Health utilities and quality-adjusted life years for patients with amyotrophic lateral sclerosis receiving reldesemtiv or placebo in FORTITUDE-ALS.

AIMS: To estimate the health utilities and quality-adjusted life years (QALYs) in patients with amyotrophic lateral sclerosis (ALS) receiving reldesemtiv versus placebo in FORTITUDE-ALS. MATERIALS AND METHODS: We performed a post hoc analysis of clinical trial data from FORTITUDE-ALS (NCT03160898). This Phase IIb, double-blind, randomized, dose-ranging, placebo-controlled, parallel-group, 12-week trial evaluated reldesemtiv in patients with ALS. Health utilities from the five-level version of the EuroQol five-dimensional questionnaire (EQ-5D-5L) were estimated using ALS Functional Rating Scale-Revised (ALSFRS-R) scores collected during the trial. QALYs were estimated using the area under the curve method. RESULTS: The full analysis set consisted of 456 patients (reldesemtiv n = 342, placebo n = 114), who received at least one dose of the double-blind study drug, and had ALSFRS-R assessed at baseline and at least one post-baseline assessment. The difference in EQ-5D-5L utility least-squares (LS) mean change from baseline to week 12 for reldesemtiv versus placebo, adjusted for baseline values, was statistically significant (0.03, 95% confidence interval [CI]: 0.01, 0.05; p = .0008). The incremental QALY of reldesemtiv versus placebo adjusted for baseline utility values showed a modest, but statistically significant, difference (0.004, 95% CI: 0.001, 0.007; p = .0058). CONCLUSIONS: This post hoc analysis of FORTITUDE-ALS suggests that reldesemtiv showed a modest but significant benefit in health utilities and QALYs compared with placebo. Future long-term studies that include direct collection of EQ-5D-5L data will be needed to confirm our findings. CLINICALTRIALS.GOV IDENTIFIER: NCT03160898.

MiToS and King's staging as clinical outcome measures in ALS: a retrospective analysis of the FORTITUDE-ALS trial.

OBJECTIVE: To evaluate the Milano-Torino staging (MiToS) and King's staging systems as potential outcome measures for clinical trials in amyotrophic lateral sclerosis (ALS) by assessing these outcomes in FORTITUDE-ALS. METHODS: This was a post hoc analysis of the phase 2b FORTITUDE-ALS trial (NCT03160898), a double-blind, randomized, dose-ranging, placebo-controlled, parallel-group study of reldesemtiv in patients with ALS. The treatment period was 12 weeks, with a follow-up assessment at week 16. Patients were retrospectively classified into MiToS and King's stages. Outcomes were the mean time maintaining baseline stage and risk of progression from the baseline stage to a later stage. RESULTS: The full analysis set consisted of 456 patients randomized 3:1 (reldesemtiv n = 342, placebo n = 114) who received at least one dose of double-blind study drug and had at least one post-baseline assessment. At baseline, MiToS and King's stages were balanced between the reldesemtiv and placebo groups: >99% of patients were in MiToS stage 0 or 1 and King's stage 1, 2 or 3. Time of maintaining the baseline stage was similar in both groups, for each staging system. The two staging systems exhibited considerably disparate results for risk of progression from baseline to a later stage: hazard ratio (HR) = 0.62 (95% confidence interval [CI] 0.38, 0.99) for MiToS and HR = 0.96 (95% CI 0.63, 1.44) for King's. CONCLUSION: This exploratory analysis showed the feasibility of MiToS and King's staging as potential outcome measures in ALS. Additional studies of these staging systems are needed to further explore their utility in ALS clinical trials.

Costs and Healthcare Resource Utilization for Obstructive Hypertrophic Cardiomyopathy With Septal Reduction Therapy.

BACKGROUND: Patients with obstructive hypertrophic cardiomyopathy (oHCM) and severe refractory symptoms may require invasive septal reduction therapies (SRTs), either surgical septal myectomy (SM) or transcatheter alcohol septal ablation (ASA). The main objective of this study was to quantify all-cause and oHCM-related healthcare resource utilization (HCRU) and costs for patients receiving SM or ASA. METHODS: This retrospective study utilized medical and pharmacy claims submitted during 2012-2020. HCRU and costs for 119 adults with oHCM who had at least 1 SM (n = 95) or ASA (n = 24) were compared for baseline and follow-up periods. RESULTS: The mean inpatient hospitalization stay was longer for SM (8.3 days) than ASA (6.0 days). Postprocedure HCM-related medication usage was greater following SM (98%) than ASA (88%). The mean number of HCM-related outpatient visits increased from pre- to post procedure (12.2 vs 15.9 in the SM group; 7.2 vs 9.5 in the ASA group), with most patients having at least 1 cardiology visit post procedure (86% of the SM group; 83% of the ASA group). Total mean HCM-related costs (reported in United States currency) increased with both procedures ($27,045 vs $119,772 in the SM group; $11,278 vs $54,351 in the ASA group), driven by increased inpatient hospitalization ($10,325 vs $112,923 in the SM group; $5509 vs $47,450 in the ASA group) and surgical costs ($6665 vs $92,031 in the SM group; $52 vs $44,815 in the ASA group). CONCLUSIONS: Our results indicate increasing costs for patients undergoing SRT, driven by inpatient hospitalizations and surgical costs. Commercially insured and Medicare Advantage patients with oHCM experience high healthcare costs and economic burden attributable to SRT.

Clinical Characteristics and Healthcare Resource Utilization among Patients with Obstructive Hypertrophic Cardiomyopathy Treated in a Range of Settings in the United States.

Obstructive hypertrophic cardiomyopathy (oHCM) has been studied primarily in comprehensive centers of excellence. Broadening the understanding of patients with oHCM in the general population may improve identification and treatment in other settings. This retrospective cohort study identified adults with oHCM from a large electronic medical record database comprising data from 39 integrated delivery networks (IBM Explorys; observational period: January 2009-July 2019). Clinical characteristics, healthcare resource utilization (HCRU), and outcomes were reported. Of 8791 patients, 53.0% were female and the mean index age was 61.8 years. Cardiovascular drugs prescribed included beta-blockers (80.5%), calcium channel blockers (46.0%), and disopyramide (2.4%). Over time, heart failure, atrial fibrillation, and ventricular arrhythmias increased. Surgical procedures included septal myectomy (22.0%), alcohol septal ablation (0.6%), and heart transplantation (0.3%). Implantable cardioverter defibrillators were present in 11.2% of patients. After initial septal reduction therapy (SRT), HCRU increased and 550 patients (27.7%) required a reintervention. Of the overall group, 2.7% experienced sudden cardiac arrest by end of study. In conclusion, this cohort of patients with oHCM had guideline-recommended drug therapy and procedures. Despite this, heart failure, atrial fibrillation, and ventricular arrhythmias increased, and more than a quarter of patients undergoing SRT required reintervention. These unresolved issues emphasize the unmet need for new, effective therapies for patients with oHCM.

Thirty-Day and 90-Day Episode of Care Spending Following Heart Failure Hospitalization Among Medicare Beneficiaries.

BACKGROUND: Despite growing interest in value-based models, utilization patterns and costs for heart failure (HF) admissions are not well understood. We sought to characterize Medicare spending for patients with HF for 30- and 90-day episodes of care (which include an index hospitalization and 30 or 90 days following discharge) and to describe the patterns of post-acute care spending. METHODS: Using Medicare fee-for-service administrative claims data from 2016 to 2018, we performed a retrospective analysis of patients discharged after hospitalization with primary discharge diagnoses of systolic HF, diastolic HF, hypertensive heart disease (HHD) with HF, and HHD with HF and chronic kidney disease. We analyzed coding patterns across these groups over time, median 30- and 90-day payments, and costs allocated to index hospitalization and postacute care. RESULTS: The study included 935 962 patients discharged following hospitalization for HF (systolic HF: 178 603; diastolic HF: 165 156; HHD with HF: 226 929; HHD with HF and chronic kidney disease: 365 274). The proportion of HHD codes increased from 26% of HF hospitalizations in 2016 to 91% in 2018. There was substantial spending on 30-day (median $13 330, interquartile range $9912-$22 489) and 90-day episodes (median $21 658, interquartile range $12 423-$37 630) for HF with significant variation, such that the third quartile of patients incurred costs 3 times the amount of the first quartile. Across all codes, the index hospitalization accounted for ≈70% of 30-day and 45% of 90-day spending. Sixty-one percent of postacute care spending occurred 31 to 90 days following discharge, with readmissions and observation stays (36%) and skilled nursing facilities (27%) comprising the largest categories. CONCLUSIONS: This patient episode-level analysis of contemporary Medicare beneficiaries is the first to examine 90-day spending, which will become an increasingly important pasyment benchmark with the expansion of the Medicare Bundled Payments for Care Improvement Program. Further investigation into the drivers of costs will be essential to provide high-value HF care.

Adverse drug effects across patients with heart failure: a systematic review.

OBJECTIVES: To summarize published literature on the incidence of adverse drug effects (ADEs) associated with guideline-directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF). STUDY DESIGN: Systematic literature review. METHODS: A systematic literature review was conducted in PubMed, Ovid MEDLINE, and Clinical Key covering January 1990 to December 2018. Key search terms were ADEs for ß-blockers (BBs), ACE inhibitors (ACEis), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs), and/or angiotensin receptor-neprilysin inhibitors (ARNis) in adult patients (≥ 18 years) with HFrEF. RESULTS: A total of 279 eligible articles were identified, of which 29 reported drug-related adverse effects and were included in this review. Of the 29 studies, 11 examined BBs; 9, MRAs; 6, ARNis; 2, ACEis; and 1, ARBs. The most common reported ADEs across these therapeutic classes included bradycardia, dizziness, hypotension, hyperkalemia, cough, and renal impairment. The incidence of BB-induced bradycardia was 1% to 52% based on 9 studies, and 6 studies described dizziness as a result of BBs and ARNis (15%-43%). Fourteen studies reported induced hypotension (1.4%-63%); 13 studies, hyperkalemia (0.6%-30.2%); 3 studies, cough (37%-50%); and 4 studies, renal impairment (0.6%-7.6%). CONCLUSIONS: Findings show that drug-related adverse effects are commonly reported in clinical trials and highlight the sizable burden of ADEs with medical therapy across patients with HFrEF. Additional real-world evidence and studies aiming to improve the tolerability of GDMT for patients with HFrEF are warranted.

Characteristics of Patients With Obstructive Hypertrophic Cardiomyopathy in Real-World Community-Based Cardiovascular Practices.

The clinical profile of patients with obstructive hypertrophic cardiomyopathy (oHC) is not well characterized, with little evidence outside selected referral populations. Using longitudinal medical claims data from a United States nationwide database, we retrospectively identified adults who were newly diagnosed with oHC. Clinical characteristics were compared from 1 year before diagnosis and at the 2-year follow-up. Patients (N = 1,841) with oHC (age 63 ± 15 years; 52% were male) with geographic representation across the United States were identified. Most patients received care within community-based cardiovascular practices and 7% at referral hypertrophic cardiomyopathy (HC) centers. Baseline diagnostic procedures included electrocardiogram (66%), echocardiogram (51%), magnetic resonance imaging (4%), and HC genetic testing (0.7%). Baseline co-morbidities were hypertension (59%), coronary artery disease (30%), diabetes (19%), and atrial fibrillation (19%). For all HC-related medications, use significantly increased after diagnosis. During follow-up, 144 patients (8%) received an implantable cardioverter-defibrillator for sudden death prevention, 99 underwent septal myectomy (5%), and 24 underwent alcohol septal ablation (1%). By the 1-year follow-up, 2% of patients had sudden cardiac arrest and 26% had atrial fibrillation, and heart failure increased from 16% to 27%. In conclusion, in a community-based population of patients with oHC, patients' age at diagnosis of oHC was older than reported for referral populations and patients had a significant co-morbidity burden. Cardiovascular medication use was appropriate, but the rate of guideline-supported surgical procedures was low.

Clinical trajectory of patients with a worsening heart failure event and reduced ventricular ejection fraction.

BACKGROUND: Recent data suggest that patients with heart failure with reduced ejection fraction (HFrEF) and worsening heart failure (WHF) have potential for greater benefit from newer HF therapies. We investigated characteristics and outcomes of patients with HFrEF and WHF by severity of left ventricular dysfunction. METHODS: We identified patients with chronic symptomatic HFrEF (left ventricular ejection fraction [LVEF] ≤35%) and evidence of WHF (emergency department visit or hospitalization for acute HF within 12 months of index echocardiogram) treated at Duke University between 1/2009 and 12/2018. Patients were stratified by LVEF≤25% or 26% to35%. Cox models were used to estimate cause-specific hazard ratios and 5-year event incidence of death and hospitalization across the range of LVEF. RESULTS: Of 2823 patients with HFrEF and WHF, 1620 (57.4%) had an LVEF≤25% and 1203 (42.6%) had an LVEF 26% to35%. Compared to patients with LVEF 26% to35%, those with LVEF≤25% were younger and more commonly men with a lower cardiovascular comorbidity burden. Patients with LVEF≤25% were less commonly on beta blockers (85.9% vs 90.5%) but more commonly treated with mineralocorticoid receptor antagonists (49.3% vs 41.1%) and implantable defibrillators (41.3% vs 28.2%). Patients with LVEF≤25% had significantly higher hazards for death (HR 1.24 [95% CI 1.11 - 1.38]), all-cause hospitalization (HR 1.21 [95% CI 1.10 - 1.33]), and HF hospitalization (HR 1.25 [95% CI 1.1 - 1.38]) through 5-years. CONCLUSIONS: More than half of patients with chronic HFrEF and WHF have severe LV dysfunction. Important differences in comorbidities, HF therapies, and outcomes exist between those with LVEF≤25% and those with LVEF 26% to35%.

Healthcare resource utilization and cost of obstructive hypertrophic cardiomyopathy in a US population.

Background: There are limited data evaluating all-cause and disease-related healthcare resource utilization (HCRU) and cost of care for patients with obstructive hypertrophic cardiomyopathy (oHCM). Methods: This was a retrospective study using US longitudinal medical and pharmacy claims data during 2012-2020. Adults with ≥2 oHCM diagnoses were identified, with the first diagnosis date used as the index date. HCRU and costs of care were reported for the year preindex (baseline) and at 1- and 2-year follow-ups. Results: We identified 1841 patients with oHCM (63 ± 15 years; 52% male). The mean number of hypertrophic cardiomyopathy (HCM)-related outpatient and cardiology visits increased from baseline to 1-year follow-up (2.3 vs. 7.8 and 0.6 vs. 2.2, respectively). At baseline, 8% of patients had ≥1 HCM-related inpatient hospitalization (mean 0.11 visits, 5.4 days length of stay), increasing to 27% postdiagnosis (mean 0.42 visits, 5.9 days length of stay). Total HCM-related costs increased from $5968 to $20,290 at 1-year follow-up, largely driven by inpatient hospitalization costs ($3889 vs. $14,369) and surgical costs ($2259 vs. $7217). The proportion with ≥1 HCM-related prescription increased from baseline (69%; mean fills 5.3) to 1-year follow-up (82%; mean fills 7.8). Pharmacy costs were generally low but also increased ($449 vs. $752). Conclusions: This benchmark economic dataset for management and evaluation of patients with oHCM shows increased HCM-related costs over a 2-year period after oHCM diagnosis, driven by inpatient hospitalizations and surgical costs. Medication use was high, but costs were low, possibly reflecting use of generic multi-indication drugs for oHCM treatment.

Clinical Diagnosis of Hypertrophic Cardiomyopathy Over Time in the United States (A Population-Based Claims Analysis).

Hypertrophic cardiomyopathy (HC) is a common genetic heart disease. However, the number of gene mutation carriers who develop HC and manifest clinical symptoms is not well established. Our objective was to estimate annual prevalence and incidence rates of clinically diagnosed HC in the United States. Data from the HealthCore Integrated Research Database (HIRD) were interrogated for years 2013-2019 to identify patients with ≥1 claim of HC International Classification of Diseases, Clinical Modification Ninth and Tenth Revision diagnosis codes. In 2013, among 16,243,109 patients, 8,526 were identified with HC, yielding an estimated prevalence of clinically diagnosed HC of 0.052% (0.035% for obstructive [oHC], 0.017% for nonobstructive [nHC]). This prevalence yielded an estimated 164,403 patients with clinical diagnosis of HC. For the same year, the incidence of new HC diagnoses was 0.030% (0.020% for oHC, 0.010% for nHC). Over the following 6 years, prevalence and incidence of HC increased by 0.005%/year (p <0.01) and 0.001%/year (p <0.01), respectively, with an estimated 262,591 patients with a clinical diagnosis of HC in 2019. Over this period, incidence of nHC increased (0.012% vs 0.026%, p <0.01), whereas incidence of oHC decreased (0.020% versus 0.015%, p <0.01). In conclusion, over 6 years, the number of patients with clinically diagnosed HC in the United States increased 1.5-fold to ∼262,591, primarily because of a rise in nHC diagnoses. These prevalence data support further investigation to better understand factors accounting for increasing clinical recognition of HC.

Characteristics and Outcomes of Patients With Heart Failure With Reduced Ejection Fraction After a Recent Worsening Heart Failure Event.

Background Contemporary trials of patients with heart failure with reduced ejection fraction (HFrEF) required a recent worsening heart failure (WHF) event for inclusion. We aimed to describe characteristics and outcomes of patients with HFrEF and a recent WHF event at a large tertiary referral center. Methods and Results We identified adult patients with chronic symptomatic HFrEF (ejection fraction ≤35%) treated at Duke University between January 1, 2009, and December 31, 2018, and applied a set of exclusion criteria to generate a cohort similar to those enrolled in contemporary heart failure trials. Patients were stratified by presence or absence of a recent WHF event, defined as an emergency department visit for heart failure or hospitalization for heart failure in the prior 12 months. Characteristics and outcomes including death and hospitalization were assessed. Of 3867 patients with HFrEF meeting study criteria, 2823 (73.0%) had a WHF event in the prior 12 months. Compared with patients without a WHF event, those with a WHF event were more likely to be under-represented racial and ethnic groups and had lower ejection fraction, a greater burden of comorbidities, and more echocardiographic evidence of cardiac dysfunction. Despite higher use of guideline-directed therapies, patients with a WHF event had higher rates of death (hazard ratio, 2.30; 95% CI, 2.01-2.63), all-cause hospitalization (hazard ratio, 1.56; 95% CI, 1.42-1.71), and heart failure hospitalization (hazard ratio, 1.59; 95% CI, 1.44-1.75) through 5 years compared with those without a recent WHF event. Conclusions WHF events are common in patients with HFrEF and are associated with more advanced disease. Patients with recent WHF have high rates of death and hospitalization, underscoring the need for novel therapies in this large subgroup of patients with HFrEF.

Economic Evaluation of Linaclotide for the Treatment of Adult Patients With Chronic Idiopathic Constipation in the United States.

PURPOSE: To evaluate the effectiveness and costs of linaclotide (Linzess) versus lubiprostone (Amitiza) in the treatment of adult patients with chronic idiopathic constipation (CIC). DESIGN: A decision-tree model using model inputs derived from published literature, linaclotide phase 3 trial data, and a physician survey. METHODOLOGY: Measures of treatment efficacy were selected based on comparability between trial data, with posthoc analyses of linaclotide required to ensure comparability with available lubiprostone data. Response to therapy was defined as (1) having one of the best two satisfaction answers of a 5-point global treatment satisfaction scale at Week 4 or (2) having a weekly spontaneous bowel movement (SBM) frequency 4 at Week 4. Patients who do not respond to therapy are assumed to accrue costs associated with a treatment failure. Model time horizon is aligned with the lubiprostone clinical trial duration of 4 weeks. Model outputs include response rates, quality-adjusted life-years (QALYs) and direct costs. RESULTS: Linaclotide was associated with lower per-patient costs vs lubiprostone for both definitions of response ($946 vs $1,015 for global assessment and $727 vs $737 for SBM frequency). When treatment response was based on a global assessment of treatment satisfaction, linaclotide was associated with higher effectiveness (response: 39.3% vs 35.0%). For SBM frequency, linaclotide was slightly less effective compared to lubiprostone (response: 58.6% vs 59.6%), but also less costly. Base-case results were robust in sensitivity analysis. CONCLUSIONS: Linaclotide is less expensive with similar effectiveness when compared to lubiprostone for the treatment of CIC in adult patients.

Economic evaluation of linaclotide for the treatment of adult patients with irritable bowel syndrome with constipation in the United States.

OBJECTIVES: To use techniques of decision-analytic modeling to evaluate the effectiveness and costs of linaclotide vs lubiprostone in the treatment of adult patients with irritable bowel syndrome with constipation (IBS-C). METHODS: Using model inputs derived from published literature, linaclotide Phase III trial data and a physician survey, a decision-tree model was constructed. Response to therapy was defined as (1) a ≥ 14-point increase from baseline in IBS-Quality-of-Life (IBS-QoL) questionnaire overall score at week 12 or (2) one of the top two responses (moderately/significantly relieved) on a 7-point IBS symptom relief question in ≥ 2 of 3 months. Patients who do not respond to therapy are assumed to fail therapy and accrue costs associated with a treatment failure. Model time horizon is aligned with clinical trial duration of 12 weeks. Model outputs include number of responders, quality-adjusted life-years (QALYs), and total costs (including direct and indirect). Both one-way and probabilistic sensitivity analyses were conducted. RESULTS: Treatment for IBS-C with linaclotide produced more responders than lubiprostone for both response definitions (19.3% vs 13.0% and 61.8% vs 57.2% for IBS-QoL and symptom relief, respectively), lower per-patient costs ($803 vs $911 and $977 vs $1056), and higher QALYs (0.1921 vs 0.1917 and 0.1909 vs 0.1894) over the 12-week time horizon. Results were similar for most one-way sensitivity analyses. In probabilistic sensitivity analyses, the majority of simulations resulted in linaclotide having higher treatment response rates and lower per-patient costs. LIMITATIONS: There are no available head-to-head trials that compare linaclotide with lubiprostone; therefore, placebo-adjusted estimates of relative efficacy were derived for model inputs. The time horizon for this model is relatively short, as it was limited to the duration of available clinical trial data. CONCLUSIONS: Linaclotide was found to be a less costly option vs lubiprostone for the treatment of adult patients with IBS-C.

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.