.014). However, no significant differences were observed for total costs from the triptan-switch analysis (migraine-related healthcare costs, S/NS vs. SOT: US$1,159 vs. US$1,117; p = 0.929; all-cause healthcare costs: US$5,128 vs. US$4,788; p = 0.381). CONCLUSION: Study results suggest similar healthcare resource use patterns and associated costs when comparing S/NS and SOT across a triptan-naïve and triptan-experienced population. While the current study focuses on direct medical costs, future studies should extend beyond such a perspective to explore functional status, productivity, and health-related quality of life and satisfaction, attributes not captured in administrative claims data, but nonetheless important treatment goals.

Clinical progression, acute urinary retention, prostate-related surgeries, and costs in patients with benign prostatic hyperplasia taking early versus delayed combination 5α-reductase inhibitor therapy and α-blocker therapy: a retrospective analysis.

BACKGROUND: Two previous retrospective database analyses compared early combination therapy with an α-blocker (AB) and 5-α reductase inhibitor (5-ARI) to delayed combination therapy and found that patients receiving the delayed combination therapy were more likely to have clinical progression, acute urinary retention (AUR), and surgery. Although these studies indicate the clinical benefits of early treatment, both studies failed to take into account important baseline clinical measures, such as prostate-specific antigen (PSA) values. OBJECTIVE: This study was designed to compare clinical and cost differences in men with benign prostatic hyperplasia (BPH) who initiated early versus delayed combination therapy with a 5-ARI + an AB, factoring in baseline PSA values. METHODS: This retrospective claims data analysis assessed data from >14 million US men with linked medical data, pharmacy data, laboratory results, and enrollment information from January 1, 2000, to December 31, 2009. Men aged 50 or older and treated for BPH with a 5-ARI + an AB were identified. Patients were required to be eligible for services at least 6 months before and 12 months after the index medication date. Patients were assigned to 1 of 2 treatment groups based on therapy (early or delayed) and 3 cohorts based on availability of PSA laboratory values (patients with a PSA value, patients with a PSA value >1.5 and <10, and all patients). Using a logistic model, the likelihood of clinical progression (defined as the occurrence of AUR or prostate surgery) during the 12 months after the date of first prescription fill was compared between BPH patients receiving early versus delayed combination therapy. BPH-related medical costs (excluding pharmacy costs) were assessed using generalized linear models. RESULTS: Among the 13,551 patients identified for study inclusion, the highest risks for clinical progression, AUR, and prostate-related surgery were consistently demonstrated in patients with a PSA >1.5 and <10. Across all 3 cohorts, the delayed combination-treatment group was more likely to have clinical progression, AUR, and prostate-related surgeries versus the early combination-treatment group. The incremental difference in BPH-related costs between the delayed and early combination-treatment groups was $190 per patient overall; the greatest incremental difference ($397) was observed in patients with PSA >1.5 and <10. CONCLUSIONS: The results suggest that early initiation of combination therapy with 5-ARI + an AB, compared with delayed initiation, can reduce the risks for clinical progression, AUR, and prostate-related surgeries, as well as BPH-related medical costs, in patients with BPH.

Evaluation of recent trends in treatment patterns among men with benign prostatic hyperplasia.

Although there is an abundance of evidence regarding clinical efficacy and safety of benign prostatic hyperplasia (BPH) treatment, real-world evidence is lacking for pharmacotherapy utilization and trends. It is unclear how evidence demonstrating the efficacy of combination 5-alpha reductase inhibitors and alpha blockers for improving symptoms and reducing risk of disease progression translates into real-world practice for the treatment of BPH. A retrospective study of a database was conducted to describe pharmacotherapy utilization/trends in the treatment of BPH among patients in the managed care setting. After inclusion and exclusion criteria were applied, the final sample size was 107,038. The proportion of patients with BPH receiving 5-alpha reductase inhibitors therapy increased (21.1% in 2003 to 30.5% in 2007), as did the proportion receiving combination therapy (10.7% and 16.1%, respectively). We observed an almost 50% increase in 5-alpha reductase inhibitors use over 5 years and a 60% increase in the use of combination 5-alpha reductase inhibitors/alpha blockers therapy.