Early Use of Biologics Reduces Healthcare Costs in Crohn's Disease: Results from a United States Population-Based Cohort.

BACKGROUND: Early initiation of biologics in moderate-to-severe Crohn's disease (CD) may significantly alter disease progression, resulting in better patient outcomes. Limited real-world data exist on the impact of early biologic use in patients with CD in the United States. AIMS: We aimed to characterize biologic initiation and subsequent healthcare resource utilization (HCRU) in adults with recently diagnosed CD. METHODS: Patients with CD who initiated biologic treatment within 2 years of diagnosis (index date) were identified from medical and pharmacy claims (Merative L.P. MarketScan Database from 2010 to 2016) and classified as early (≤ 12 months post-index) or late (> 12-24 months post-index) biologic initiators. Propensity score matching balanced patient characteristics up to 1 year post-index. Differences in HCRU frequency and costs 1-2 years post-index were compared between the matched groups. RESULTS: After propensity score matching, 672 pairs of early and late biologic initiators were identified. Patients who initiated biologics early had fewer outpatient visits (15.5 vs 19.8, 95% confidence interval [CI] for difference: 2.7, 6.1) and lower total medical costs ($13,646.20 vs $22,180.70, 95% CI for difference: 4748.9, 12,320.1) 1-2 years post-index than late biologic initiators. Early biologic initiators had higher medication costs 1-2 years post-index ($33,766.30 vs $30,580.70, 95% CI: 546.1, 5825.1) but lower combined medical and medication costs ($47,412.50 vs $52,761.50, 95% CI: 801.5, 9896.40). CONCLUSIONS: While biologic treatments are costly, patients initiating biologics sooner after diagnosis appear to have better HCRU outcomes and require fewer healthcare resources at 1-2 years post-index, potentially leading to overall cost savings.

Clinical Characteristics and Treatment Patterns Among Patients Diagnosed With Cluster Headache in U.S. Healthcare Claims Data.

OBJECTIVE: To characterize demographics, clinical characteristics, and treatment patterns of patients with cluster headache (CH). BACKGROUND: CH is an uncommon trigeminal autonomic cephalalgia with limited evidence-based treatment options. Patients suffer from extremely painful unilateral headache attacks and autonomic symptoms with episodic and chronic cycles. DESIGN/METHODS: This retrospective analysis used insurance claims from Truven Health Analytics MarketScan® research databases from 2009 to 2014. Two cohorts were compared: CH patients (with ≥2 CH claims) were propensity score matched with 4 non-headache controls, all with continuous enrollment for 12 months before and after the date of first CH claim or matched period among controls. RESULTS: CH patients (N = 7589) were mainly male (57.4%) and 35-64 years old (73.2%), with significantly more claims for comorbid conditions vs controls (N = 30,341), including depressive disorders (19.8% vs 10.0%), sleep disturbances (19.7% vs 9.1%), anxiety disorders (19.2% vs 8.7%), and tobacco use disorders (12.8% vs 5.3%), with 2.5 times greater odds of suicidal ideation (all P < .0001). Odds of drug dependence were 3-fold greater among CH patients (OR = 2.8 [95% CI 2.3-3.4, P < .0001]). CH patients reported significantly greater use of prescription medications compared with controls; 25% of CH patients had >12 unique prescription drug claims. Most commonly prescribed drug classes for CH patients included: opiate agonists (41%), corticosteroids (34%), 5HT-1 agonists (32%), antidepressants (31%), NSAIDs (29%), anticonvulsants (28%), calcium antagonists (27%), and benzodiazepines (22%). Only 30.4% of CH patients received recognized CH treatments without opioids during the 12-month post-index period. These patients were less likely to visit emergency departments or need hospitalizations (26.8%) as compared to CH patients with no pharmacy claims for recognized CH treatments or opioids (33.6%; P < .0001). CONCLUSIONS: The burden of CH is associated with significant co-morbidity, including substance use disorders and suicidal ideation, and treatment patterns indicating low use of recognized CH treatments.

Treatment patterns in paediatric and adult patients with SLE: a retrospective claims database study in the USA.

OBJECTIVE: To assess real-world treatment regimens and patterns in childhood-onset SLE (cSLE) and adult-onset SLE (aSLE) cohorts, including similarities in treatments, duration of use and adherence. METHODS: This retrospective study utilised data from Merative L.P. MarketScan Research Databases (USA). Index date was the date of first SLE diagnosis (2010-2019). Patients aged <18 years (cSLE) and ≥18 years (aSLE) at index date with confirmed SLE diagnosis and ≥12 months continuous enrolment during pre-index and post-index periods were included. The cohorts were stratified based on the presence (existing) or absence (new) of pre-index SLE. Primary outcomes (post-index period) included treatment regimens (all patients), and adherence (proportion of days covered (PDC)) and discontinuation of therapies initiated within 90 days of diagnosis (new patients). Univariate comparisons between cSLE and aSLE cohorts were performed using Wilcoxon rank-sum and χ2 (or Fisher's exact) tests. RESULTS: cSLE cohort included 1275 patients (mean age=14.1 years) and aSLE cohort included 66 326 patients (mean age=49.7 years). Antimalarials and glucocorticoids were commonly used among new (cSLE=64.4%/62.0%; aSLE=51.8%/49.7%) and existing (cSLE=68.6%/58.9%; aSLE=63.8%/51.3%) patients in both cohorts. Median oral glucocorticoid dose (prednisone equivalent) was higher in cSLE vs aSLE (new=22.1 vs 14.0 mg/day; existing=14.4 vs 12.3 mg/day; p<0.05). Mycophenolate mofetil use was higher in patients with cSLE vs aSLE (new=26.2% vs 5.8%; existing=37.6% vs 11.0%; p<0.0001). Compared with aSLE, more patients used combination therapies in cSLE (p<0.0001). Median PDC was higher in cSLE vs aSLE for antimalarials (0.9 vs 0.8; p<0.0001) and oral glucocorticoids (0.6 vs 0.3; p<0.0001). Treatment discontinuation was lower in cSLE vs aSLE for antimalarials (25.0% vs 33.1%; p<0.0001) and oral glucocorticoids (56.6% vs 71.2%; p<0.0001). CONCLUSIONS: Management of cSLE and aSLE includes the same medication classes; differences include more intensive use of therapy in cSLE, warranting the need for approved safe medications for cSLE.

Real-World Biologic Adherence, Persistence, and Monotherapy Comparisons in US Patients with Psoriasis: Results from IBM MarketScan® Databases.

INTRODUCTION: Limited real-world data are available comparing multiple biologics on their adherence, persistence, and the use of concomitant biologics in the treatment of moderate-to-severe psoriasis in clinical practice. The objective was to compare persistence of and adherence to ixekizumab (IXE) treatment, as monotherapy or with concomitant medication, versus patients receiving other commonly prescribed biologics. METHODS: Patients who newly initiated IXE, adalimumab (ADA), etanercept (ETN), secukinumab (SEC), or ustekinumab (UST) in IBM MarketScan® databases with diagnosis of psoriasis were identified. Treatment comparisons on medication persistence, adherence, and monotherapy were based on balanced samples after inverse probability of treatment weighting (IPTW). RESULTS: A higher proportion of patients receiving IXE had had previous biologic therapies (50.3%) versus other biologics (ADA: 9.1%, ETN: 10.9%, SEC: 33.9%, UST: 19.7%). Patients treated with IXE showed statistically (p < 0.001) greater persistence than patients treated with SEC, ADA, UST, or ETN at both 1-year follow-up and up to 3 years of follow-up. Adherence for patients treated with IXE was significantly (p < 0.001) higher compared to ADA, ETN, and UST at both 1-year follow-up and up to 3 years of follow-up. There was no significantly higher adherence in patients treated with IXE compared to those treated with SEC at 1-year follow-up, but IXE had higher adherence than SEC (p < 0.05) at 1-3 year follow-up. IXE showed longer time on monotherapy than ADA (p < 0.001), ETN (p < 0.001), SEC (p < 0.05), and UST (p < 0.001) for both 1-year and 1-3 year follow-up. Sensitivity analyses on persistence, adherence, and monotherapy with further model adjustments after IPTW confirmed the findings. CONCLUSIONS: Patients treated with IXE were more persistent on and adherent to treatment and remained on monotherapy longer compared to those on all other commonly prescribed biologics combined or with individual biologics.

Development of a claims-based flare algorithm for systemic lupus erythematosus.

OBJECTIVE: To develop a claims-based algorithm identifying systemic lupus erythematosus (SLE) flares using a linked claims-electronic medical record (EMR) dataset. METHODS: This study was a retrospective analysis of linked administrative claims and EMR data spanning 1 January 2003 to 31 March 2019. Included were adult SLE patients with at least 12 months of continuous enrollment in claims data, 12 months of clinical activity in EMR, and an absence of malignancies excluding basal and squamous cell carcinoma. Patient follow-up was divided into 30-day windows, and a proxy SLEDAI-2K score based on the EMR data was calculated for each 30-day period. A flare was defined as an increase of at least 4 from the baseline score. A series of potential flare predictor variables identified in claims were based on a combination of established variables from a previous algorithm, with the addition of other SLE-related indicators based on clinical input. Logistic regression models were built to predict monthly SLE flares. RESULTS: Inclusion criteria identified 2427 patients. Results from a logistic model with forward selection capping the number of variables at 10 performed well with a c-statistic of 0.76 and a Brier score of 0.07. The top five predictors were any inpatient admission (OR = 4.76), outpatient office visit (OR = 3.04), MRI (OR = 2.26), ER visit (OR = 2.25), and number of rheumatology visits (OR = 1.75); p < .01 for all. CONCLUSIONS: The final algorithm shows promise in providing an alternative and more streamlined way for identifying likely flares in administrative claims data that will advance the study of SLE within the context of flares.

Comparative Effectiveness of Dexamethasone in Hospitalized COVID-19 Patients in the United States.

INTRODUCTION: To compare the mortality of hospitalized patients with COVID-19 between those that required supplemental oxygen and received dexamethasone with a comparable set of patients who did not receive dexamethasone. METHODS: We utilized the Premier Health Database to identify hospitalized adult patients with COVID-19 from July 1, 2020-January 31, 2021. Index date was when patients first initiated oxygen therapy. The primary endpoint was in-hospital mortality for patients receiving dexamethasone versus those not receiving dexamethasone 1-day pre- to 1-day post-index period. Secondary endpoints included 28-day mortality, time to in-hospital mortality, progression to invasive mechanical ventilation or death, time to discharge, and proportion discharged alive by day 28. Twenty-three models using weighting, matching, stratification, and regression were deployed through the concept of frequentist model average (FMA) to estimate the effect of dexamethasone on all-cause mortality up to the 28-day hospitalization period. RESULTS: A total of 1,208,881 patients with COVID-19 were screened; as an inpatient 255,216 used oxygen, and 251,536 were included in the analysis. In the dexamethasone group, odds of in-hospital mortality were higher than those of the comparator (FMA: odds ratio [OR] 1.15, 95% CI 1.08, 1.22). Using a best fit model, OR for in-hospital mortality was non-significant for the dexamethasone group compared with the comparator (OR 1.02, 95% CI 0.92, 1.14). Dexamethasone treatment was associated with poorer outcomes versus the comparator group across the majority of secondary endpoints, except for number of days in hospital, which was lower in the dexamethasone group versus the comparator group (mean difference - 2.14, 95% CI - 2.43, - 1.47). CONCLUSIONS: Hospitalized adult patients with COVID-19 who required supplemental oxygen and received dexamethasone did not have a survival benefit versus similar patients not receiving dexamethasone. The dexamethasone group was not associated with favorable responses for outcomes such as progression to death or mechanical ventilation and time to in-hospital death.

Frequency of Prescription Claims for Drugs that May Interact with Janus Kinase Inhibitors Among Patients with Rheumatoid Arthritis in the US.

INTRODUCTION: This study describes the frequency of prescription claims for drugs that may interact with Janus kinase (JAK) inhibitors among adult patients with rheumatoid arthritis (RA) in a large US claims database. METHODS: This observational, retrospective, cross-sectional study of the IBM® MarketScan® Research Commercial and the Medicare Supplemental Database included adults (≥ 18 years) with ≥ 2 outpatient claims 30 or more days apart or ≥ 1 inpatient visit claim with an RA diagnosis between January 1, 2013 and March 31, 2017 (the index period). During the study period, from January 1, 2013 to March 31, 2018, strong organic anion transporter (OAT3) inhibitors, strong cytochrome P450 (CYP) 3A4 inhibitors, and moderate or strong CYP3A4 inhibitors in combination with strong CYP2C19 inhibitors, were identified as drugs with potential for drug-drug interactions (DDIs) with JAK inhibitors approved for RA treatment in the US. Descriptive statistics were conducted. RESULTS: A total of 152,853 patients met eligibility criteria. Approximately 76% were women and the median age was 57 years. Of these patients, < 0.1% had a claim for a strong OAT3 inhibitor, and 1% had claims for the combination of a strong CYP3A4 and strong CYP2C19 inhibitor; 3% of patients had a claim for a strong CYP3A4 inhibitor and almost 10% had claims for both a moderate CYP3A4 and a strong CYP2C19 inhibitor. CONCLUSIONS: Up to 10% of RA patients have been prescribed a drug with a potential JAK interaction. Rheumatologists should consider potential DDIs when managing patients with RA.

Inpatient Hospital Costs for COVID-19 Patients in the United States.

INTRODUCTION: Reliable cost and resource use data for COVID-19 hospitalizations are crucial to better inform local healthcare resource decisions; however, available data are limited and vary significantly. METHODS: COVID-19 hospital admissions data from the Premier Healthcare Database were evaluated to estimate hospital costs, length of stay (LOS), and discharge status. Adult COVID-19 patients (ICD-10-CM: U07.1) hospitalized in the US from April 1 to December 31, 2020, were identified. Analyses were stratified by patient and hospital characteristics, levels of care during hospitalization, and discharge status. Factors associated with changes in costs, LOS, and discharge status were estimated using regression analyses. Monthly trends in costs, LOS, and discharge status were examined. RESULTS: Of the 247,590 hospitalized COVID-19 patients, 49% were women, 76% were aged ≥ 50, and 36% were admitted to intensive care units (ICU). Overall median hospital LOS, cost, and cost/day were 6 days, US$11,267, and $1772, respectively; overall median ICU LOS, cost, and cost/day were 5 days, $13,443, and $2902, respectively. Patients requiring mechanical ventilation had the highest hospital and ICU median costs ($47,454 and $41,510) and LOS (16 and 11 days), respectively. Overall, 14% of patients died in hospital and 52% were discharged home. Older age, Black and Caucasian race, hypertension and obesity, treatment with extracorporeal membrane oxygenation, and discharge to long-term care facilities were major drivers of costs, LOS, and risk of death. Admissions in December had significantly lower median hospital and ICU costs and LOS compared to April. CONCLUSION: The burden from COVID-19 in terms of hospital and ICU costs and LOS has been substantial, though significant decreases in cost and LOS and increases in the share of hospital discharges to home were observed from April to December 2020. These estimates will be useful for inputs to economic models, disease burden forecasts, and local healthcare resource planning.

Validation of claims-based indicators used to identify flare-ups in inflammatory bowel disease.

BACKGROUND & AIMS: There are currently no validated claims-based indicators for identifying a worsening of disease in patients with inflammatory bowel disease (IBD). Therefore, we aimed to develop and validate indicators that identify flare-ups of IBD using data from Danish nationwide registries. METHODS: Using Danish nationwide administrative data, we identified all patients with Crohn's disease (CD) or ulcerative colitis (UC) who had at least one measurement of faecal calprotectin between 1 January 2015 and 31 June 2017. We tested several different claims-based indicators of disease flare-ups against levels of faecal (F-)calprotectin (no flare-up: <250 mg/kg; mild flare-up: 250-1000 mg/kg; severe flare-up: ⩾1000 mg/kg). A generalised estimating equation was used to evaluate whether the proposed indicators could predict disease activity. RESULTS: A total of 890 children and 4719 adults with CD, and 592 children and 5467 adults with UC were included in the study. During the observation period, 48-61% and 48-55% of the CD and UC patients, respectively, had no flare-up, 26-29% (CD) and 24-26% (UC) experienced a mild flare-up, and 12-23% (CD) and 21-27% (UC) experienced a severe flare-up. Combinations of indicators that could predict a flare-up in CD and UC adults included hospitalisation, surgery, initiation or switch of biological therapy, treatment with systemic steroids, locally acting steroids or topical 5-aminosalicylates, colonoscopy/sigmoidoscopy, and magnetic resonance imaging/computed tomography. In children, only the number of gastroenterology visits was significant as an indicator among UC patients, and none were seen in children with CD. Overall, the indicator combinations resulted in a predictive ability of 0.62-0.67. CONCLUSION: Administrative claims data can be useful for identifying patients exhibiting (F-calprotectin defined) flare-ups of their IBD. Clinically relevant events captured in the Danish national patient registry are associated with increased levels of calprotectin and hence increased disease activity, and can be used as valid outcomes in future studies.

Health Care Utilization and Direct Costs Among Patients Diagnosed with Cluster Headache in U.S. Health Care Claims Data.

BACKGROUND: Cluster headache (CH) is a rare trigeminal cephalalgia that is associated with extremely painful unilateral headache attacks and autonomic symptoms. Attacks may be episodic or chronic and associated with substantial suffering due to excruciating pain and limited treatment options. Frequent cluster headaches cause substantial burden for patients, resulting in reduced productivity caused by disability, as well as direct costs in some European countries. Less is known, however, about direct costs of recurring health care resource utilization (HCRU) in the United States. OBJECTIVE: To characterize HCRU and direct costs associated with CH in the United States from a third-party payer perspective. METHODS: This retrospective observational study analyzed claims data from the Truven Health Analytics MarketScan Research Databases from 2009-2014. Two cohorts were compared: CH (> 2 diagnostic CH claims) and controls (nonheadache patients). All patients were enrolled continuously for ± 12 months from date of first CH claim. HCRU and direct costs were examined during 12 months post-index as all-cause and CH-specific. Cost and HCRU differences were compared using propensity score-adjusted bin bootstrapping. RESULTS: CH and control cohorts comprised 6,562 and 143,761 patients (aged ≥ 18 years), respectively. Post-index, 36.9% of CH patients versus 16.2% of controls were admitted to the emergency department (ED), and 14.8% versus 6.1% were hospitalized for any reason, respectively (each P < 0.001). CH patients had a 2- to 3-fold significantly greater number of all-cause mean claims for outpatient visits (26.5 vs. 12.4 visits), hospital visits (0.2 vs. 0.1 visits), and ED visits (1.0 vs. 0.3 visits) versus controls (all P < 0.001). The mean number of all-cause visits with reported radiology and laboratory claims was 1.5- to 2.0-fold greater in CH patients versus controls (each P < 0.001). Mean total direct costs for all-cause claims were more than 2-fold greater in post-index ($16,530) for CH patients versus controls ($7,197, P < 0.0001). Similarly, mean direct all-cause costs attributable to outpatient, inpatient, and pharmacy claims were significantly (2-fold) greater; radiology and ED claims were 3- to 4-fold greater among CH patients versus controls (all P < 0.001). However, CH was cited infrequently as a reason for HCRU, indicating that comorbid conditions may substantially increase HCRU in CH patients. The most common reasons for ED admission in CH patients were gastric ulcer with hemorrhage, sub-arachnoid hemorrhage, and headache symptoms. The most common hospital discharge diagnoses for CH patients not observed in top 10 reasons in controls included cerebral artery occlusion/unspecified with cerebral infarction, headache symptoms, syncope/collapse, and diverticulitis. CONCLUSIONS: These findings suggest that, from a payer perspective, CH patients incur significantly higher health care costs versus controls. However, these high costs were not exclusively headache-related. Extrapolating our cost findings to estimated U.S. prevalence rates, approximate total direct cost for CH is greater than $2.8 billion/year. DISCLOSURES: Eli Lilly and Company was the sole sponsor and funder for this study and was responsible for the study design, data collection, data analysis, interpretation of data, and decision to publish the findings. All authors are employees and minor stockholders of Eli Lilly and Company.