Paola Mina-Osorio’s research while affiliated with Regeneron and other places

Background Few large-scale international studies broadly characterized the burden of atopic dermatitis (AD) across age groups among children and adolescents. Objective To better characterize the AD burden in pediatric subjects by disease severity. Methods This cross-sectional, web-based survey of pediatric subjects (6 months to <18 years old) was conducted in 18 countries representing North America, Latin America, Europe, Middle East/Eurasia, and East Asia. Subjects with diagnosed AD were identified based on the International Study of Asthma and Allergies in Childhood criteria and self-/parent-report of ever being told by a physician that they/their child had eczema. AD severity was assessed using Patient Oriented Eczema Measure and Patient Global Assessment. Outcomes included measures of itch, skin pain, sleep, health-related quality-of-life (HRQoL), missed school days, and atopic comorbidities. Results The survey included 1489 children 6 months to < 6 years; 2898 children 6 to < 12 years; and 3078 adolescents 12 to < 18 years diagnosed with AD. Although the burden of mild AD was substantial, pediatric subjects with moderate or severe AD had more itch, skin pain, sleep problems, and impaired HRQoL, and missed more school days relative to those with mild AD; greater burden was observed among severe relative to moderate AD. At least one atopic comorbidity was present in 92·5% of all respondents. Conclusions These results highlight the burden of AD in pediatric subjects especially those with moderate-to-severe disease, and suggest the need for assessments that include the impact of AD on function and daily life.

BACKGROUND: Lupus nephritis (LN) is a common and severe complication of systemic lupus erythematosus (SLE), with approximately 40% of patients with SLE developing LN. Even with treatment, 10%-30% of patients will progress to end-stage renal disease (ESRD). Although many studies have assessed the clinical value of low disease activity in LN, the economic implications are less defined. OBJECTIVE: To evaluate treatment utilization and health care costs associated with active disease, low disease activity, and ESRD in patients with LN. METHODS: A retrospective analysis of Optum pharmacy and medical claims data from 2015 to 2019 was performed and included patients with a diagnosis of SLE (International Classification of Diseases, Ninth Revision or Tenth Revision codes 710.0 or M32, respectively) and additional prespecified criteria for LN. Total health care payer costs for medical and pharmacy services and treatment utilization for commonly prescribed medications were determined for periods of low disease activity, active disease, or ESRD. RESULTS: A total of 21,251 patients (mean age 60.3 years; 87% female; 55% White patients and 18% Black patients) with a mean follow-up period of 30.6 months were included; the majority of patients had active disease (67.3%), followed by low disease activity (51.3%), and ESRD (10.5%). Glucocorticoids were used 2 times more often and mycophenolate mofetil was used 4 times more often in patients with active disease vs low disease activity. Glucocorticoids, mycophenolate mofetil, and tacrolimus were more commonly used in patients with ESRD vs those with low disease activity. Mean medical costs were $4,777 per month in active disease and$18,084 per month in ESRD vs $2,523 per month in low disease activity. CONCLUSIONS: Treatment burden and costs are high for patients with active disease and ESRD in LN. Treatments that allow patients to achieve and maintain low disease activity may help improve patient outcomes and reduce medication use and overall health care costs. DISCLOSURES: Maria Dall'Era and Kenneth Kalunian are consultants of Aurinia Pharmaceuticals. Eric Turowski, Vanessa Birardi, Neil Solomons, Simrat Randhawa, and Paola Mina-Osorio are employees and stockholders of Aurinia Pharmaceuticals. Michael Eaddy is a former employee of Xcenda, LLC. Augustina Ogbonnaya and Eileen Farrelly are employees of Xcenda, LLC, which was contracted by Aurinia Pharmaceuticals to assist in the conduct of this study and the writing of this manuscript. Aurinia Pharmaceuticals provided funding for this study and the preparation of the manuscript. Aurinia Pharmaceuticals had a role in writing the report and decision to submit for publication.

The traditional drug development framework relies on target selection and disease classification criteria that are not designed to capture the entire universe of patients that could benefit from a novel therapy but the majority of patients with shared features of a disease. This framework fits the current model of clinical development and regulatory approval, but it must evolve when studying complex diseases which have multifactorial etiology and are associated with high levels of heterogeneity and diagnostic and scientific uncertainty. Our ability to treat complex diseases can only improve if we understand the multiple aspects of the endotype (i.e., underlying molecular mechanisms and clinical characteristics) and evaluate their influence on responses to treatment in discrete subgroups of patients. We must look toward a new era of clinical trial types in which modern data-driven approaches fueled by comprehensive sets of real-world data and evolving trends in patient selection and stratification allow us to increase the representativeness of real-world populations. We must meet the needs of more patients than those who fulfill strict diagnostic, classification, and response criteria that do not always reflect everyday clinical practice.KeywordsDrug developmentClinical trial innovationImmune-mediated diseasesReal-world evidenceImmune-mediated inflammatory diseasesComplex diseases

Objective: To evaluate the impact of atopic dermatitis on families of pediatric subjects. Study design: This cross-sectional, web-based survey of children/adolescents (6 months to <18 years old) with AD and their parents/caregivers was conducted in 18 countries encompassing North America, Latin America, Europe, Middle East/Eurasia, and East Asia. Children/adolescents with AD and their parents/caregivers were identified by the International Study of Asthma and Allergies in Childhood (ISAAC) criteria and ever being told by a physician that they had "eczema". AD severity was assessed using Patient Oriented Eczema Measure (POEM) and Patient Global Assessment. AD impact on families' lives was evaluated using the Dermatitis Family Impact questionnaire (DFI), and stand-alone questions on hours of AD-related care (past week) and missed work days (past 4 weeks) due to their child's AD. Results: A total of 7465 pairs of pediatric participants with AD and their parents/caregivers were surveyed. Across age groups, DFI total score for all regions ranged from 7.1-8.6, 13.2-14.9, and 17.0-17.2 for POEM mild, moderate, and severe AD, respectively; Subscale scores showed that higher AD severity had a greater impact on all family life domains, including sleep and tiredness. No specific patterns or trends were observed across age groups. Time spent on childcare and missed work days increased with AD severity. Conclusions: Across pediatric age groups and geographic regions, higher AD severity was associated with a greater negative impact on physical, emotional, social, and economic components of family life.

Background Voclosporin, a novel calcineurin inhibitor, has been tested successfully in two pivotal trials in adult patients with lupus nephritis. The Phase 3 AURORA 1 study and the Phase 2 AURA-LV study showed that compared with mycophenolate mofetil (MMF) and low-dose steroids alone, the addition of voclosporin significantly increased the complete renal response rate at approximately one year of treatment. Patients that completed the AURORA 1 study were eligible to enroll in the AURORA 2 extension study. Here we report the first interim analysis of AURORA 2. Methods AURORA 2 is a two-year, blinded, controlled extension study. Patients completing AURORA 1 continued the same randomized treatment in AURORA 2 of voclosporin (23.7 mg twice daily) or placebo, in combination with MMF (1 g twice daily) and low-dose steroids. The interim analysis evaluated urine protein creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) in patients with up to two years of total treatment. In total, 116 patients in the voclosporin arm and 100 patients in the control arm enrolled in the extension study, of which 73 patients in the voclosporin arm and 51 patients in the control arm received two years of treatment at the time of this interim analysis. Results Mean UPCR at pre-treatment AURORA 1 baseline was 3.9 mg/mg in the voclosporin arm (n=116) and 3.9 mg/mg in the control arm (n=100). The least square (LS) mean change in UPCR from pre-treatment AURORA 1 baseline to year two was -3.1 mg/mg for the voclosporin arm (n=73) and -2.1 mg/mg for control arm (n=51; figure 1). Mean corrected eGFR at pre-treatment AURORA 1 baseline was 79.6 mL/min/1.73 m² for the voclosporin arm (n=116) and 78.9 mL/min/1.73 m² for the control arm (n=100) and at year two, was 79.0 mL/min/1.73 m² for the voclosporin arm (n=73) and 82.9 mL/min/1.73 m² for the control arm (n=51). There was a small, expected, and early decrease in mean eGFR in the voclosporin arm in the first four weeks of treatment (in AURORA 1) after which eGFR remained stable throughout year one and year two. Additionally, there were no unexpected new adverse events observed in patients who continued with voclosporin treatment compared to control-treated patients. • Download figure • Open in new tab • Download powerpoint Abstract 514 Figure 1 UPCR change from baseline Mixed effects model for repeated measures (MMRM) analysis of least squares mean change from pre-treatment AURORA 1 baseline for UPCR included terms for baseline covariate, treatment, visit and treatment by visit interaction. Interim analysis of AURORA 2 patients includes data from pre-treatment baseline of AURORA 1, the one-year treatment period in AURORA 1 and up to one-year treatment period in AURORA 2. Conclusions Patients in the voclosporin treatment arm maintained meaningful reductions in proteinuria with no change in mean eGFR at two years of treatment. Additional AURORA 2 efficacy and safety data will be provided at the conclusion of the study. Acknowledgments Study funded by Aurinia Pharmaceuticals Inc. Trial Registration ClinicalTrials gov identifier: NCT03597464

Background Patients with atopic dermatitis (AD) are considered at increased risk of developing other type 2 inflammatory diseases. However, real-world evidence based on large US commercially insured pediatric populations is scarce. Objective To use a large US claims database (IBM® MarketScan® 2013-2017) to assess prevalence and incidence of type 2 inflammatory diseases in pediatric AD patients. Methods Pediatric AD patients were matched 1:1 to non-AD patients. Prevalence was assessed for conjunctivitis, rhinitis, urticaria, asthma, eosinophilic esophagitis and chronic rhinosinusitis/nasal polyps, 12 months post-index date (first AD diagnosis date for AD patients; a randomly selected outpatient visit for control patients). Incidence of other type 2 inflammatory diseases post-index was assessed among patients 0-2 years old. Results 244,776 AD and matched non-AD patients were selected. The prevalence and incidence of type 2 inflammatory diseases were higher among AD patients. Overall, the prevalence more than doubled for asthma, eosinophilic esophagitis, urticaria, and rhinitis, and increased with AD severity. Limitations AD identification based on billing diagnoses; observation period of only 12 months; limited to commercially insured patients Conclusion The burden of type 2 inflammatory diseases in pediatric AD patients is substantial, highlighting the need to optimize management of AD and its numerous associated morbidities.

Background Lupus nephritis (LN) is a common and severe manifestation of systemic lupus erythematosus (SLE) affecting 50% of SLE patients and leading to end-stage kidney disease (ESKD) in up to 30% of patients with LN. ¹ Previous studies have reported higher healthcare costs in patients with SLE that develop LN compared to patients without LN. ²⁻⁵ These studies captured overall treatment costs associated with LN, regardless of disease activity or severity, and were conducted in small patient populations. Objectives The aim of this study was to assess the real-world economic implications of achieving low disease activity compared to active disease or ESKD in a large LN population. Methods This study was a retrospective observational analysis of patients with LN within Optum’s health plan identified with ICD9 or ICD10 codes to have LN between January 1, 2015, and December 31, 2019. Patients were ≥18 years of age and had ≥2 months of follow-up data available. Patients were followed until death, loss to follow-up, or December 31, 2019. Low disease activity was defined by evidence of glucocorticoid doses ≤5 mg/day, evidence of mycophenolate mofetil (MMF) doses ≤2 g/day, and no use of cyclophosphamide for ≥6 consecutive months. Follow-up time that could not be defined as low disease activity was defined as active disease periods, except for periods with evidence of ESKD. Healthcare payer costs for medical and pharmacy services were compared between periods of low disease activity, active disease, and ESKD. A univariate generalized estimating equation model accounting for interdependence was used to compare differences in costs between periods of active and low disease activity. Results A total of 21,251 patients with LN met study criteria with a mean follow-up time of 31.0 months. The mean age was 60.3 years; 86.9% of patients were female and 35.2% of patients were non-White race. Low disease activity was evident in 51.3% of patients with a mean duration of 27.5 months. Mean monthly medical costs were $2,523 during periods of low disease activity and$4,777 during periods of active disease. After factoring in pharmacy costs, mean monthly total costs were $3,584 during periods of low activity and$6,612 during periods of active disease (P<0.001). The mean monthly costs of ESRD were $18,084 for medical and$3,760 for pharmacy. Conclusion Achieving low disease activity in patients with LN is associated with reduced economic burden to healthcare payers, with monthly medical costs averaging $2,254 less and total monthly costs averaging$3,028 less than costs during periods of active disease. References [1]Parikh SV et al. Update on Lupus Nephritis: Core Curriculum 2020. Am J Kidney Dis . 2020;76(2):265-281. [2]Bartels-Peculis L et al. Treatment patterns and health care costs of lupus nephritis in a United States payer population. Open Access Rheumatol . 2020;12:117-124. [3]Furst DE et al. Medical costs and healthcare resource use in patients with lupus nephritis and neuropsychiatric lupus in an insured population. J Med Econ . 2013;16(4):500-509. [4]Li T et al. Long-term medical costs and resource utilization in systemic lupus erythematosus and lupus nephritis: a five-year analysis of a large Medicaid population. Arthritis Rheum . 2009;61(6):755-763. [5]Pelletier EM et al. Economic outcomes in patients diagnosed with systemic lupus erythematosus with versus without nephritis: results from an analysis of data from a US claims database. Clin Ther . 2009;31(11):2653-2664. Disclosure of Interests Maria Dall’Era Speakers bureau: Consulting agreement with Aurinia for Advisory Boards and educational lectures, Tim Hermes Shareholder of: Aurinia Pharmaceuticals Inc., Employee of: Aurinia Pharmaceuticals Inc., Michael Eaddy Consultant of: Aurinia Pharmaceuticals Inc., Augustina Ogbonnaya Consultant of: Aurinia Pharmaceuticals Inc., Eileen Farrelly Consultant of: Aurinia Pharmaceuticals Inc., Paola Mina-Osorio Shareholder of: Aurinia Pharmaceuticals Inc., Employee of: Aurinia Pharmaceuticals Inc.