Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Infliximab in Pediatric Inflammatory Bowel Disease: A Systematic Review and Revised Dosing Considerations.
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:
06 2020
06 2020
Historique:
entrez:
23
5
2020
pubmed:
23
5
2020
medline:
22
6
2021
Statut:
ppublish
Résumé
Infliximab (IFX), a monoclonal antibody directed against tumor necrosis factor alpha is a potent treatment option for inflammatory bowel disease (IBD). Dosing regimens in children are extrapolated from adult data using a fixed, weight-based dose, which is often not adequate. While clinical trials have focused on safety and efficacy, there is limited data on pharmacokinetic characteristics and immunogenicity of IFX in children. The objective was to provide a systematic overview of current literature on pharmacokinetic and immunogenicity of IFX in children with IBD, to assess the validity of current adult to pediatric dosing extrapolation. A literature search identified publications up to October 2018. Eligibility criteria were study population consisting of children and/or adolescents with IBD, report of IFX trough levels and/or antibodies-to IFX, full text article or abstract, article in English, and original data. Initial electronic search yielded 2360 potentially relevant articles, with 1831 remaining after removal of duplicates. An additional search yielded another 202 potentially relevant articles. Of the 2033 retrieved articles, 2000 articles were excluded based on title, abstract, or eligibility criteria. Clearance of IFX was increased in young children and children with extensive disease, leading to lower trough levels after extrapolated dosing of 5 mg/kg, antibodies-to IFX emergence, and subsequent reduced efficacy. Adult to pediatric weight-based dosing extrapolation is often inadequate. We provide several considerations for optimal dosing of IFX in children and adolescents with IBD.
Identifiants
pubmed: 32443029
doi: 10.1097/MPG.0000000000002631
pii: 00005176-202006000-00012
doi:
Substances chimiques
Antibodies, Monoclonal
0
Gastrointestinal Agents
0
Tumor Necrosis Factor-alpha
0
Infliximab
B72HH48FLU
Types de publication
Journal Article
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
763-776Références
Breese EJ, Michie CA, Nicholls SW, et al. Tumor necrosis factor alpha-producing cells in the intestinal mucosa of children with inflammatory bowel disease. Gastroenterology 1994; 106:1455–1466.
Kennedy NA, Heap GA, Green HD, et al. Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn's disease: a prospective, multicentre, cohort study. Lancet Gastroenterol Hepatol 2019; 4:341–353.
Goldman JL, Davis HM, Zhou H, et al. Infliximab clearance in children: potential association with resting energy expenditure. Ann Paediatr Rheum 2012; 1:120–125.
Baldassano R, Braegger CP, Escher JC, et al. Infliximab (REMICADE) therapy in the treatment of pediatric Crohn's disease. Am J Gastroenterol 2003; 98:833–838.
Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet 2002; 359:1541–1549.
Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005; 353:2462–2476.
Hyams J, Crandall W, Kugathasan S, et al. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's disease in children. Gastroenterology 2007; 132:863–873.
Hyams J, Damaraju L, Blank M, et al. Induction and maintenance therapy with infliximab for children with moderate to severe ulcerative colitis. Clin Gastroenterol Hepatol 2012; 10:391–399.
Maser EA, Villela R, Silverberg MS, et al. Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn's disease. Clin Gastroenterol Hepatol 2006; 4:1248–1254.
Seow CH, Newman A, Irwin SP, et al. Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut 2010; 59:49–54.
Bortlik M, Duricova D, Malickova K, et al. Infliximab trough levels may predict sustained response to infliximab in patients with Crohn's disease. J Crohns Colitis 2013; 7:736–743.
Adedokun OJ, Sandborn WJ, Feagan BG, et al. Association between serum concentration of infliximab and efficacy in adult patients with ulcerative colitis. Gastroenterology 2014; 147:1296.e5–1307.e5.
Cornillie F, Hanauer SB, Diamond RH, et al. Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab: a retrospective analysis of the ACCENT I trial. Gut 2014; 63:1721–1727.
Vande Casteele N, Feagan BG, Gils A, et al. Therapeutic drug monitoring in inflammatory bowel disease: current state and future perspectives. Curr Gastroenterol Rep 2014; 16:378.
Vande Casteele N, Khanna R, Levesque BG, et al. The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn's disease. Gut 2015; 64:1539–1545.
Turner D, Ruemmele FM, Orlanski-Meyer E, et al. Management of paediatric ulcerative colitis, part 2: acute severe colitis-an evidence-based consensus guideline from the European Crohn's and Colitis Organization and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2018; 67:292–310.
Church PC, Ho S, Sharma A, et al. Intensified infliximab induction is associated with improved response and decreased colectomy in steroid-refractory paediatric ulcerative colitis. J Crohns Colitis 2019; 13:982–989.
Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6:e1000097.
Cardile S, Costa A, Loddo I, et al. Impact of measurement of infliximab and anti-infliximab antibodies levels in pediatric inflammatory bowel disease. Dig Liver Dis 2013; 45:e294–e295.
Rivera E, Liao C, Van’t Hof K, et al. Correlation between infliximab levels (IFX) and antibody to infliximab (ATI) in pediatric patients with inflammatory bowel disease (IBD) with the commercially available assay using electrochemilumescense. Gastroenterology 2014; 146:S782–S783.
Rosenthal C, Melmed G, Tripuraneni B, et al. Early infliximab trough levels predict remission at one year in pediatric IBD patients. Inflamm Bowel Dis 2012; 18:S5.
Schatz SB, Prell C, Freudenberg F, et al. Correlation of infliximab levels and antibodies with clinical outcome in children with IBD. J Pediatr Gastroenterol Nutr 2011; 52:E45.
Turon J, Langseder A, Irizarry R, et al. Clinical outcome of pediatric IBD patients after measurement of infliximab drug and anti-drug antibody levels. Gastroenterology 2013; 144:S-531.
Wilson C, Huffman S, McGoogan K. Common factors among children who developed antibodies to infliximab. Inflamm Bowel Dis 2013; 19:S98.
Adedokun OJ, Xu Z, Padgett L, et al. Pharmacokinetics of infliximab in children with moderate-to-severe ulcerative colitis: results from a randomized, multicenter, open-label, phase 3 study. Inflamm Bowel Dis 2013; 19:2753–2762.
Hadigan C, Baldassano R, Braegger C, et al. Pharmacokinetics of infliximab (Anti-TNFx) in children with Crohn's disease: a multicenter trial. J Pediatr Gastroenterol Nutr 1999; 29:525.
Mehrotra N, Garnett C, Zhang L, et al. Role of exposure-response analysis to guide dose selection in pediatric drug development when extrapolating efficacy from adults. Inflamm Bowel Dis 2011; 17:S5–S6.
Zitomersky NL, Atkinson BJ, Fournier K, et al. Antibodies to infliximab are associated with lower infliximab levels and increased likelihood of surgery in pediatric IBD. Inflamm Bowel Dis 2015; 21:307–314.
Chi LY, Zitomersky NL, Liu E, et al. The impact of combination therapy on infliximab levels and antibodies in children and young adults with inflammatory bowel disease. Inflamm Bowel Dis 2018; 24:1344–1351.
Candon S, Mosca A, Ruemmele F, et al. Clinical and biological consequences of immunization to infliximab in pediatric Crohn's disease. Clin Immunol 2006; 118:11–19.
Miele E, Markowitz JE, Mamula P. Human antichimeric antibody in children and young adults with inflammatory bowel disease receiving infliximab. J Pediatr Gastroenterol Nutr 2004; 38:502–508.
Minar P, Saeed SA, Afreen M, et al. Practical use of infliximab concentration monitoring in pediatric Crohn's disease. J Pediatr Gastroenterol Nutr 2016; 62:715–722.
Vahabnezhad E, Rabizadeh S, Dubinsky MC. A 10-year, single tertiary care center experience on the durability of infliximab in pediatric inflammatory bowel disease. Inflammatory Bowel Dis 2014; 20:606–613.
Choi SY, Kang B, Lee JH, et al. Clinical use of measuring trough levels and antibodies against infliximab in patients with pediatric inflammatory bowel disease. Gut Liver 2017; 11:55–61.
Deora V, Kozak J, El-Kalla M, et al. Therapeutic drug monitoring was helpful in guiding the decision-making process for children receiving infliximab for inflammatory bowel disease. Acta Paediatr 2017; 106:1863–1867.
Dubinsky MC, Phan BL, Singh N, et al. Pharmacokinetic dashboard-recommended dosing is different than standard of care dosing in infliximab-treated pediatric IBD patients. AAPS J 2017; 19:215–222.
Hofmekler T, Bertha M, McCracken C, et al. Infliximab optimization based on therapeutic drug monitoring in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2017; 64:580–585.
Kansen HM, Van Rheenen PF, Houwen RHJ, et al. Less anti-infliximab antibody formation in paediatric Crohn patients on concomitant immunomodulators. J Pediatr Gastroenterol Nutr 2017; 65:425–429.
Merras-Salmio L, Kolho KL. Clinical use of infliximab trough levels and antibodies to infliximab in pediatric patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2017; 64:272–278.
Rolandsdotter H, Marits P, Sundin U, et al. Serum-infliximab trough levels in 45 children with inflammatory bowel disease on maintenance treatment. Int J Mol Sci 2017; 18:pii: E575.
Burgess CJ, Reilly C, Steward-Harrison L, et al. Utility of proactive infliximab levels in paediatric Crohn's disease. Arch Dis Child 2019; 104:251–255.
Van Hoeve K, Dreesen E, Hoffman I, et al. Higher infliximab trough levels are associated with better outcome in paediatric patients with inflammatory bowel disease. J Crohns Colitis 2018; 12:1316–1325.
Hämäläinen A, Sipponen T, Kolho KL. Serum infliximab concentrations in pediatric inflammatory bowel disease. Scand J Gastroenterol 2013; 48:35–41.
Hoekman DR, Brandse JF, De Meij TG, et al. The association of infliximab trough levels with disease activity in pediatric inflammatory bowel disease. Scand J Gastroenterol 2015; 50:1110–1117.
Minar P, Jackson K, Tsai YT, et al. O-020 PMN CD64: therapeutic target for sustained remission during infliximab maintenance. Inflamm Bowel Dis 2016; 22: (suppl 1): S7.
Singh N, Rosenthal CJ, Melmed GY, et al. Early infliximab trough levels are associated with persistent remission in pediatric patients with inflammatory bowel disease. Inflammatory Bowel Dis 2014; 20:1708–1713.
El-Matary W, Walters TD, Huynh HQ, et al. Higher postinduction infliximab serum trough levels are associated with healing of fistulizing perianal Crohn's disease in children. Inflamm Bowel Dis 2019; 25:150–155.
Ohem J, Hradsky O, Zarubova K, et al. Evaluation of infliximab therapy in children with Crohn's disease using trough levels predictors. Dig Dis 2018; 36:40–48.
Stein R, Lee D, Leonard MB, et al. Serum infliximab, antidrug antibodies, and tumor necrosis factor predict sustained response in pediatric Crohn's disease. Inflamm Bowel Dis 2016; 22:1370–1377.
Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med 2004; 350:876–885.
Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med 2010; 362:1383–1395.
Reinisch W, Sandborn WJ, Rutgeerts P, et al. Long-term infliximab maintenance therapy for ulcerative colitis: the ACT-1 and -2 extension studies. Inflamm Bowel Dis 2012; 18:201–211.
Feuerstein JD, Nguyen GC, Kupfer SS, et al. American Gastroenterological Association Institute guideline on therapeutic drug monitoring in inflammatory bowel disease. Gastroenterology 2017; 153:827–834.
Vande Casteele N, Herfarth H, Katz J, et al. American Gastroenterological Association Institute technical review on the role of therapeutic drug monitoring in the management of inflammatory bowel diseases. Gastroenterology 2017; 153:835.e6–857.e6.
Yarur AJ, Kanagala V, Stein DJ, et al. Higher infliximab trough levels are associated with perianal fistula healing in patients with Crohn's disease. Aliment Pharmacol Ther 2017; 45:933–940.
Turner D, Koletzko S, Griffiths AM, et al. Use of placebo in pediatric inflammatory bowel diseases: a position paper from ESPGHAN, ECCO, PIBDnet, and the Canadian Children IBD Network. J Pediatr Gastroenterol Nutr 2016; 62:183–187.
Ruemmele FM, Hyams JS, Otley A, et al. Outcome measures for clinical trials in paediatric IBD: an evidence-based, expert-driven practical statement paper of the paediatric ECCO committee. Gut 2015; 64:438–446.
Shi R, Derendorf H. Pediatric dosing and body size in biotherapeutics. Pharmaceutics 2010; 2:389–418.
Fasanmade AA, Adedokun OJ, Ford J, et al. Population pharmacokinetic analysis of infliximab in patients with ulcerative colitis. Eur J Clin Pharmacol 2009; 65:1211–1228.
Van Limbergen J, Russell RK, Drummond HE, et al. Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease. Gastroenterology 2008; 135:1114–1122.
Kapel N, Meillet D, Favennec L, et al. Evaluation of intestinal clearance and faecal excretion of alpha 1-antiproteinase and immunoglobulins during Crohn's disease and ulcerative colitis. Eur J Clin Chem Clin Biochem 1992; 30:197–202.
Ordas I, Mould DR, Feagan BG, et al. Anti-TNF monoclonal antibodies in inflammatory bowel disease: pharmacokinetics-based dosing paradigms. Clin Pharmacol Ther 2012; 91:635–646.
Shapiro JM, Subedi S, Machan JT, et al. Durability of infliximab is associated with disease extent in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2016; 62:867–872.
Ben-Horin S, Chowers Y. Review article: loss of response to anti-TNF treatments in Crohn's disease. Aliment Pharmacol Ther 2011; 33:987–995.
Singh N, Dubinsky MC. Therapeutic drug monitoring in children and young adults with inflammatory bowel disease: a practical approach. Gastroenterol Hepatol 2015; 11:48–55.
De Ridder L, Rings EH, Damen GM, et al. Infliximab dependency in pediatric Crohn's disease: long-term follow-up of an unselected cohort. Inflammatory Bowel Dis 2008; 14:353–358.
Lichtenstein GR. Comprehensive review: antitumor necrosis factor agents in inflammatory bowel disease and factors implicated in treatment response. Therap Adv Gastroenterol 2013; 6:269–293.
Brandse JF, Strik AS, Mould D, et al. Insufficient infliximab exposure predisposes to immunogenicity and enhanced clearance of infliximab in IBD. J Crohns Colitis 2016; 10:S70–S71.
Vande Casteele N, Gils A, Singh S, et al. Antibody response to infliximab and its impact on pharmacokinetics can be transient. Am J Gastroenterol 2013; 108:962–971.
Dotan I, Ron Y, Yanai H, et al. Patient factors that increase infliximab clearance and shorten half-life in inflammatory bowel disease: a population pharmacokinetic study. Inflamm Bowel Dis 2014; 20:2247–2259.
Fasanmade AA, Adedokun OJ, Blank M, et al. Pharmacokinetic properties of infliximab in children and adults with Crohn's disease: a retrospective analysis of data from 2 phase III clinical trials. Clin Ther 2011; 33:946–964.
Marini JC, Sendecki J, Cornillie F, et al. Comparisons of serum infliximab and antibodies-to-infliximab tests used in inflammatory bowel disease clinical trials of remicade(R). AAPS J 2017; 19:161–171.
Vande Casteele N, Buurman DJ, Sturkenboom MG, et al. Detection of infliximab levels and anti-infliximab antibodies: a comparison of three different assays. Aliment Pharmacol Ther 2012; 36:765–771.
Van Bezooijen JS, Koch BC, Van Doorn MB, et al. Comparison of three assays to quantify infliximab, adalimumab, and etanercept serum concentrations. Ther Drug Monit 2016; 38:432–438.
Lu J, Van Stappen T, Spasic D, et al. Fiber optic-SPR platform for fast and sensitive infliximab detection in serum of inflammatory bowel disease patients. Biosens Bioelectron 2016; 79:173–179.
Targan SR, Hanauer SB, Van Deventer SJ, et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. N Engl J Med 1997; 337:1029–1035.
Maini R, St Clair EW, Breedveld F, et al. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet 1999; 354:1932–1939.
Van der Heijde D, Dijkmans B, Geusens P, et al. Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum 2005; 52:582–591.
Antoni C, Krueger GG, De Vlam K, et al. Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial. Ann Rheum Dis 2005; 64:1150–1157.
Reich K, Nestle FO, Papp K, et al. Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet 2005; 366:1367–1374.
Villanacci V, Antonelli E, Geboes K, et al. Histological healing in inflammatory bowel disease: a still unfulfilled promise. World J Gastroenterol 2013; 19:968–978.
Levesque BG, Greenberg GR, Zou G, et al. A prospective cohort study to determine the relationship between serum infliximab concentration and efficacy in patients with luminal Crohn's disease. Aliment Pharmacol Ther 2014; 39:1126–1135.
Feagan BG, Singh S, Lockton S, et al. Novel infliximab (IFX) and antibody-to-infliximab (ATI) assays are predictive of disease activity in patients with Crohn's disease (CD). Gastroenterology 2012; 142:S-114.