Economic Burden of Irritable Bowel Syndrome with Diarrhea: Retrospective Analysis of a U.S. Commercially Insured Population.

BACKGROUND: The economic burden associated with irritable bowel syndrome with diarrhea (IBS-D) is not well understood. OBJECTIVES: To (a) evaluate total annual all-cause, gastrointestinal (GI)-related, and symptom-related (i.e., IBS, diarrhea, abdominal pain) health care resource use and costs among IBS-D patients in a U.S. commercially insured population and (b) estimate incremental all-cause health care costs of IBS-D patients versus matched controls. METHODS: Patients aged ≥ 18 years with 12 months of continuous medical and pharmacy benefit eligibility in 2013 were identified from the Truven Health MarketScan research database. The study sample included patients with ≥ 1 medical claim with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code in any position for IBS (ICD-9-CM 564.1x) and either (a) ≥ 2 claims for diarrhea (ICD-9-CM 787.91, 564.5x) on different service dates in 2013, or (b) ≥ 1 claim for diarrhea plus ≥ 1 claim for abdominal pain (ICD-9-CM 789.0x) on different service dates in 2013, or (c) ≥ 1 claim for diarrhea plus ≥ 1 pharmacy claim for a symptom-related prescription on different service dates in 2013. Controls included patients with no claims for IBS, diarrhea, abdominal pain, or symptom-related prescriptions in 2013. Controls were randomly selected and matched with IBS-D patients in a 1:1 ratio based on age (± 4 years), gender, geographic location, and health plan type. All-cause health care resource utilization included medical and pharmacy claims for health care services associated with any condition. Total health care costs were defined as the sum of health plan-paid and patient-paid direct health care costs from prescriptions and medical services, including inpatient, emergency department (ED), and physician office visits, and other outpatient services. A total cost approach was used to assess all-cause, GI-related, and symptom-related health care costs for IBS-D patients. An incremental cost approach via generalized linear models was used to assess the excess all-cause costs attributable to IBS-D after adjusting for demographics and general and GI comorbidities. RESULTS: Of 39,306 patients (n = 19,653 each for IBS-D and matched controls) included, mean (± SD) age was 47 (± 17) years and 76.5% were female. Compared with controls, IBS-D patients had a significantly higher mean annual number of hospitalizations, ED visits, office visits, and monthly (30-day) prescription fills. Mean annual all-cause health care costs for IBS-D patients were $13,038, with over half (58.4%) attributable to office visits and other outpatient services (e.g., diagnostic tests and laboratory or radiology services), and remaining costs attributable to prescriptions (19.5%), inpatient admissions (13.6%), and ED visits (8.5%). GI-related ($3,817) and symptom-related ($1,693) costs were also primarily driven by other outpatient service costs. After adjusting for demographics and comorbidities, incremental annual all-cause costs associated with IBS-D were $2,268 ($9,436 for IBS-D patients vs. $7,169 for matched controls; P < 0.001) per patient/year, of which 78% were from medical costs and 22% were from prescription costs. CONCLUSIONS: IBS-D was associated with a substantial burden in direct costs in this population. Compared with matched controls, IBS-D patients had greater medical service use and incurred significantly more annual all-cause health care costs, even after controlling for demographics and comorbidities. Incremental costs associated with IBS-D were primarily attributable to increased use of medical services rather than pharmacy costs. DISCLOSURES: This study was funded by Allergan. The authors received no compensation related to the development of the manuscript. Buono and Andrae are employees of Allergan. Mathur is an employee of Axtria. Averitt was an employee of Axtria at the time this study was conducted. Data from this manuscript have previously been presented in poster format by Buono at the American College of Gastroenterology Annual Scientific Meeting; Honolulu, Hawaii; October 16-21, 2015. Mathur and Averitt were involved in conducting the study analyses. All authors were involved in the study design, interpretation of the data, and preparation of the manuscript. The authors take full responsibility for the scope, direction, and content of the manuscript and have approved the submitted manuscript.

Health-related quality of life, work productivity, and indirect costs among patients with irritable bowel syndrome with diarrhea.

BACKGROUND: Irritable bowel syndrome (IBS) affects 10-15% of adults in the US, and is associated with significant impairment in health-related quality of life (HRQoL); however, information specific to the diarrhea subtype (IBS-D) is lacking. We assessed the impact of IBS-D on HRQoL, work productivity, and daily activities, and the associated indirect costs, among a sample of the US population. METHODS: Respondents (≥18 years) from the 2012 US National Health and Wellness Survey who reported an IBS-D diagnosis by a physician or symptoms consistent with Rome II criteria for IBS-D were identified as having IBS-D. Controls included respondents without IBS-D or inflammatory bowel disease. HRQoL was assessed via the Short Form 36 Health Survey version 2 questionnaire and summarized into Mental and Physical Component Summary (MCS; PCS) scores and a Short Form-6 dimension (SF-6D) utility score. Work and activity impairment were assessed via the Work Productivity and Activity Impairment Questionnaire: General Health version (WPAI:GH), which measures absenteeism, presenteeism, overall work productivity loss, and daily activity impairment. Indirect costs were calculated using unit cost data from the Bureau of Labor Statistics and variables from the WPAI:GH. Generalized linear models were used to examine differences in health outcomes between respondents with IBS-D and controls, controlling for demographic and health characteristics. RESULTS: In total, 66,491 respondents (1102 IBS-D; 65,389 controls) were analyzed. Mean age was 48.7 years; 50% were female. Compared with controls, the IBS-D cohort reported significantly lower HRQoL (mean MCS: 45.16 vs. 49.48; p < 0.001; mean PCS: 47.29 vs. 50.67; p < 0.001; mean SF-6D: 0.677 vs. 0.741; p < 0.001) and greater absenteeism (5.1% vs. 2.9%; p = 0.004), presenteeism (17.9% vs. 11.3%; p < 0.001), overall work productivity loss (20.7% vs. 13.2%; p < 0.001), and activity impairment (29.6% vs. 18.9%; p < 0.001). Respondents with IBS-D also incurred an estimated $2486 more in indirect costs ($7008 vs. $4522; p < 0.001). CONCLUSIONS: Compared with controls, IBS-D is associated with significantly lower HRQoL, greater impairments in work and daily activities, and higher indirect costs, imposing a substantial burden on patients and employers. These findings suggest a significant unmet need exists for effective IBS-D treatments.

Economic burden of inadequate symptom control among US commercially insured patients with irritable bowel syndrome with diarrhea.

AIMS: To assess healthcare resource use and costs among irritable bowel syndrome (IBS) with diarrhea (IBS-D) patients with and without evidence of inadequate symptom control on current prescription therapies and estimate incremental all-cause costs associated with inadequate symptom control. METHODS: IBS-D patients aged ≥18 years with ≥1 medical claim for IBS (ICD-9-CM 564.1x) and either ≥2 claims for diarrhea (ICD-9-CM 787.91, 564.5x), ≥1 claim for diarrhea plus ≥1 claim for abdominal pain (ICD-9-CM 789.0x), or ≥1 claim for diarrhea plus ≥1 pharmacy claim for a symptom-related prescription within 1 year of an IBS diagnosis were identified from the Truven Health MarketScan database. Inadequate symptom control, resource use, and costs were assessed up to 1 year following the index date. Inadequate symptom control included any of the following: (1) switch or (2) addition of new symptom-related therapy; (3) IBS-D-related inpatient or emergency room (ER) admission; (4) IBS-D-related medical procedure; (5) diagnosis of condition indicating treatment failure; or (6) use of a more aggressive prescription. Generalized linear models assessed incremental costs of inadequate symptom control. RESULTS: Of 20,624 IBS-D patients (mean age = 48.5 years; 77.8% female), 66.4% had evidence of inadequate symptom control. Compared to those without inadequate symptom control, patients with evidence of inadequate symptom control had significantly more hospitalizations (12.0% vs 6.0%), ER visits (37.1% vs 22.6%), use of outpatient services (73.0% vs 60.7%), physician office visits (mean 11.0 vs 8.1), and prescription fills (mean 40.0 vs 26.7) annually (all p < .01). Incremental costs associated with inadequate symptom control were $3,065 (2013 US dollars), and were driven by medical service costs ($2,391; 78%). LIMITATIONS: Study included US commercially insured patients only and inferred IBS-D status and inadequate symptom control from claims. CONCLUSIONS: Inadequate symptom control associated with available IBS-D therapies represents a significant economic burden for both payers and IBS-D patients.

Impact of linaclotide treatment on work productivity and activity impairment in adults with irritable bowel syndrome with constipation: results from 2 randomized, double-blind, placebo-controlled phase 3 trials.

BACKGROUND: Irritable bowel syndrome with constipation (IBS-C), a chronic functional gastrointestinal disorder, has been shown to negatively affect work productivity and impair daily activity, resulting in a substantial burden for patients and employers. Linaclotide is a first-in-class guanylate cyclase-C agonist approved for the treatment of adults with IBS-C and chronic idiopathic constipation in the United States. OBJECTIVE: To analyze the impact of treatment with linaclotide on work productivity and daily activity impairment in adults with IBS-C and estimate the indirect costs associated with this condition. METHODS: This was a post-hoc analysis of data on IBS-C-related work time missed and work and activity impairment from 2 phase 3 clinical trials that assessed the efficacy and safety of linaclotide therapy in adults with IBS-C. The Work Productivity and Activity Impairment Questionnaire for IBS-C (WPAI:IBS-C) was self-administered at baseline and at weeks 4, 8, and 12 during the 12-week treatment periods in Trials 1 and 2 and at weeks 16, 20, and 26 during the extended treatment period in Trial 2. An analysis of covariance was conducted to assess changes from baseline to all study weeks for each WPAI:IBS-C measure. Indirect costs were calculated by converting overall work productivity losses into monetary values using the human capital cost approach. RESULTS: Of the 1602 patients with IBS-C who were randomized in the 2 clinical trials, 1555 (97.1%) completed a baseline and at least 1 postbaseline WPAI:IBS-C assessment and were included in the analysis cohort; 1148 (71.7%) of these patients were employed. Once-daily treatment with linaclotide significantly reduced overall work productivity loss and daily activity impairment among patients with IBS-C at all study weeks. From baseline to week 12, compared with placebo, linaclotide significantly reduced presenteeism by 5.2%, overall work productivity loss by 6.1%, and daily activity impairment by 4.7% (all P <.01) and led to a numerically greater decrease in absenteeism. From baseline to week 26, compared with placebo, reductions with linaclotide were 5.9% for presenteeism, 7.5% for overall work productivity loss, and 6.7% for daily activity impairment (all P <.05). Reductions in overall work productivity loss from baseline to week 26 translate to 103 hours to 156 hours annually and correspond to an avoided overall work loss of $3209 to $4861 annually for an employee with IBS-C. CONCLUSION: The results of this analysis indicate that appropriate treatment of IBS-C with medications such as linaclotide can reduce work-related impairment associated with IBS-C. In addition, IBS-C therapies that effectively manage this chronic condition and improve employees' quality of life and work productivity may represent significant cost-savings for employers in the form of avoided work productivity losses.

Economic burden of irritable bowel syndrome with constipation: a retrospective analysis of health care costs in a commercially insured population.

BACKGROUND: The prevalence of irritable bowel syndrome with constipation (IBS-C) is estimated to be between 4.3% and 5.2% among adults in the United States. Little is known about the health care resource utilization and costs associated with IBS-C. OBJECTIVES: To (a) evaluate the annual total all-cause, gastrointestinal (GI)-related, and IBS-C-related health care costs among IBS-C patients seeking medical care in a commercially insured population and (b) estimate the incremental all-cause health care costs among IBS-C patients relative to matched controls. METHODS: Patients aged ≥ 18 years with continuous medical and pharmacy benefit eligibility in 2010 were identified from the HealthCore Integrated Research Database, which consists of administrative claims from 14 geographically dispersed U.S. health plans representing 45 million lives. IBS-C patients were defined as those with ≥ 1 medical claim with an ICD-9-CM diagnosis code in any position for IBS (ICD-9-CM 564.1x) and either ≥ 2 medical claims for constipation (ICD-9-CM 564.0x) on different service dates or ≥ 1 medical claim for constipation plus ≥ 1 pharmacy claim for a constipation-related prescription on different dates of service during the study period. Controls were defined as patients without any medical claims for IBS, constipation, abdominal pain, or bloating or pharmacy claims for constipation-related prescriptions. Controls were randomly selected and matched with IBS-C patients in a 1:1 ratio based on age (± 4 years), gender, health plan region, and health plan type. Patients with diagnoses or prescriptions suggesting mixed IBS, IBS with diarrhea, chronic diarrhea, or drug-induced constipation were excluded. Total health care costs in 2010 U.S. dollars were defined as the sum of health plan and patient paid costs for prescriptions and medical services, including inpatient visits, emergency room (ER) visits, physician office visits, and other outpatient services. The total cost approach was used to assess total all-cause or disease-specific health care costs for patients with IBS-C, while the incremental cost approach was used to examine the excess all-cause costs of IBS-C by comparing IBS-C patients with matched controls. Generalized linear models with bootstrapping were used to assess the incremental all-cause costs attributable solely to IBS-C after adjusting for demographics, Elixhauser Comorbidity Index (ECI) score, and other general and GI-related comorbidities not included in the ECI score. RESULTS: A total of 7,652 patients (n = 3,826 each in the IBS-C and control cohorts) were included in the analysis. The mean (± SD) age was 48 (± 17) years, and 83.6% were female. The mean annual all-cause health care costs for IBS-C patients were $11,182, with over half (53.7%) of the costs attributable to outpatient services, including physician office visits and other outpatient services (13.1% and 40.6%, respectively). Remaining total all-cause costs were attributable to hospitalizations (21.8%), prescriptions (19.1%), and ER visits (5.4%). GI-related costs ($4,456) comprised 39.8% of total all-cause costs, while IBS-C-related costs ($1,335) accounted for 11.9% and were primarily driven by costs of other outpatient services (50.3%). After adjusting for demographics and comorbidities, the incremental annual all-cause health care costs associated with IBS-C were $3,856 ($8,621 for IBS-C patients vs. $4,765 for controls, P less than 0.01) per patient per year, of which 78.1% of the incremental costs were due to medical services, and 21.9% were due to prescription fills. CONCLUSIONS: IBS-C imposes a substantial economic burden in terms of direct health care costs in a commercially insured population. Compared with matched controls, IBS-C patients incurred significantly higher total annual all-cause health care costs even after controlling for general and GI-related comorbidities. Incremental all-cause costs associated with IBS-C were mainly driven by costs related to more frequent use of medical services as opposed to prescriptions.

Healthcare costs among patients with chronic constipation: a retrospective claims analysis in a commercially insured population.

OBJECTIVE: To evaluate total annual all-cause, gastrointestinal-related, and symptom-related healthcare costs among chronic constipation (CC) patients and estimate incremental all-cause healthcare costs of CC patients relative to matched controls. METHODS: Patients aged ≥18 years with continuous medical and pharmacy benefit eligibility in 2010 were identified from the HealthCore Integrated Research Database. CC patients had ≥2 medical claims for constipation (ICD-9-CM code 564.0x) ≥90 days apart or ≥1 medical claim for constipation plus ≥1 constipation-related pharmacy claim ≥90 days apart, and no medical claims for irritable bowel syndrome (IBS). Sub-groups with and without abdominal symptoms were classified according to the presence/absence of abdominal pain (ICD-9-CM code 789.0x) and bloating (ICD-9-CM code 787.3x). Controls without claims for constipation, abdominal pain, bloating, or IBS or constipation-related prescriptions were randomly selected and matched 1:1 with CC patients on age, gender, health plan region, and plan type. Generalized linear models with bootstrapping evaluated incremental all-cause costs attributable to CC, adjusting for demographics and comorbidities. RESULTS: Overall, 14,854 patients (n = 7427 each in CC and control groups) were identified (mean age = 59 years; 75.4% female). Mean annual all-cause costs for CC patients were $11,991 (2010 USD), with nearly half (44.8%) attributable to outpatient services, including physician office visits and other outpatient services (10.0% and 34.8%, respectively). GI-related costs comprised 33.7% of total all-cause costs. Symptom-related costs accounted for 10.5%, primarily driven by costs of other outpatient services (50.6%). Adjusted incremental all-cause costs associated with CC were $3508 per patient per year ($4446 for CC with abdominal symptoms; $2783 for CC without abdominal symptoms), of which 81.0% were from medical services. Incremental cost estimates may be over- or under-estimated due to classification based on claims. CONCLUSIONS: CC imposes a substantial burden in direct healthcare costs in a commercially insured population, mainly attributable to greater use of medical services.

Systematic review and meta-analysis of the efficacy of cardioversion by vernakalant and comparators in patients with atrial fibrillation.

PURPOSE: Rate and rhythm control are two well established treatment objectives for atrial fibrillation (AF) patients. While symptom reduction is a primary treatment goal, therapeutic practice related to cardioversion varies by region and patient, with several precautions associated with the use of current therapies. No comprehensive literature review on the relative efficacy of existing cardioversion approaches compared to newly available therapies has been conducted. METHODS AND RESULTS: A systematic literature review and meta-analysis were undertaken to evaluate the efficacy of pharmacologic therapies in eliciting cardioversion within 2 and 8-24 h among patients with recent-onset, short duration AF. Eligible studies included randomized controlled trials in which cardioversion rates were evaluated in at least 2 treatment groups. Bayesian mixed-treatment comparisons estimated odds ratios (95% credible intervals) for successful cardioversion. Results within 2 h showed vernakalant IV, propafenone IV and flecainide (IV and oral) were more efficacious in pair-wise comparisons to placebo. Results were mixed in analyses comparing efficacy rates between 8 and 24 h. Few adverse events were reported, with the most common being bradycardia and hypotension. CONCLUSIONS: In pair-wise comparisons of active treatment arms to one another, results suggest vernakalant IV, propafenone IV and flecainide appear to be effective in achieving rapid cardioversion in patients with short duration AF compared to other agents. Application of these findings to clinical practice need to account for the variable comorbidity profiles of patients, important determinants in the selection of appropriate therapy for individual patients. Though best practice methods were used, further research comparing treatments through direct head-to-head comparisons may be warranted to confirm these findings and further inform clinical practice.