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Potential Role Of Methotrexate Polyglutamates In Therapeutic Drug Monitoring For Pediatric Inflammatory Bowel Disease., Ryan Morrow, Ryan Funk, Mara Becker, Ashley K. Sherman, Leon Van Haandel, Taina Hudson, Rebecca Casini, Valentina Shakhnovich
Potential Role Of Methotrexate Polyglutamates In Therapeutic Drug Monitoring For Pediatric Inflammatory Bowel Disease., Ryan Morrow, Ryan Funk, Mara Becker, Ashley K. Sherman, Leon Van Haandel, Taina Hudson, Rebecca Casini, Valentina Shakhnovich
Manuscripts, Articles, Book Chapters and Other Papers
Inside cells, the immunomodulator methotrexate (MTX) undergoes the addition of glutamates to form methotrexate polyglutamates (MTX-Glu)-promising biomarkers of systemic exposure and treatment response to MTX in rheumatology. MTX-Glu are underexplored in Inflammatory Bowel Disease (IBD), with no data in pediatrics. In this cross-sectional secondary analysis, we assessed the relationships between MTX-Glu and MTX dose and treatment response in pediatric IBD. Twenty-one children with IBD, receiving maintenance therapy with infliximab (IFX) and MTX, had MTX-Glu1-6 concentrations and IFX troughs/antibodies measured and disease activity assessed for comparison in remission vs. active IBD using non-parametric tests, with associations explored using Spearman's correlation (ρ) …
Factors Associated With Reduced Infliximab Exposure In The Treatment Of Pediatric Autoimmune Disorders: A Cross-Sectional Prospective Convenience Sampling Study., Ryan S. Funk, Valentina Shakhnovich, Yu Kyoung Cho, Kishore Polireddy, Taina Hudson, Kyle Gress, Mara L. Becker
Factors Associated With Reduced Infliximab Exposure In The Treatment Of Pediatric Autoimmune Disorders: A Cross-Sectional Prospective Convenience Sampling Study., Ryan S. Funk, Valentina Shakhnovich, Yu Kyoung Cho, Kishore Polireddy, Taina Hudson, Kyle Gress, Mara L. Becker
Manuscripts, Articles, Book Chapters and Other Papers
BACKGROUND: Inadequate systemic exposure to infliximab (IFX) is associated with treatment failure. This work evaluated factors associated with reduced IFX exposure in children with autoimmune disorders requiring IFX therapy.
METHODS: In this single-center cross-sectional prospective study IFX trough concentrations and anti-drug antibodies (ADAs) were measured in serum from children diagnosed with inflammatory bowel disease (IBD) (n = 73), juvenile idiopathic arthritis (JIA) (n = 16), or uveitis (n = 8) receiving maintenance IFX infusions at an outpatient infusion clinic in a tertiary academic pediatric hospital. IFX concentrations in combination with population pharmacokinetic modeling were used to estimate IFX clearance. Patient …