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Therapeutics for Inflammatory Bowel Diseases in Children and Adolescents: A Focus on Biologics and an Individualized Treatment Paradigm

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Pediatric Pharmacotherapy

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 261))

Abstract

Pharmacologic treatment of children and adolescents with inflammatory bowel diseases (IBD) [Crohn’s disease and ulcerative colitis] requires consideration of disease and medication effects on growth and nutrition, the importance of durability of biologics, and concerns for long-term sequelae of disease and therapies. Achieving early remission in children with Crohn’s disease correlates with improved outcomes and therefore allows a window of opportunity for maximizing growth. Thus, there is a great need to treat children and adolescents with the right drug at the right time while achieving adequate exposure. Improved understanding of disease phenotypes, disease natural history, and risk stratification will play a critical role in treatment selection for children, particularly as more therapeutic options become available. Here we summarize data supporting newer concepts of treating the individual child with IBD through targeted early biologic treatment, including utilization of therapeutic drug monitoring to optimize treatment effects and the use of early antitumor necrosis factor (TNF)-α therapies to mitigate long-term sequelae of the disease. Recent inception cohort studies provide important data regarding the risk stratification of children and adolescents with IBD, which support a move toward a personalized therapeutic approach to IBD in children and adolescents.

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References

  • Ballengee CR, Stidham RW, Liu C et al (2018) Association between plasma level of collagen type III alpha 1 chain and development of strictures in pediatric patients with Crohn’s disease. Clin Gastroenterol. pii: S1542-3565(18)30969-8. https://doi.org/10.1016/j.cgh.2018.09.008. [Epub ahead of print]

  • Benchimol EI, Bernstein CN, Bitton A et al (2017) Trends in epidemiology of pediatric inflammatory bowel disease in Canada: distributed network analysis of multiple population-based provincial health administrative databases. Am J Gastroenterol 112(7):1120–1134

    PubMed  PubMed Central  Google Scholar 

  • Borrelli O, Bascietto C, Viola F et al (2004) Infliximab heals intestinal inflammatory lesions and restores growth in children with Crohn’s disease. Dig Liver Dis 36(5):342–347

    CAS  PubMed  Google Scholar 

  • Bossuyt P, Baert F, D’Heygere F et al (2019) Early mucosal healing predicts favorable outcomes in patients with moderate to severe ulcerative colitis treated with golimumab: data from the real-life BE-SMART cohort. Inflamm Bowel Dis 25(1):156–162

    PubMed  Google Scholar 

  • Brandse JF, Mould D, Smeekes O et al (2017) A real-life population pharmacokinetic study reveals factors associated with clearance and immunogenicity of infliximab in inflammatory bowel disease. Inflamm Bowel Dis 23(4):650–660

    PubMed  Google Scholar 

  • Buurman DJ, Maurer JM, Keizer RJ et al (2015) Population pharmacokinetics of infliximab in patients with inflammatory bowel disease: potential implications for dosing in clinical practice. Aliment Pharmacol Ther 42(5):529–539

    CAS  PubMed  Google Scholar 

  • Carman N, Tomalty D, Church PC et al (2019) Clinical disease activity and endoscopic severity correlate poorly in children newly diagnosed with Crohn’s disease. Gastrointest Endosc 89(2):364–372

    PubMed  Google Scholar 

  • Cheng J, Hamilton Z, Smyth M et al (2017) Concomitant therapy with immunomodulator enhances infliximab durability in pediatric inflammatory bowel disease. Inflamm Bowel Dis 23(10):1762–1773

    PubMed  Google Scholar 

  • Chi LY, Zitomersky NL, Liu E et al (2018) The impact of combination therapy on infliximab levels and antibodies in children and young adults with inflammatory bowel disease. Inflamm Bowel Dis 24(6):1344–1351

    PubMed  Google Scholar 

  • Church PC, Guan J, Walters TD et al (2014) Infliximab maintains durable response and facilitates catch-up growth in luminal pediatric Crohn’s disease. Inflamm Bowel Dis 20(7):1177–1186

    PubMed  Google Scholar 

  • Colombel JF, Sandborn WJ, Reinisch W et al (2010) Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med 362(15):1383–1395

    CAS  PubMed  Google Scholar 

  • Colombel JF, Rutgeerts P, Reinisch W et al (2011) Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. Gastroenterology 141(4):1194–1201

    CAS  PubMed  Google Scholar 

  • Colombel JF, Adedokun OJ, Gasink C et al (2018) Combination therapy with infliximab and azathioprine improves infliximab pharmacokinetic features and efficacy: a post hoc analysis. Clin Gastroenterol Hepatol. pii: S1542-3565(18)31024-3. https://doi.org/10.1016/j.cgh.2018.09.033. [Epub ahead of print]

  • Crombé V, Salleron J, Savoye G et al (2011) Long-term outcome of treatment with infliximab in pediatric-onset Crohn’s disease: a population-based study. Inflamm Bowel Dis 17(10):2144–2152

    PubMed  Google Scholar 

  • DoBoer MD, Lee AM, Herbert K et al (2018) Increases in IGF-1 after anti-TNF-α therapy are associated with bone and muscle accrual in pediatric crohn disease. J Clin Endocrinol Metab 103(3):936–945. https://doi.org/10.1210/jc.2017-01916

    Article  Google Scholar 

  • Dotan I, Ron Y, Yanai H et al (2014) Patient factors that increase infliximab clearance and shorten half-life in inflammatory bowel disease: a population pharmacokinetic study. Inflamm Bowel Dis 20(12):2247–2259

    PubMed  Google Scholar 

  • Dubinsky MC, Phan BL, Singh N et al (2017) Pharmacokinetic dashboard-recommended dosing is different than standard of care dosing in infliximab-treated pediatric IBD patients. AAPS J 19(1):215–222

    CAS  PubMed  Google Scholar 

  • Dubner SE, Shults J, Baldassano RN et al (2009) Longitudinal assessment of bone density and structure in an incident cohort of children with Crohn’s disease. Gastroenterology 136(1):123–130

    PubMed  Google Scholar 

  • El-Matary W, Walters TD, Huynh HQ et al (2019) Higher postinduction infliximab serum trough levels are associated with healing of fistulizing perianal Crohn’s disease in children. Inflamm Bowel Dis 25(1):150–155

    PubMed  Google Scholar 

  • Fasanmade AA, Adeodokun OJ, Blank M et al (2011) 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 33(7):946–964

    CAS  PubMed  Google Scholar 

  • Feuerstein JD, Nguyen GC, Kupfer SS et al (2017) American gastroenterological association institute guideline on therapeutic drug monitoring in inflammatory bowel disease. Gastroenterology 153(3):827–834

    PubMed  Google Scholar 

  • Gasparetto M, Guariso G (2014) Crohn’s disease and growth deficiency in children and adolescents. World J Gastroenterol 20(37):13219–13233

    CAS  PubMed  PubMed Central  Google Scholar 

  • Griffin LM, Thayu M, Baldassano RN et al (2015) Improvements in bone density and structure during anti-TNF-α therapy in pediatric Crohn’s disease. J Clin Endocrinol Metab 100(7):2630–2639

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hyams JS, Davis S, Mack DR et al (2017) Factors associated with early outcomes following standardised therapy in children with ulcerative colitis. Lancet Gastroenterol Hepatol 2(12):855–868

    PubMed  PubMed Central  Google Scholar 

  • Kerur B, Litman HJ, Stern JB et al (2017) Correlation of endoscopic disease severity with pediatric ulcerative colitis activity index score in children and young adults with ulcerative colitis. World J Gastroenterol 23(18):3322–3329

    PubMed  PubMed Central  Google Scholar 

  • Kerur B, Machan JT, Shapiro JM et al (2018) Biologics delay progression of Crohn’s disease, but not early surgery, in children. Clin Gastroenterol Hepatol 16(9):1467–1473

    PubMed  Google Scholar 

  • Kugathasan S, Denson LA, Walters TD et al (2017) Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study. Lancet 389(10080):1710–1718. https://doi.org/10.1016/S0140-6736(17)30317-3. Epub 2017 Mar 2

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee LYW, Sanderson JD, Irving PM (2012) Anti-infliximab antibodies in inflammatory bowel disease: prevalence, infusion reactions, immunosuppression and response, a meta-analysis. Eur J Gastroenterol Hepatol 24(9):1078–1085

    CAS  PubMed  Google Scholar 

  • Lega S, Dubinsky MC (2018) What are the targets of inflammatory bowel disease management. Inflamm Bowel Dis 24(8):1670–1675

    PubMed  Google Scholar 

  • Lega S, Phan BL, Rosenthal CJ et al (2019) Proactively optimized infliximab monotherapy is as effective as combination therapy in IBD. Inflamm Bowel Dis 25(1):134–141

    PubMed  Google Scholar 

  • Lichtenstein GR, Loftus EV, Isaacs KL et al (2018) ACG clinical guideline: management of crohn’s disease in adults. Am J Gastroenterol 113(4):481–517

    PubMed  Google Scholar 

  • Maser EA, Villela R, Silverberg MS et al (2006) Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn’s disease. Clin Gastroenterol Hepatol 4(10):1248–1254

    CAS  PubMed  Google Scholar 

  • Minar P, Saeed SA, Afreen M et al (2016) Practical use of infliximab concentration monitoring in pediatric Crohn disease. J Pediatr Gastroenterol Nutr 62(5):715–722

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mould DR, Dubinsky MC (2015) Dashboard systems: pharmacokinetic/pharmacodynamic mediated dose optimization for monoclonal antibodies. J Clin Pharmacol 55(Suppl 3):S51–S59

    CAS  PubMed  Google Scholar 

  • Nanda KS, Chiefetz AS, Moss AC (2013) Impact of antibodies to infliximab on clinical outcomes and serum infliximab levels in patients with inflammatory bowel disease (IBD): a meta-analysis. Am J Gastroenterol 108(1):40–47

    CAS  PubMed  Google Scholar 

  • Papamichael K, Juncadella A, Wong D et al (2019) Proactive therapeutic drug monitoring of adalimumab is associated with better long-term outcomes compared to standard of care in patients with inflammatory bowel disease. J Crohns Colitis. https://doi.org/10.1093/ecco-jcc/jjz018. [Epub ahead of print]

  • Pappa H, Thayu M, Sylvester F et al (2011) Skeletal health of children and adolescents with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 53(1):11–25

    PubMed  PubMed Central  Google Scholar 

  • Peyrin-Biroulet L, Sandborn W, Sands BE et al (2015) Selecting therapeutic targets in inflammatory bowel disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol 110(9):1324–1338

    CAS  PubMed  Google Scholar 

  • Ricciuto A, Dhaliwal J, Walters TD et al (2018) Clinical outcomes with therapeutic drug monitoring in inflammatory bowel disease: a systematic review with meta-analysis. J Crohns Colitis 12(11):1302–1315

    PubMed  Google Scholar 

  • Rosen MJ, Dhawan A, Saeed SA (2015) Inflammatory bowel disease in children and adolescents. JAMA Pediatr 169(11):1053–1060

    PubMed  PubMed Central  Google Scholar 

  • Rufo PA, Denson LA, Sylvester FA et al (2012) Health supervision in the management of children and adolescents with IBD: NASPGHAN recommendations. J Pediatr Gastroenterol Nutr 55(1):93–108

    PubMed  PubMed Central  Google Scholar 

  • Seow CH, Newman A, Irwin SP et al (2010) Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut 59(1):49–54

    CAS  PubMed  Google Scholar 

  • Spencer EA, Davis SM, Mack DR et al (2018) Serologic reactivity reflects clinical expression of ulcerative colitis in children. Inflamm Bowel Dis 24(6):1334–1343

    Google Scholar 

  • Thayu M, Leonard MB, Hyams JS et al (2008) Improvement in biomarkers of bone formation during infliximab therapy in pediatric Crohn’s disease: results of the REACH study. Clin Gastroenterol Hepatol 6(12):1378–1384

    CAS  PubMed  Google Scholar 

  • Ungar B, Levy I, Yavne Y et al (2016) Optimizing anti-TNF-α therapy: serum levels of infliximab and adalimumab are associated with mucosal healing in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 14(4):550–557

    CAS  PubMed  Google Scholar 

  • van de Casteele N, Ferrante M, Van Assche G et al (2015) Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology 148(7):1320–1329

    Google Scholar 

  • van de Casteele N, Jeyarajah J, Jairath V et al (2018) Infliximab exposure-response relationship and thresholds associated with endoscopic healing in patients with ulcerative colitis. Clin Gastroenterol Hepatol. pii: S1542-3565(18)31200-X. https://doi.org/10.1016/j.cgh.2018.10.036. [Epub ahead of print]

  • van Hoeve K, Dreesen E, Hoffman I et al (2018) Higher infliximab trough levels are associated with better outcome in paediatric patients with inflammatory bowel disease. J Crohns Colitis 12(11):1316–1325

    PubMed  Google Scholar 

  • Vaughn BP, Martinez-Vazquez M, Patwardhan VR et al (2014) Proactive therapeutic concentration monitoring of infliximab may improve outcomes for patients with inflammatory bowel disease: results from a pilot observational study. Inflamm Bowel Dis 20(11):1996–2003

    PubMed  PubMed Central  Google Scholar 

  • Walters TD, Kim MO, Denson LA et al (2014) Increased effectiveness of early therapy with anti-tumor necrosis factor-α vs an immunomodulator in children with Crohn’s disease. Gastroenterology 146(2):383–391

    CAS  PubMed  Google Scholar 

  • Walters TD, Faubion WA, Griffiths AM et al (2017) Growth impairment with adalimumab treatment in children with moderately to severely active Crohn’s disease. Inflamm Bowel Dis 23(6):967–975

    PubMed  Google Scholar 

  • Weinstein-Nakar I, Focht G, Church P et al (2018) Associations among mucosal and transmural healing and fecal level of calprotectin in children with Crohn’s disease. Clin Gastroenterol Hepatol 16(7):1089–1097

    CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Division of Gastroenterology, Hepatology, and Nutrition, Children’s National Medical Center, Washington, DC, USA

    Suruchi Batra

  2. George Washington University School of Medicine, Children’s National Medical Center, Washington, DC, USA

    Laurie S. Conklin

Authors
  1. Suruchi Batra
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  2. Laurie S. Conklin
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Corresponding author

Correspondence to Laurie S. Conklin .

Editor information

Editors and Affiliations

  1. Hospital for Children and Adolescents Center of Paediatric Research Department of Women and Child Health, University of Leipzig, Leipzig, Germany

    Wieland Kiess

  2. Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Department of Clinical Pharmacology, University Hospital Tüebingen, Tüebingen, Germany, Robert Bosch Gesellschaft fuer medizinische Forschung mbH, Stuttgart, Germany

    Matthias Schwab

  3. Children’s Hospital, University of Basel Children’s Hospital, Basel, Switzerland

    Johannes van den Anker

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Batra, S., Conklin, L.S. (2019). Therapeutics for Inflammatory Bowel Diseases in Children and Adolescents: A Focus on Biologics and an Individualized Treatment Paradigm. In: Kiess, W., Schwab, M., van den Anker, J. (eds) Pediatric Pharmacotherapy . Handbook of Experimental Pharmacology, vol 261. Springer, Cham. https://doi.org/10.1007/164_2019_255

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