Review
Medicine, General & Internal
Pierre Quartier
Summary: Children with early onset juvenile idiopathic arthritis, especially with positive antinuclear antibodies, may develop chronic anterior uveitis, which requires regular slit lamp examination and prompt treatment. Therapy options range from local steroid treatment to systemic immunomodulatory therapy, tailored to individual patient needs, with involvement of expert ophthalmologists and pediatricians. Treatment should not be easily interrupted and may need to be intensified in certain cases for optimal disease control.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Ryan Sol Funk, Mara L. Becker
Summary: Variability in methotrexate efficacy poses a challenge in treating juvenile idiopathic arthritis. This study aimed to explore the impact of methotrexate on plasma metabolome and identify metabolic biomarkers of efficacy in children with JIA. The research revealed diverse metabolic changes following methotrexate initiation, including metabolites associated with microbial metabolism and exogenous sources.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Varvara Choida, Margaret Hall-Craggs, Bethany R. Jebson, Corinne Fisher, Maria Leandro, Lucy R. Wedderburn, Coziana Ciurtin
Summary: This study evaluated the role of biomarkers in predicting and assessing biologic treatment response and clinical remission in JIA, proposing new strategies for biomarker use. Various types of biomarkers were reviewed, identifying candidates with potential clinical utility and highlighting the need for new biomarker discovery and improved clinical applications.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Rheumatology
Imane Bardan, Karen M. Fagerli, Joe Sexton, Tore K. Kvien, Gunnstein Bakland, Pawel Mielnik, Yi Hu, Gunhild Lien, Berit Flato, Oyvind Molberg, Eirik K. Kristianslund, Anna-Birgitte Aga
Summary: This study compared the effectiveness of tumor necrosis factor inhibitors (TNFi) and comedication, as well as methotrexate (MTX) monotherapy, in patients with adult juvenile idiopathic arthritis (JIA) and rheumatoid arthritis (RA). The results showed that JIA patients had lower baseline disease activity compared to RA patients in different treatment groups. After baseline disease activity adjustment, there were no significant differences in disease activity change between JIA and RA patients for both treatment groups. TNFi and MTX monotherapy are both effective in adult JIA, with similar effectiveness to that shown in RA.
JOURNAL OF RHEUMATOLOGY
(2023)
Article
Pediatrics
Mikhail M. Kostik, Ekaterina V. Gaidar, Lubov S. Sorokina, Ilya S. Avrusin, Tatiana N. Nikitina, Eugenia A. Isupova, Irina A. Chikova, Yuri Yu. Korin, Elizaveta D. Orlova, Ludmila S. Snegireva, Vera V. Masalova, Margarita F. Dubko, Olga V. Kalashnikova, Vyacheslav G. Chasnyk
Summary: The presence of uveitis is a risk factor for JIA flare, while methotrexate can reduce the cumulative flare probability.
FRONTIERS IN PEDIATRICS
(2022)
Article
Multidisciplinary Sciences
Juan Carlos Nieto-Gonzalez, Laura Trives-Folguera, Alejandra Melgarejo-Ortuno, Aranzazu Ais, Belen Serrano-Benavente, Maria Sanjurjo, Jose Maria Alvaro-Gracia, Indalecio Monteagudo Saez
Summary: This study found that both persistence and adherence to biological therapy were remarkably high in JIA patients, and adherence to biological treatments could be related to a higher probability of patients achieving remission criteria within 6 months.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, General & Internal
Monika Ostrowska, Emil Michalski, Piotr Gietka, Malgorzata Manczak, Magdalena Posadzy, Iwona Sudol-Szopinska
Summary: This study compared MRI findings between patients clinically suspected of Juvenile Idiopathic Arthritis (JIA) and patients with ankle arthralgia of unknown cause. The results showed that inflammatory features were observed on MRI, with tenosynovitis being significantly more common in JIA patients. However, the MRI summarized score did not effectively differentiate between JIA and non-JIA patients.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Rheumatology
Joeri W. van Straalen, Goerkem Akay, Carlyn Kouwenberg, Sytze de Roock, Viera Kalinina Ayuso, Nico M. Wulffraat, Joke de Boer, Joost F. Swart
Summary: This study investigated the effect of methotrexate (MTX) therapy on new-onset uveitis in patients with biological-naive juvenile idiopathic arthritis (JIA). The results showed that MTX was associated with a significantly reduced new-onset uveitis rate in patients with JIA. Clinicians should consider early initiation of MTX in high-risk patients and increase ophthalmologic screening after MTX discontinuation.
Article
Medicine, General & Internal
Ana Carolina Londe, Jaqueline Cristina de Amorim, Paulo Rogerio Julio, Nico M. Wulffraat, Roberto Marini, Simone Appenzeller
Summary: The study aimed to translate and validate the Methotrexate (MTX) Intolerance Severity Score (MISS) questionnaire into Brazilian Portuguese for children and adolescents. The findings showed that MISS is a feasible and practical tool for routine clinical care to identify MTX intolerance in JIA.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Nutrition & Dietetics
Maciej K. Stawicki, Adrian Goralczyk, Justyna Mlynczyk, Anna Kondratiuk, Jerzy Konstantynowicz
Summary: This study evaluated the prevalence of vitamin D deficiency in children with juvenile idiopathic arthritis (JIA) and found that vitamin D deficiency is independent of disease activity or inflammatory markers. However, MTX treatment may lead to inadequate vitamin D levels. Therefore, vitamin D supplementation should be considered for all children receiving long-term MTX therapy.
Article
Ophthalmology
Sanna Leinonen
Summary: This perspective aimed to explore the screening of uveitis in Nordic children with JIA, summarizing the predictors and recommendations for JIA-uveitis screening. Younger age, positive antinuclear antibody titre, specific subtypes of JIA, and shorter duration of JIA are predictors of uveitis in JIA. Methotrexate and monoclonal TNF inhibitor treatment can reduce the risk of JIA-uveitis. Guidelines for screening intervals and length were prepared based on known risk factors and the Nordic population.
ACTA OPHTHALMOLOGICA
(2023)
Article
Rheumatology
Camilla Wibrand, Nini Kyvsgaard, Anne Estmann Christensen, Troels Herlin
Summary: This study aimed to investigate the association between ALT levels during MTX treatment and MTX intolerance in JIA. The results showed no significant difference in ALT levels between the MTX intolerant group and the MTX tolerant group. However, only MTX intolerant girls showed elevated ALT levels. The intolerant girls also had a higher intolerance severity score compared to the intolerant boys.
RHEUMATOLOGY INTERNATIONAL
(2023)
Article
Ophthalmology
Francesca Tirelli, Maria Elisabetta Zannin, Fabio Vittadello, Jacopo Agnolucci, Monica Mazzarolo, Francesco Zulian
Summary: The study evaluated the long-term efficacy of MTX monotherapy in patients with JIA-U and found that although effective in the early stages, MTX showed poor disease control in the long term, with many patients eventually needing biologic agents for treatment.
OCULAR IMMUNOLOGY AND INFLAMMATION
(2022)
Review
Rheumatology
Claas H. Hinze, Dirk Foell, Christoph Kessel
Summary: Systemic juvenile idiopathic arthritis (sJIA) is a disease characterized by severe systemic inflammation and arthritis. It poses challenges to rheumatologists treating pediatric and adult patients worldwide. Although treatment plans exist for classic sJIA, there is still a lack of clear treatment approaches for early sJIA without arthritis and complicated sJIA.
NATURE REVIEWS RHEUMATOLOGY
(2023)
Article
Pediatrics
Sara Della Paolera, Serena Pastore, Alen Zabotti, Alberto Tommasini, Andrea Taddio
Summary: The role of musculoskeletal ultrasound in diagnosing tenosynovitis in JIA patients is proven to be practical. More than half of the patients with ankle swelling were found to have tenosynovitis, with about 50% of them not showing sonographic signs of active joint synovitis. Biological therapy alone or in combination with DMARDs has shown effectiveness in inducing remission in tenosynovitis patients.
Article
Obstetrics & Gynecology
Devika Maulik, Leon van Haandel, Jenifer Allsworth, Kris S. Chaisanguanthum, John D. Yeast, J. Steven Leeder
Summary: This study aimed to investigate the effects of race and supplementation on the concentration and correlation of various folate species in maternal and umbilical cord blood. Results showed that folate concentrations in umbilical cord plasma were consistently higher than maternal samples, particularly for 5MTHF.
JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Kristine R. Crews, Andrew A. Monte, Rachel Huddart, Kelly E. Caudle, Evan D. Kharasch, Andrea Gaedigk, Henry M. Dunnenberger, J. Steven Leeder, John T. Callaghan, Caroline Flora Samer, Teri E. Klein, Cyrine E. Haidar, Sara L. Van Driest, Gualberto Ruano, Katrin Sangkuhl, Larisa H. Cavallari, Daniel J. Muller, Cynthia A. Prows, Mohamed Nagy, Andrew A. Somogyi, Todd C. Skaar
Summary: Opioids are commonly used for the treatment of acute and chronic pain, and the clinical effects and adverse events are associated with genes such as CYP2D6, OPRM1, and COMT. While there is extensive research on the association between CYP2D6 and codeine/tramadol, data for hydrocodone, oxycodone, methadone, OPRM1, and COMT are more limited.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Pharmacology & Pharmacy
Brian D. Chapron, Alenka Chapron, J. Steven Leeder
Summary: Developmental changes in childhood impact drug disposition, with advancements in understanding over the past 20 years driven by technological progress in mass spectrometry and in silico tools. However, gaps in research evidence highlight areas where further characterization of developmental trends in drug disposition is needed.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Chelsea Hosey-Cojocari, Sherwin S. Chan, Chance S. Friesen, Amie Robinson, Veronica Williams, Erica Swanson, Daniel O'Toole, Jansynn Radford, Neil Mardis, Trevor N. Johnson, J. Steven Leeder, Valentina Shakhnovich
Summary: The liver is the primary organ responsible for clearing most drugs, the clearance capacity is related to organ size and growth in children. Equations relating body surface area and liver volume can adequately estimate liver volumes in children, regardless of weight status.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2021)
Review
Pharmacology & Pharmacy
Daniel L. Hertz, Laura B. Ramsey, Mathangi Gopalakrishnan, J. Steven Leeder, Sara L. Van Driest
Summary: Pharmacogenetics aims to select the right drug and dose for each patient to optimize therapeutic outcomes, with a focus on pharmacokinetics. Efforts to discover and validate pharmacogenetics-pharmacodynamics associations without the confounding of pharmacokinetic variability could provide valuable insights for future analyses.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Pharmacology & Pharmacy
Stephani L. Stancil, Whitney Nolte, Robin E. Pearce, Vincent S. Staggs, J. Steven Leeder
Summary: This study aimed to investigate the factors influencing the biotransformation of naltrexone. The results showed that there is significant variability in naltrexone biotransformation in both children and adults, and it is influenced by age, sex, and genetic variation.
DRUG METABOLISM AND DISPOSITION
(2022)
Article
Pharmacology & Pharmacy
Deepak Ahire, Abdul Basit, Lisa J. Christopher, Ramaswamy Iyer, J. Steven Leeder, Bhagwat Prasad
Summary: The mitochondrial amidoxime-reducing component (mARC) enzymes, which metabolize various substances, were quantified in different tissues using targeted proteomics. The abundance of mARC1 and mARC2 in the liver, kidney, intestine, and lung was determined, and their levels were found to be independent of age and sex. These findings provide important information for developing pharmacokinetic models and predicting the metabolism of mARC substrates in vivo.
DRUG METABOLISM AND DISPOSITION
(2022)
Article
Pharmacology & Pharmacy
Xiaoyan Chu, Bhagwat Prasad, Sibylle Neuhoff, Kenta Yoshida, James Steven Leeder, Dwaipayan Mukherjee, Kunal Taskar, Manthena V. S. Varma, Xinyuan Zhang, Xinning Yang, Aleksandra Galetin
Summary: The role of membrane transporters in pharmacokinetics, drug-drug interactions, pharmacodynamics, and drug toxicity is widely recognized. This article highlights recent advances in the study of changes in transporter expression and activity in various diseases and specific populations, with a focus on clinical implications.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Pharmacology & Pharmacy
Andrew C. Behrle, Justin Douglas, J. Steven Leeder, Leon van Haandel
Summary: CYP2D6 is an important enzyme involved in the metabolism of clinically used drugs. This study aimed to identify an endogenous urinary biomarker of CYP2D6 activity. The researchers isolated and purified a substance called M1 from urine, and found that it has a similar structure to solanidine, a nitrogen-containing steroidal alkaloid. This discovery may have implications for assessing CYP2D6 activity and guiding treatment with drugs metabolized by this enzyme.
DRUG METABOLISM AND DISPOSITION
(2022)
Article
Medicine, Research & Experimental
J. Steven Leeder, Andrea Gaedigk, Krista J. Wright, Vincent S. Staggs, Sarah E. Soden, Yvonne S. Lin, Robin E. Pearce
Summary: This study aimed to investigate the relative contributions of genetic variation, growth, and development on CYP2D6 activity during puberty. Through a three-year longitudinal study on healthy children and adolescents aged 7-15 years, it was found that CYP2D6 genotype was the most important factor contributing to the variability in CYP2D6 activity during puberty, while age and pubertal development had minimal effects. The use of genotype-based dosing guidelines should be considered for CYP2D6 substrates in pediatric patients.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Pablo Zubiaur, Paula Soria-Chacartegui, Erin C. C. Boone, Bhagwat Prasad, Jean Dinh, Wendy Y. Y. Wang, Santiago Zugbi, Andrea Rodriguez-Lopez, Eva Gonzalez-Iglesias, J. Steven Leeder, Francisco Abad-Santos, Andrea Gaedigk
Summary: A novel haplotype, CYP2C:TG, composed of two non-coding variants, was found to be associated with ultrarapid metabolism of CYP2C19 substrates. However, further analysis revealed that the CYP2C:TG haplotype had no significant effect on the pharmacokinetics of these substrates or the protein abundance and activity of CYP2C8, CYP2C9, CYP2C18, and CYP2C19. On the other hand, CYP2C19 intermediate and poor metabolizers showed distinct differences compared to normal, rapid, and ultrarapid metabolizers. In conclusion, there is insufficient evidence to support the clinical testing of the CYP2C:TG haplotype for drug therapy.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Clinical Neurology
Rose Gelineau-Morel, Christopher Smyser, J. Steven Leeder
Summary: The recent focus on improving recognition of dystonia in cerebral palsy (DCP) has highlighted the need for more effective treatments. Current pharmacologic recommendations for DCP are based on anecdotal evidence, with minimal to moderate improvements in dystonia. Precision therapeutics can improve treatment outcomes through predictive biomarker identification, patient stratification, individualized interventions, and monitoring of response.
Meeting Abstract
Pharmacology & Pharmacy
V. Shakhnovich, S. Abdel-Rahman, S. Chan, N. Mardis, R. Pearce, V. Williams, C. Friesen, J. Radford, J. Leeder
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Meeting Abstract
Pharmacology & Pharmacy
J. Wagner, J. Leeder, G. Reed, N. Zhang, A. Galetin
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Meeting Abstract
Pharmacology & Pharmacy
J. Wagner, J. Leeder, G. Reed, N. Zhang, A. Galetin
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
