Low Anti-Tumor Necrosis Factor Levels During Maintenance Phase Are Associated With Treatment Failure in Children With Crohn's Disease.

Autor:	Moses J; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Stanford Medicine Children's Health, Palo Alto, CA, USA., Adler J; Division of Gastroenterology, Hepatology, and Nutrition, C.S. Mott's Children's Hospital, Ann Arbor, MI, USA.; Susan B. Meister Child Health Evaluation and Research Center, University of Michigan, Ann Arbor, MI, USA., Saeed SA; Department of Medical Affairs, Dayton Children's Hospital and Wright State University, Dayton, OH, USA., Firestine AM; Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Galanko JA; Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Ammoury RF; Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children's Hospital of The King's Daughters, Norfolk, VA, USA., Bass DM; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Stanford Medicine Children's Health, Palo Alto, CA, USA., Bass JA; Department of Gastroenterology, Hepatology, and Nutrition, Children's Mercy Kansas City, Kansas City, MO, USA., Bastidas M; Esoterix Specialty Laboratory, Labcorp, Calabasas, CA, USA., Benkov KJ; Division of Pediatric Gastroenterology, Icahn School of Medicine at Mt Sinai, New York, NY, USA., Bousvaros A; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA., Cabrera JM; Division of Pediatric Gastroenterology, Department of Pediatrics, Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WI, USA., Chun KY; Esoterix Specialty Laboratory, Labcorp, Calabasas, CA, USA., Dorsey JM; Pediatric Gastroenterology, Hepatology, and Nutrition, Nemours Children's Specialty Care, Jacksonville, FL, USA., Ebach DR; Division of Pediatric Gastroenterology, Hepatology, Pancreatology, and Nutrition, Department of Pediatrics, University of Iowa, Iowa City, IA, USA., Gulati AS; Department of Pediatrics and Pathology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Herfarth HH; Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Ivanova A; Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Jester TW; Department of Pediatrics, Division of Gastroenterology, University of Alabama at Birmingham, Birmingham, AL, USA., Kaplan JL; Division of Pediatric Gastroenterology, Mass General for Children and Harvard Medical School, Boston, MA, USA., Kusek ME; Division of Pediatric Gastroenterology, University of Nebraska Medical Center, Omaha, NE, USA., Leibowitz IH; Division of Gastroenterology, Hepatology and Nutrition, Children's National Medical Center, Department of Pediatrics, George Washington University, Washington, D.C., USA., Linville TM; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Levine Children's Hospital, Charlotte, NC, USA., Margolis PA; Cincinnati Children's Research Foundation Chair in Improvement Science, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Minar P; Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA., Molle-Rios Z; Division of Pediatric Gastroenterology, Nemours Children's Hospital, Wilmington, DE, USA., Niklinska-Schirtz BJ; Division of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, GA, USA., Olano KK; Division of Biostatistics and Epidemiology, Children's Hospital Medical Center, Cincinnati, OH, USA., Osaba L; Progenika Biopharma, a Grifols Company, Derio, Bizkaia, Spain., Palomo PJ; Division of Pediatric Gastroenterology, Nemours Children's Hospital, Orlando, FL, USA., Pashankar DS; Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA., Pitch L; ImproveCareNow Inc., Essex Junction, VT, USA., Samson CM; Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Washington University School of Medicine, St Louis, MO, USA., Sandberg KC; Division of Gastroenterology, Hepatology, and Nutrition, Dayton Children's Hospital, Dayton, OH, USA., Steiner SJ; Division of Pediatric Gastroenterology, Hepatology & Nutrition, Indiana University School of Medicine, Indianapolis, IN, USA., Strople JA; Division of Gastroenterology, Hepatology and Nutrition, Ann and Robert H. Lurie Children's Hospital of Chicago, Department of Pediatrics, Northwestern Feinberg School of Medicine, Chicago, IL, USA., Sullivan JS; The University of Vermont Children's Hospital and Department of Pediatrics, Larner College of Medicine, The University of Vermont, Burlington, VT, USA., Tung J; University of Oklahoma Children's Physicians, Pediatric Gastroenterology, Oklahoma City, OK, USA., Wali P; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, State University of New York, Upstate Medical University, Syracuse, NY, USA., Wohl DA; Division of Infectious Diseases, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Zikry M; Esoterix Specialty Laboratory, Labcorp, Calabasas, CA, USA., Boyle BM; Division of Gastroenterology, Hepatology, and Nutrition, Nationwide Children's Hospital, Columbus, OH, USA., Kappelman MD; Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jazyk:	angličtina
Zdroj:	Inflammatory bowel diseases [Inflamm Bowel Dis] 2024 Oct 17. Date of Electronic Publication: 2024 Oct 17.
DOI:	10.1093/ibd/izae239
Abstrakt:	Background: Higher drug levels and combination therapy with low-dose oral methotrexate (LD-MTX) may reduce anti-tumor necrosis factor (TNF) treatment failure in pediatric Crohn's disease. We sought to (1) evaluate whether combination therapy with LD-MTX was associated with higher anti-TNF levels, (2) evaluate associations between anti-TNF levels and subsequent treatment failure, and (3) explore the effect of combination therapy on maintenance of remission among patients with therapeutic drug levels (>5 µg/mL for infliximab and >7.5 µg/mL for adalimumab). Methods: We conducted a post hoc analysis of the COMBINE trial, which compared anti-TNF monotherapy to combination therapy with LD-MTX. We included participants who entered maintenance therapy and provided a serum sample approximately 4 months from randomization. Results: Among 112 infliximab and 41 adalimumab initiators, median drug levels were similar between combination therapy and monotherapy (infliximab: 8.8 vs 7.5 μg/mL [P = .49]; adalimumab: 11.1 vs 10.5 μg/mL [P = .11]). Median drug levels were lower in patients experiencing treatment failure (infliximab: 4.2 vs 9.6 μg/mL [P < .01]; adalimumab: 9.1 vs 12.3 μg/mL [P < .01]). Among patients treated with infliximab with therapeutic drug levels, we observed no difference in treatment failure between participants assigned monotherapy or combination therapy. Among patients treated with adalimumab, a trend towards reduced treatment failure in the combination therapy arm was not statistically significant (P = .14). Conclusions: LD-MTX combination was not associated with higher drug levels, but higher drug levels were associated with reduced risk of treatment failure. Among patients with therapeutic drug levels, we observed no benefit of LD-MTX for patients treated with infliximab. A nonsignificant trend towards reduced treatment failure with the addition of LD-MTX patients treated with adalimumab warrants further investigation. (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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