Drug-Related Adverse Events Necessitating Treatment Discontinuation in Pediatric Inflammatory Bowel Disease Patients.
Journal
Journal of pediatric gastroenterology and nutrition
ISSN: 1536-4801
Titre abrégé: J Pediatr Gastroenterol Nutr
Pays: United States
ID NLM: 8211545
Informations de publication
Date de publication:
01 12 2022
01 12 2022
Historique:
pubmed:
30
9
2022
medline:
23
11
2022
entrez:
29
9
2022
Statut:
ppublish
Résumé
Inflammatory bowel disease (IBD) requires long-term drug therapy in most patients, posing a risk for adverse drug events with the need for discontinuation. In this study, we investigated adverse events (AE) necessitating drug discontinuation in pediatric and adolescent IBD patients. We used data prospectively collected from IBD patients below the age of 18 enrolled in the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS), namely demographic variables, medical characteristics, drug treatments, and related AE. We analyzed the frequency, type, and risk factors for AE necessitating drug discontinuation. A total of 509 pediatric IBD patients fulfilled the inclusion criteria of which 262 (51.5%) were diagnosed with Crohn disease (CD), 206 (40.5%) with ulcerative colitis (UC), and 41 (8%) with IBD-unclassified (IBD-U). In total, 132 (25.9%) presented with at least 1 drug-related AE that required drug cessation. Immunomodulators [methotrexate 29/120 (24.2%), azathioprine 57/372 (15.3%)] followed by tumor necrosis factor (TNF)-alpha antagonists [adalimumab 8/72 (11.1%), infliximab 22/227 (9.7%)] accounted for the highest proportions of AE necessitating treatment discontinuation. Treatment schemes with at least 3 concomitant drugs significantly amplified the risk for development of drug-related AE [odds ratio = 2.50, 95% confidence interval (1.50-4.17)] in all pediatric IBD patients. Drug-related AE necessitating discontinuation are common in pediatric and adolescent IBD patients. Caution needs to be taken in the case of concomitant drug use.
Identifiants
pubmed: 36171635
doi: 10.1097/MPG.0000000000003630
pii: 00005176-202212000-00011
pmc: PMC9645537
doi:
Substances chimiques
Infliximab
B72HH48FLU
Adalimumab
FYS6T7F842
Tumor Necrosis Factor-alpha
0
Tumor Necrosis Factor Inhibitors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
731-736Informations de copyright
Copyright © 2022 The Author(s). Published by Wolters Kluwer on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
Références
Guariso G, Gasparetto M. Treating children with inflammatory bowel disease: current and new perspectives. World J Gastroenterol. 2017;23:5469–85.
Walters TD, Kim M-O, Denson LA, et al. Increased effectiveness of early therapy with anti-tumor necrosis factor-alpha vs an immunomodulator in children with Crohn’s disease. Gastroenterology. 2014;146:383–91.
Rogler G. Gastrointestinal and liver adverse effects of drugs used for treating IBD. Best Pract Res Clin Gastroenterol. 2010;24:157–65.
Quezada SM, McLean LP, Cross RK. Adverse events in IBD therapy: the 2018 update. Expert Rev Gastroenterol Hepatol. 2018;12:1183–91.
Godat S, Fournier N, Safroneeva E, et al. Frequency and type of drug-related side effects necessitating treatment discontinuation in the Swiss Inflammatory Bowel Disease Cohort. Eur J Gastroenterol Hepatol. 2018;30:612–20.
Chaparro M, Ordas I, Cabre’ E, et al. Safety of thiopurine therapy in inflammatory bowel disease: long-term follow-up study of 3931 patients. Inflamm Bowel Dis. 2013;19:1404–10.
Chun JY, Kang B, Lee YM, Lee SY, Kim MJ, Choe YH. Adverse events associated with azathioprine treatment in Korean pediatric inflammatory bowel disease patients. Pediatr Gastroenterol Hepatol Nutr. 2013;16:171–7.
Gazouli M, Pachoula I, Panayotou I, et al. Thiopurine S-methyltransferase genotype and the use of thiopurines in paediatric inflammatory bowel disease Greek patients. J Clin Pharm Ther. 2010;35:93–7.
Spencer E, Norris E, Williams C, Dubinsky MC. The impact of thiopurine metabolite monitoring on the durability of thiopurine monotherapy in pediatric IBD. Inflamm Bowel Dis. 2019;25:142–9.
Lichtenstein GR, Feagan BG, Cohen RD, et al. Serious infection and mortality in patients with Crohn’s disease: more than 5 years of follow-up in the TREAT registry. Am J Gastroenterol. 2012;107:1409–22.
Wintzell V, Svanström H, Olén O, Melbye M, Ludvigsson JF, Pasternak B. Association between use of azathioprine and risk of acute pancreatitis in children with inflammatory bowel disease: a Swedish-Danish nationwide cohort study. Lancet Child Adolesc Health. 2019;3:158–65.
Pittet V, Michetti P, Mueller C, et al. Cohort profile update: the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). Int J Epidemiol. 2019;48:385–6f.
Pittet V, Juillerat P, Mottet C, et al. Cohort profile: the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). Int J Epidemiol. 2009;38:922–31.
Kotlyar DS, Osterman MT, Diamond RH, et al. A systematic review of factors that contribute to hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2011;9:36–41.e1.
Thayu M, Markowitz JE, Mamula P, Russo PA, Muinos WI, Baldassano RN. Hepatosplenic T-cell lymphoma in an adolescent patient after immunomodulator and biologic therapy for Crohn disease. J Pediatr Gastroenterol Nutr. 2005;40:220–2.
Dupont-Lucas C, Grandjean-Blanchet C, Leduc B, et al. Prevalence and risk factors for symptoms of methotrexate intolerance in pediatric inflammatory bowel disease. Inflamm Bowel Dis. 2017;23:298–303.
Benkov K, Lu Y, Patel A, et al. Role of thiopurine metabolite testing and thiopurine methyltransferase determination in pediatric IBD (vol 56, pg 333, 2013). J Pediatr Gastroenterol Nutr. 2013;56:582.
Murray A, Nguyen TM, Parker CE, Feagan BG, MacDonald JK. Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 2020;8:CD000544.
Corica D, Romano C. Renal involvement in inflammatory bowel diseases. J Crohns Colitis. 2016;10:226–35.
Grossi V, Lerer T, Griffiths A, et al. Concomitant use of immunomodulators affects the durability of infliximab therapy in children with Crohn’s disease. Clin Gastroenterol Hepatol. 2015;13:1748–56.
Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362:1383–95.
Siegel C, Finlayson SR, Sands BE, et al. Adverse events do not outweigh benefits of combination therapy for Crohn’s disease in a decision analytic model. Clin Gastroenterol Hepatol. 2012;10:46–51.
Schoepfer AM, Bortolotti M, Pittet V, et al. The gap between scientific evidence and clinical practice: 5-aminosalicylates are frequently used for the treatment of Crohn’s disease. Aliment Pharmacol Ther. 2014;40:930–7.
Sokollik C, Fournier N, Rizzuti D, et al. The use of 5-aminosalicylic acid in children and adolescents with inflammatory bowel disease. J Clin Gastroenterol. 2018;52:e87–91.
Ungaro RC, Limketkai BN, Jensen CB, et al. Stopping 5-aminosalicylates in patients with ulcerative colitis starting biologic therapy does not increase the risk of adverse clinical outcomes: analysis of two nationwide population-based cohorts. Gut. 2019;68:977–84.
Shaffer SR, Huang E, Patel S, Rubin DT. Cost-effectiveness of 5-aminosalicylate therapy in combination with biologics or tofacitinib in the treatment of ulcerative colitis. Am J Gastroenterol. 2021;116:125–33.
Scharl S, Barthel C, Rossel JB, et al. Malignancies in inflammatory bowel disease: frequency, incidence and risk factors-results from the Swiss IBD cohort study. Am J Gastroenterol. 2019;114:116–26.
Wijnands AM, de Jong ME, Lutgens MWMD, et al. Prognostic factors for advanced colorectal neoplasia in inflammatory bowel disease: systematic review and meta-analysis. Gastroenterology. 2021;160:1584–98.