Clinical Use of Measuring Trough Levels and Antibodies against Infliximab in Patients with Pediatric Inflammatory Bowel Disease
1
조회
0
다운로드
3
인용
0
참고문헌
키워드
초록
Background/Aims: The clinical use of measuring infliximab (IFX) trough levels (TLs) and antibodies against IFX (ATIs) in patients with pediatric inflammatory bowel disease (IBD) remains unclear. We propose measuring these variables to create individual IFX treatment strategies for patients with pediatric IBD. Methods: This retrospective study was conducted in pediatric patients with IBD who received IFX from July 2009 to June 2014. Results: Samples were available from 39 patients with pediatric IBD. A significant difference was observed in IFX TLs in 16 patients who were in clinical remission (group A) after IFX therapy (median, 3.99 μg/ mL; interquartile range [IQR], 0.30 to 21.96) compared to 23 patients who had a poor response to treatment (group B) (median, 0.88 μg/mL; IQR, 0.00 to 6.80, p=0.002). In group B, 21 patients underwent empiric intensification of IFX treatment. After dose intensification, 17 patients had an improved response to treatment. Four patients still had no response to dose intensification. Therefore, these patients were switched to other biologics. Conclusions: Patients who had poor responses and subtherapeutic IFX TLs had an improved response to dose intensification. Patients who had ATIs were likely to continue to have no response after dose intensification. Therefore, tailoring individual IFX treatments based on IFX TLs, ATIs, and the clinical response should be considered.
Abstract
Background/Aims: The clinical use of measuring infliximab (IFX) trough levels (TLs) and antibodies against IFX (ATIs) in patients with pediatric inflammatory bowel disease (IBD) remains unclear. We propose measuring these variables to create individual IFX treatment strategies for patients with pediatric IBD. Methods: This retrospective study was conducted in pediatric patients with IBD who received IFX from July 2009 to June 2014. Results: Samples were available from 39 patients with pediatric IBD. A significant difference was observed in IFX TLs in 16 patients who were in clinical remission (group A) after IFX therapy (median, 3.99 μg/ mL; interquartile range [IQR], 0.30 to 21.96) compared to 23 patients who had a poor response to treatment (group B) (median, 0.88 μg/mL; IQR, 0.00 to 6.80, p=0.002). In group B, 21 patients underwent empiric intensification of IFX treatment. After dose intensification, 17 patients had an improved response to treatment. Four patients still had no response to dose intensification. Therefore, these patients were switched to other biologics. Conclusions: Patients who had poor responses and subtherapeutic IFX TLs had an improved response to dose intensification. Patients who had ATIs were likely to continue to have no response after dose intensification. Therefore, tailoring individual IFX treatments based on IFX TLs, ATIs, and the clinical response should be considered.
참고문헌 (24)
- Bosani M, "Biologic targeting in the treatment of inflammatory bowel diseases", Biologics, 3, pp.77~97 (2009)
- Rutgeerts P, "Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab)to maintain remission in Crohn’s disease", Gastroenterology, 117, pp.761~769 (1999)
- Hyams J, "Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn’s disease in children", Gastroenterology, 132, pp.863~873 (2007)
- Gisbert JP, "Loss of response and requirement of infliximab dose intensification in Crohn’s disease: a review.", Am J Gastroenterol, 104, pp.760~767 (2009)
- Ben-Horin S, "Review article: loss of response to anti-TNF treatments in Crohn’s disease", Aliment Pharmacol Ther, 33, pp.987~995 (2011)
- Matsuoka K, "Mechanism and therapeutic strategy of secondary failure to anti-tumor necrosis factor-alpha monoclonal antibody treatment for Crohn’s disease", Digestion, 88, pp.17~19 (2013)
- Scott FI, "Therapeutic drug monitoring of anti-TNF therapy in inflammatory bowel disease", Curr Treat Options Gastroenterol, 12, pp.59~75 (2014)
- Guerra I, "Management of inflammatory bowel disease in poor responders to infliximab", Clin Exp Gastroenterol, 7, pp.359~367 (2014)
- Baert F, "Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease", N Engl J Med, 348, pp.601~608 (2003)
- Maser EA, "Association of serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn’s disease", Clin Gastroenterol Hepatol, 4, pp.1248~1254 (2006)
- Seow CH, "Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis", Gut, 59, pp.49~54 (2010)
- Hyams JS, "Development and validation of a pediatric Crohn’s disease activity index", J Pediatr Gastroenterol Nutr, 12, pp.439~447 (1991)
- Turner D, "Consensus for managing acute severe ulcerative colitis in children: a systematic review and joint statement from ECCO, ESPGHAN, and the Porto IBD Working Group of ESPGHAN", Am J Gastroenterol, 106, pp.574~588 (2011)
- Hanauer SB, "Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial", Lancet, 359, pp.1541~1549 (2002)
- de Ridder L, "Infliximab dependency in pediatric Crohn’s disease: long-term follow-up of an unselected cohort", Inflamm Bowel Dis, 14, pp.353~358 (2008)
- Hyams JS, "Long-term outcome of maintenance infliximab therapy in children with Crohn’s disease", Inflamm Bowel Dis, 15, pp.816~822 (2009)
- De Bie CI, "The duration of effect of infliximab maintenance treatment in paediatric Crohn’s disease is limited", Aliment Pharmacol Ther, 33, pp.243~250 (2011)
- Klotz U, "Clinical pharmacokinetics and use of infliximab", Clin Pharmacokinet, 46, pp.645~660 (2007)
- Rutgeerts P, "Optimizing anti-TNF treatment in inflammatory bowel disease", Gastroenterology, 126, pp.1593~1610 (2004)
- Nanda KS, "4Impact 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, pp.40~47 (2013)
- Vande Casteele N, "Antibody response to infliximab and its impact on pharmacokinetics can be transient", Am J Gastroenterol, 108, pp.962~971 (2013)
- Afif W, "Clinical utility of measuring infliximab and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease", Am J Gastroenterol, 105, pp.1133~1139 (2010)
- Steenholdt C, "Cut-off levels and diagnostic accuracy of infliximab trough levels and anti-infliximab antibodies in Crohn’s disease", Scand J Gastroenterol, 46, pp.310~318 (2011)
- Steenholdt C, "Individualised therapy is more cost-effective than dose intensification in patients with Crohn’s disease who lose response to anti-TNF treatment: a randomised, controlled trial", Gut, 63, pp.919~927 (2014)
