Durability of Near-Complete Skin Clearance in Patients with Psoriasis Using Systemic Biologic Therapies: Real-World Evidence from the CorEvitas Psoriasis Registry.

INTRODUCTION: Near-complete skin clearance has become a rapidly achievable treatment goal for patients with psoriasis receiving systemic biologic therapies. However, real-world evidence for durability of near-complete skin clearance and risk factors associated with loss of near-complete skin clearance is limited. METHODS: This study described durability of near-complete skin clearance (≥ 90% improvement in Psoriasis Area and Severity Index from initiation; PASI90) and identified clinical factors or patient characteristics associated with loss of PASI90 among patients with psoriasis from the CorEvitas Psoriasis Registry (April 2015-August 2021). Included patients had PASI > 5 at biologic initiation and achieved PASI90 at approximately 6 months from initiation (index). A Kaplan-Meier estimate described time to loss of treatment response over 24 months follow-up from index. Proportional hazards regression was used to identify independent predictors of loss of treatment response. RESULTS: This study included 687 patient initiations (instances of patients initiating a biologic). Following achievement of PASI90, treatment response was maintained in more than half of patient initiations (54%). Treatment response was maintained at 6, 12, and 18 months from index in an estimated 73% (95% [confidence interval] CI 70-77%), 60% (95% CI 56-63%), and 50% (95% CI 47-54%) of patient initiations, respectively. Adjusted hazards regression suggested non-White race, full-time employment, greater body weight, concomitant psoriatic arthritis, prior use of biologics, and clinically meaningful skin symptoms were associated with loss of treatment response. CONCLUSIONS: Among real-world patients with psoriasis who achieved PASI90 with biologic therapy, about one-quarter lost response at 6 months, and half lost response at 18 months. Prior use of a biologic therapy and clinically meaningful skin symptoms at index, including itch and skin pain, were associated with loss of treatment response. Therefore, dermatologists may consider focusing on patient-reported symptoms as part of any intervention designed to reduce the likelihood of loss of response to biologic therapies. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02707341.

Many people with psoriasis are treated with biologic medications that work to improve symptoms associated with psoriasis, including inflammation. These medications can lead to almost clear skin for many people. However, there is limited information available about how long almost clear skin can be maintained with biologic medications, and what predicts who is likely to lose it. To explore these questions, we examined a database of patients with psoriasis (the CorEvitas Psoriasis Registry) that records how clear patients' skin is and the medications they take. Out of every 100 patients, 54 maintained almost clear skin and stayed on their original medication for 2 years after first having almost clear skin. Out of every 100 patients, 73, 60, and 50 maintained almost clear skin and remained on their original medication at 6, 12, and 18 months after they had achieved this response. The results indicated that patients who were not White, worked full time, previously used a biologic medication, or had itchy and/or painful skin after they had achieved almost-clear skin were more likely to change their medication and/or no longer have almost-clear skin. These results suggest that dermatologists may consider focusing on patient-reported characteristics when deciding how to treat their patients, to reduce the likelihood that they lose their response to the medication they are prescribed.

Skin Clearance is Associated with Reduced Treatment Failure in Patients with Psoriasis: Real-World Evidence from the CorEvitas Psoriasis Registry.

INTRODUCTION: Complete and near-complete skin clearance have become achievable treatment goals for patients with psoriasis receiving systemic biologic therapies. However, there is limited real-world evidence regarding the impact of the degree of skin clearance on biologic treatment patterns among these patients. METHODS: This longitudinal cohort study assessed the relationship between degree of skin clearance following initiation of a systemic biologic therapy and treatment failure among patients from the CorEvitas Psoriasis Registry (April 2015-August 2021). Patients had Psoriasis Area and Severity Index (PASI) score > 5 at systemic biologic therapy initiation and ≥ 1 follow-up visit(s) within 15 months of initiation. Treatment failure (discontinuation due to poor response/adverse event; addition of non-biologic therapy) and degree of skin clearance (measured by PASI) were assessed following biologic initiation. Proportional hazards regression was used to estimate the association between PASI response level and treatment failure over follow-up. RESULTS: This study included 2701 patient initiations from 2516 unique patients with 3846 total visits over follow-up. Over half of the patient initiations (n = 1412; 52.3%) were among patients with PASI >10. Treatment failure occurred in 1.3% of visits at which PASI100 was achieved, while those achieving PASI90 - < 100 and PASI75 - < 90 had treatment failure rates of 3.4% and 3.5%, respectively. After adjustment for confounders, the risk of treatment failure was two to three times higher in the PASI90 - < 100 (hazard ratio [HR] = 2.61; 95% confidence interval [CI] 1.35, 5.02; p = 0.004) and PASI75 < 90 (HR = 2.97; CI 1.58, 5.58; p = 0.001) groups compared to the PASI100 group. The risk of treatment failure was more than 20 times higher in the < PASI75 group versus the PASI100 group (HR = 22.26; CI 13.32, 37.21; p < 0.001). CONCLUSIONS: The results suggest that patients are more likely to remain on a systemic biologic therapy if they achieve near-complete or complete skin clearance, supporting the continued need to target skin clearance as a treatment goal in psoriasis. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02707341.

Many people with psoriasis are often treated with biologic medications that work to improve symptoms associated with psoriasis, including inflammation. These medications can lead to clear or almost-clear skin for many people. However, there is limited information available about how achieving this goal affects whether patients continue taking their biologic medication or add a new non-biologic medication. The data source for this study was a database of patients with psoriasis (the CorEvitas Psoriasis Registry) that records how clear patients' skin is and what medications they take. Over 1 year after starting a biologic medication, approximately 1 out of every 100 patients that achieved clear skin after taking a biologic medication stopped using that medication, and approximately 3 out of every 100 patients with almost-clear skin after taking a biologic medication stopped using that medication. Meanwhile, around 20 out of every 100 patients that did not have clear or almost-clear skin after taking a biologic medication stopped using that medication. Furthermore, patients who did not have clear or almost-clear skin after taking a biologic medication had more than 20 times greater risk of stopping their medication than those who did have clear or almost-clear skin after taking a biologic medication. These results suggest that patients are more likely to remain on their biologic medication if they experience clear or almost-clear skin after taking a biologic medication and that patients and their providers should aim for this goal when taking a biologic medication.

Treatment Patterns and Healthcare Resource Utilization Among Newly Diagnosed Psoriasis, Psoriatic Arthritis, Axial Spondyloarthritis, and Hidradenitis Suppurativa Patients with Past Diagnosis of an Inflammatory Condition: A Retrospective Cohort Analysis of Claims Data in the United States.

INTRODUCTION: Psoriasis (PSO), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), and hidradenitis suppurativa (HS) are chronic inflammatory diseases (CIDs) often diagnosed and treated individually. However, genetic overlaps exist among CIDs, and patients with one are at risk of developing others within the same spectrum. This analysis characterized treatment patterns along with clinical and economic burdens of newly diagnosed CIDs among patients with an additional past diagnosis of PSO, PsA, axSpA, or HS. METHODS: This study used MarketScan® databases to examine demographics, treatment patterns, and healthcare resource utilization for patients with ≥ 1 claim for PSO or HS or ≥ 2 claims for PsA or axSpA, and continuous enrollment in the year before (baseline period) and following (follow-up period) the date of first diagnosis (incident diagnosis). Comorbidities and new CID diagnoses with a past diagnosis of PSO, PsA, axSpA, or HS, were examined. RESULTS: The analysis included 298,794 patients (maximum of 1202 patients with ≥ 1 incident diagnoses): 134,233 had incident PSO; 9914 had incident PsA; 115,194 had incident axSpA; and 40,655 had incident HS. Prevalence of ≥ 1 CID diagnosis among patients with past diagnosis of PSO, PsA, axSpA, or HS was 4959/134,233 (3.7%), 5256/9914 (53.0%), 3205/115,194 (2.8%), and 1180/40,655 (2.9%), respectively. In patients with incident axSpA and past PsA diagnosis, incident axSpA and past HS diagnosis, and incident HS and past PSO diagnosis, steroid and opioid use were high across baseline and follow-up periods and use of biologic disease-modifying antirheumatic drugs increased from baseline to follow-up. Disease-related costs increased absolutely and increased or remained high as a proportion of all-cause costs. CONCLUSION: Patients with newly diagnosed CIDs and additional past diagnosis of PSO, PsA, axSpA, or HS experienced high treatment utilization and healthcare costs. These findings highlight the need for payers, health technology assessment agencies, clinicians, and other stakeholders to explore the co-management of CIDs, rather than treating them separately.

Epidemiology and injectable antiseizure medication treatment patterns of seizure patients treated in United States hospitals.

Objective: This study aimed to examine the epidemiology of seizures, clinical outcomes, and antiseizure medication treatment patterns among seizure patients treated in United States hospitals. Design: A retrospective cross-sectional study was conducted using data from a large geographically diverse hospital discharge database. Setting: 860 acute care hospitals in the United States. Participants: Patients aged ≥18 years with an outpatient emergency department or inpatient visit between 1 July 2016-31 December 2019 were included. Intervention: None. Main outcomes and measures: Key outcomes included prevalence of seizure, seizure type, admission point of origin, intensive care unit admission, discharge status, and injectable antiseizure medication utilization. Seizures were identified by the International Classification of Disease, Tenth Revision, Clinical Modification diagnosis codes. Results: Among 36,598,627 unique emergency department outpatients (72,372,464 outpatient visits) and 16,543,592 unique inpatients (24,923,489 inpatient admissions) analyzed, seizure was present in 2.1% of outpatients (1.87% of outpatient visits) and 4.9% of inpatients (4.8% of inpatient admissions). In overall seizure patients, 49.1% were unclassified, 4.4% had generalized onset, 2.9% had focal onset, and 42.8% were categorized as other (including 38.5% with convulsion). Among seizure-associated inpatient admissions, <1% were transferred directly from skilled nursing facility or other long-term care facilities but 22.7% were discharged to such facilities. Nearly a third (31%) of all inpatients were admitted to ICU. About 88.3% of patients with injectable ASM use had monotherapy, 4.6% had polytherapy with 1 day or multiple non-consecutive days of overlap, and 7.0% had polytherapy with ≥2 consecutive days of overlap. The percentage of patients with no step down to any oral ASM ranged between 34.0-57.0%. Conclusions: Seizures affect a substantial number of hospital-based emergency department outpatient and inpatient encounters and are associated with poor clinical outcomes and significant healthcare burden. Concomitant use of injectable ASMs is uncommon and a high percentage of IV ASM users with a diagnosis of seizure had no step down to oral therapy. Relevance: The study findings may inform clinicians and hospital decision makers about current clinical practice and burden of seizures and identify areas to improve overall outcomes for patients with seizures.

Clinical and Economic Outcomes of Intravenous Brivaracetam Compared With Levetiracetam for the Treatment of Seizures in United States Hospitals.

Background: Seizures are common among hospitalized patients. Levetiracetam (LEV), a synaptic vesicle protein 2A (SV2A) ligand, is a common intravenous (IV) anti-seizure medication option in hospitals. Brivaracetam (BRV), a selective SV2A ligand for treatment of focal seizures in patients ≥16 years, has greater binding affinity, higher lipophilicity, and faster brain entry than IV LEV. Differences in clinical outcomes and associated costs between IV BRV and IV LEV in treating hospitalized patients with seizure remain unknown. Objectives: To compare the clinical outcomes, costs, and healthcare resource utilization between patients with seizure treated with IV BRV and those with IV LEV within hospital setting. Design/Methods: A retrospective cohort analysis was performed using chargemaster data from 210 United States hospitals in Premier Healthcare Database. Adult patients (age ≥18 years) treated intravenously with LEV or BRV (with or without BZD) and a seizure discharge diagnosis between July 1, 2016 and December 31, 2019 were included. The cohorts were propensity score-matched 4:1 on baseline characteristics. Outcomes included intubation rates, intensive care unit (ICU) admission, length of stay (LOS), all-cause and seizure-related readmission, total hospitalization cost, and in-hospital mortality. A multivariable regression analysis was performed to determine the association between treatment and main outcomes adjusting for unbalanced confounders. Results: A total of 450 patients were analyzed (IV LEV, n = 360 vs. IV BRV, n = 90). Patients treated with IV BRV had lower crude prevalence of ICU admission (14.4 vs. 24.2%, P < 0.05), 30-day all-cause readmission (1.1 vs. 6.4%, P = 0.06), seizure-related 30-day readmission (0 vs. 4.2%, P < 0.05), similar mean total hospitalization costs ($13,715 vs. $13,419, P = 0.91), intubation (0 vs. 1.1%, P = 0.59), and in-hospital mortality (4.4 vs. 3.9%, P = 0.77). The adjusted odds for ICU admission (adjusted odds ratio [aOR] = 0.6; 95% confidence interval [CI]:0.31, 1.16; P = 0.13), 30-day all-cause readmission (aOR = 0.17; 95% CI:0.02, 1.24; P = 0.08), and in-hospital mortality (aOR = 1.15; 95% CI:0.37, 3.58, P = 0.81) were statistically similar between comparison groups. Conclusion: The use of IV BRV may provide an alternative to IV LEV for management of seizures in hospital setting due to lower or comparable prevalence of ICU admission, intubation, and 30-day seizure-related readmission. Additional studies with greater statistical power are needed to confirm these findings.

Association Between Adverse Events and Discontinuation of Antiepileptic Drugs Among Drug-Naïve Adults with Epilepsy.

BACKGROUND: Adherence to antiepileptic drugs (AEDs) remains the primary management tool to prevent recurrent seizures in patients with epilepsy. Adverse events associated with AEDs could have an impact on adherence and result in treatment failures. OBJECTIVE: The goal of this study was to assess the association between adverse events and discontinuation of AEDs for AED-naïve patients with epilepsy. Our second objective was to estimate the economic burden of AED discontinuation. METHODS: We retrospectively analyzed IBM MarketScan administrative data from 2014 to 2017. The cohort consisted of new users of AEDs with an epilepsy diagnosis and with two or more subsequent AED claims. Outpatient and inpatient cohorts were analyzed separately. Adverse events were identified by injury codes (E-CODES) or by International Classification of Diseases, Ninth/Tenth Edition (ICD-9/10) codes for disease manifestations reported in the literature or product inserts (LADE). Discontinuation of AEDs was defined as a gap of ≥ 60 days without a refill. All cost comparisons were based on 1:1 propensity-score matching. Associations between adverse events and discontinuation were estimated using logistic regression, adjusting for predefined covariates such as age, sex, Charlson Comorbidity Index, insurance type, and AED type. RESULTS: The overall discontinuation rate was 9% (E-CODES rate was 0.1% and LADE rate was 27%). The discontinued group was older (56.1 vs. 52.8 years; p < 0.0001). Adults aged ≥ 65 years had the highest discontinuation rate (11%). Patients who discontinued had fewer AED claims (6.8 vs. 9.2; p < 0.0001), more outpatient claims (19.3 vs. 17.8; p < 0.0001), and longer hospital stays (6.6 vs. 5.3 days; p < 0.0001). Differences in daily outpatient costs between patients with and without adverse events were statistically significant (E-CODES $US213 vs. 105; p = 0.001; LADE $US188 vs. 161; p < 0.0001). Additionally, total cost of AEDs in the outpatient cohort was higher for patients with adverse events (E-CODES and LADE). There was no association between E-CODES and AED discontinuation; however, there was a positive association between LADE and discontinuation in the outpatient cohort but a negative association in the inpatient cohort. CONCLUSION: We found that total costs of prescriptions claimed and total costs of outpatient visits among the outpatient cohort were higher for those with adverse drug events than for those without. An association between adverse events and discontinuation was inconclusive because it depended on the target population and how the adverse events were identified.

Cost of epilepsy-related health care encounters in the United States.

BACKGROUND: The cost of epilepsy is usually reported as total expenditure over a certain period. However, with the increased availability of acute treatments for use in the community setting, intermittent, single-seizure treatment is now possible in addition to the chronic epilepsy drug treatment paradigm. Data on the cost of discrete health care encounters are needed to substantiate the cost-benefit of these new treatments. OBJECTIVE: To estimate the health plan-paid costs of discrete epilepsy-related health care encounters in patients with epilepsy. METHODS: This retrospective cohort study utilized IBM MarketScan Commercial Claims, Medicare Supplemental and Coordination of Benefits (Medicare patients with supplemental insurance), and Multi-State Medicaid research databases. The primary analysis determined health plan-paid cost (adjudicated claims) of discrete epilepsy-related health care encounters, defined as having a primary diagnosis code of epilepsy or convulsion, from 2013 to 2018, in patients with epilepsy aged ≥ 12 years. Costs were adjusted to 2018 prices. Epilepsy cases were defined using ICD-CM codes. We excluded patients on capitated insurance plans as their cost per health care encounter is unknown. RESULTS: In total, 353,530 commercially insured, 378,051 Medicaid, and 69,176 Medicare plus supplemental insurance patients with epilepsy were included. More than 160,000 epilepsy-related emergency transportations, 225,000 emergency department (ED) visits, 49,000 hospitalizations, 700 urgent care visits, and ~2.5 million office visits were analyzed. 37.4% of epilepsy-related hospitalizations included care in the intensive care unit (ICU). In commercially insured patients, epilepsy-related health care encounters had median health plan-paid costs of $22,305 (Q1-Q3 = $14,336-$36,096, hospitalization); $3,375 ($565-$9,095, ICU visit); $1,913 ($417-$4,163, ED visit); $687 ($415-$1,083, emergency transportation); $95 ($23-$232, office visit); and $57 ($0-$171, urgent care visit). The median length of stay for epilepsy-related hospitalizations in working age, commercially insured patients was 4 (Q1-Q3 = 2-5) days. CONCLUSIONS: This is the first study to report health plan-paid cost per epilepsy-related health care encounter. These data can serve as a basis for more granular cost-benefit analyses of not only chronic but also acute treatments of epilepsy. DISCLOSURES: This analysis was funded by UCB Pharma. The sponsor had a role in the identification, design, conduct, and reporting of the analysis. Borghs, Beaty, Boudiaf, and Loewendorf are employees of UCB Pharma. Kalilani and Parekh were employees of UCB Pharma at the time of the analysis. Borghs, Beaty, and Loewendorf have received UCB Pharma stock from their employment. Kalilani and Parekh had received UCB Pharma stock at the time of employment, but no longer hold any. This work was presented in part as a poster at the 73rd Annual Meeting of the American Epilepsy Society; December 7, 2019; Baltimore, MD.

A Review of US Drug Costs Relevant to Medicare, Medicaid, and Commercial Insurers Post-Affordable Care Act Enactment, 2010-2016.

Since passage of the Affordable Care Act (ACA) in 2010, US stakeholders are increasingly being held accountable for the value of healthcare services and drugs administered to patients. Pharmacoeconomic analyses offer one method of demonstrating a product's value, yet there is a lack of resources specific to US drug costs relevant to each stakeholder. The aim of this study was to review current US drug costs (post-ACA). A literature review aimed at finding evidence on outpatient prescription drug costs was performed using the following sources: PubMed, governmental agencies, news websites, the Academy of Managed Care Pharmacy (AMCP) website, and Google Scholar. Articles were limited to those published in the years "2010-2016" and the "English" language, and those that described drug acquisition costs, reimbursement costs, and rebates or discounting for Medicare, Medicaid, and commercial payors. The Drug Cost Focus Group (DCFG) was convened to supplement the literature review; the DCFG provided their expertise on US drug costs and emerging issues affecting drug costs. ACA legislation increased drug rebates for manufacturers participating in the Medicaid Drug Rebate Program. Acquisition costs commonly referred to in the literature include the wholesale acquisition cost and average manufacture price. Drugs reimbursed by Medicaid are currently based on the actual acquisition cost and ACA-Federal Upper Limit. Evidence suggests that reimbursement methods in the public market are varied. Current gaps in the literature regarding commercial insurers' drug costs (post-ACA) present barriers to the application of relevant drug costs to pharmacoeconomic analyses.