Optimal Dosing for Biologic Agents in Obese Patients with Rheumatoid and Juvenile Arthritis

肥胖类风湿和幼年关节炎患者生物制剂的最佳剂量

• 批准号: 10670157
• 负责人: Stephen Joseph Balevic
• 金额: $ 16.61万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-26 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10670157
• 关键词: Acceleration; Adult; Affect; Agreement; Applications Grants; Arthritis; Biological; Biological Markers; Biological Products; Blood; Child; Childhood; Chronic Childhood Arthritis; Clinic; Clinical; Clinical Pharmacology; Clinical Research; Clinical Trials; Collaborations; Conduct Clinical Trials; Data; Databases; Development Plans; Disease; Doctor of Philosophy; Dose; Drug Kinetics; Drug usage; Effectiveness; Enrollment; Etanercept; Exposure to; Faculty; Failure; Foundations; Frequencies; Future; Goals; Individual; Inflammation; Inflammatory; Inflammatory Arthritis; International; K-Series Research Career Programs; Knowledge; Lead; Measures; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Modeling; Non obese; North Carolina; Obesity; Observational Study; Outcome; Pain; Participant; Patient Outcomes Assessments; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacologic Substance; Pharmacology; Physicians; Physiological; Physiology; Population; Protocols documentation; Public Health; Publications; Recording of previous events; Registries; Research; Research Institute; Research Personnel; Rheumatism; Rheumatoid Arthritis; Rheumatology; Safety; Sampling; Science; Scientist; Site; Statistical Data Interpretation; Structure; TNF gene; Techniques; Therapeutic; Therapeutic Uses; Training; Treatment Efficacy; Treatment Failure; Universities; adult obesity; career; career development; cytokine; design; disability; dose individualization; drug clearance; drug disposition; educational atmosphere; experience; improved; improved outcome; novel strategies; obese patients; obesity in children; pharmacodynamic model; pharmacokinetics and pharmacodynamics; prospective; response; skills; standard of care; success; tool; treatment optimization; treatment response; trial design; validation studies; virtual

PROJECT SUMMARY/ABSTRACT Rheumatoid arthritis (RA) and Juvenile Idiopathic Arthritis (JIA) are leading causes of pain and disability. While treatment with biologic agents may improve outcomes, treatment failure is common in patients who are obese. Despite the significant impact of treatment failure, it is currently unknown if the poor drug response in obesity is due to physiologic changes altering drug pharmacokinetics (PK)/Pharmacodynamics (PD), the underlying inflammatory state, or both. Dr. Balevic proposes to respond to this need by 1) characterizing the effects of obesity on disease activity and biomarkers of inflammation in a prospective observational study in RA and JIA; 2) using PK/PD modeling to investigate the effect of obesity on drug levels for a probe biologic agent, and relate drug levels to disease activity; and 3) using the PK/PD model to evaluate an optimal dosing strategy in a PK/PD clinical trial. This Mentored Career Development Award will provide a structured learning environment and expert mentorship to enable Dr. Stephen Balevic to develop as an independent investigator and future leader in the field of therapeutics for adults and children with rheumatic disease. Dr. Balevic’s overarching career goal is to optimize the dosing, safety, and effectiveness of medications by integrating clinical pharmacology and PK/PD modeling with drug trials. To achieve this goal, Dr. Balevic created a career development plan that capitalizes on the longstanding collaboration between Duke University, where he is junior faculty in the Divisions of Adult and Pediatric Rheumatology/Duke Clinical Research Institute, and the University of North Carolina at Chapel Hill, where he is pursuing a PhD in Pharmaceutical Sciences. In addition, Dr. Balevic will enhance his training in the regulatory conduct of clinical trials through a unique training agreement with the FDA. His short-term goals for the K23 program are: 1) to acquire advanced knowledge and skills in PK/PD modeling; 2) develop the professional skills and techniques to lead a clinical trials team; and 3) generate a critical mass of preliminary data and publications to support an R01 grant application. The mentorship team has a history of prior collaboration, a proven record of successful mentorship of junior faculty, and has internationally recognized expertise in biomarkers of drug response, obesity, PK/PD modeling, and clinical trials. Upon successful completion of this proposal, Dr. Balevic will have acquired the necessary skillset to pursue a lifelong career in promoting safe and effective use of drugs in adults and children with rheumatic disease.

项目总结/文摘

项目成果

Hydroxychloroquine PK and exposure-response in pregnancies with lupus: the importance of adherence for neonatal outcomes.

• DOI: 10.1136/lupus-2021-000602
• 发表时间: 2022-01
• 期刊: Lupus science & medicine
• 影响因子: 3.9
• 作者: Balevic SJ;Weiner D;Clowse MEB;Eudy AM;Maharaj AR;Hornik CP;Cohen-Wolkowiez M;Gonzalez D
• 通讯作者: Gonzalez D

Azathioprine metabolite levels and outcomes during pregnancies with rheumatic disease.

• DOI: 10.1136/lupus-2023-001036
• 发表时间: 2024-01-03
• 期刊: Lupus science & medicine
• 影响因子: 3.9

Hydroxychloroquine and COVID-19: a Rheumatologist's Take on the Lessons Learned.

• DOI: 10.1007/s11882-020-00983-9
• 发表时间: 2021-01-21
• 期刊: Current allergy and asthma reports
• 影响因子: 5.5
• 作者: Udupa A;Leverenz D;Balevic SJ;Sadun RE;Tarrant TK;Rogers JL
• 通讯作者: Rogers JL