Why are trough levels important

1. Bosani M, Ardizzone S, Porro GB. Biologic targeting in the treatment of inflammatory bowel diseases. Biologics. 2009;3:77–97. [PMC free article] [PubMed] [Google Scholar] Retracted

2. Rutgeerts P, D’Haens G, Targan S, et al. Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn’s disease. Gastroenterology. 1999;117:761–769. doi: 10.1016/S0016-5085(99)70332-X. [PubMed] [CrossRef] [Google Scholar]

3. 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. doi: 10.1053/j.gastro.2006.12.003. [PubMed] [CrossRef] [Google Scholar]

4. Gisbert JP, Panés J. Loss of response and requirement of infliximab dose intensification in Crohn’s disease: a review. Am J Gastroenterol. 2009;104:760–767. doi: 10.1038/ajg.2008.88. [PubMed] [CrossRef] [Google Scholar]

5. 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. doi: 10.1111/j.1365-2036.2011.04612.x. [PubMed] [CrossRef] [Google Scholar]

6. Matsuoka K, Kanai T. Mechanism and therapeutic strategy of secondary failure to anti-tumor necrosis factor-alpha monoclonal antibody treatment for Crohn’s disease. Digestion. 2013;88:17–19. doi: 10.1159/000351386. [PubMed] [CrossRef] [Google Scholar]

7. Scott FI, Lichtenstein GR. Therapeutic drug monitoring of anti-TNF therapy in inflammatory bowel disease. Curr Treat Options Gastroenterol. 2014;12:59–75. doi: 10.1007/s11938-013-0004-5. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

8. Guerra I, Bermejo F. Management of inflammatory bowel disease in poor responders to infliximab. Clin Exp Gastroenterol. 2014;7:359–367. [PMC free article] [PubMed] [Google Scholar]

9. Baert F, Noman M, Vermeire S, et al. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease. N Engl J Med. 2003;348:601–608. doi: 10.1056/NEJMoa020888. [PubMed] [CrossRef] [Google Scholar]

10. Maser EA, Villela R, Silverberg MS, Greenberg GR. Association of serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn’s disease. Clin Gastroenterol Hepatol. 2006;4:1248–1254. doi: 10.1016/j.cgh.2006.06.025. [PubMed] [CrossRef] [Google Scholar]

11. Seow CH, Newman A, Irwin SP, Steinhart AH, Silverberg MS, Greenberg GR. Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut. 2010;59:49–54. doi: 10.1136/gut.2009.183095. [PubMed] [CrossRef] [Google Scholar]

12. Hyams JS, Ferry GD, Mandel FS, et al. Development and validation of a pediatric Crohn’s disease activity index. J Pediatr Gastroenterol Nutr. 1991;12:439–447. doi: 10.1097/00005176-199105000-00005. [PubMed] [CrossRef] [Google Scholar]

13. Turner D, Travis SP, Griffiths AM, et al. 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. 2011;106:574–588. doi: 10.1038/ajg.2010.481. [PubMed] [CrossRef] [Google Scholar]

14. Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359:1541–1549. doi: 10.1016/S0140-6736(02)08512-4. [PubMed] [CrossRef] [Google Scholar]

15. de Ridder L, Rings EH, Damen GM, et al. Infliximab dependency in pediatric Crohn’s disease: long-term follow-up of an unselected cohort. Inflamm Bowel Dis. 2008;14:353–358. doi: 10.1002/ibd.20329. [PubMed] [CrossRef] [Google Scholar]

16. Hyams JS, Lerer T, Griffiths A, et al. Long-term outcome of maintenance infliximab therapy in children with Crohn’s disease. Inflamm Bowel Dis. 2009;15:816–822. doi: 10.1002/ibd.20845. [PubMed] [CrossRef] [Google Scholar]

17. De Bie CI, Hummel TZ, Kindermann A, et al. The duration of effect of infliximab maintenance treatment in paediatric Crohn’s disease is limited. Aliment Pharmacol Ther. 2011;33:243–250. doi: 10.1111/j.1365-2036.2010.04507.x. [PubMed] [CrossRef] [Google Scholar]

18. Klotz U, Teml A, Schwab M. Clinical pharmacokinetics and use of infliximab. Clin Pharmacokinet. 2007;46:645–660. doi: 10.2165/00003088-200746080-00002. [PubMed] [CrossRef] [Google Scholar]

19. Rutgeerts P, Van Assche G, Vermeire S. Optimizing anti-TNF treatment in inflammatory bowel disease. Gastroenterology. 2004;126:1593–610. doi: 10.1053/j.gastro.2004.02.070. [PubMed] [CrossRef] [Google Scholar]

20. Nanda KS, Cheifetz AS, Moss AC. 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. 2013;108:40–47. doi: 10.1038/ajg.2012.363. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

21. 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. doi: 10.1038/ajg.2013.12. [PubMed] [CrossRef] [Google Scholar]

22. Afif W, Loftus EV, Jr, Faubion WA, et al. Clinical utility of measuring infliximab and human antichimeric antibody concentrations in patients with inflammatory bowel disease. Am J Gastroenterol. 2010;105:1133–1139. doi: 10.1038/ajg.2010.9. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

23. Steenholdt C, Bendtzen K, Brynskov J, Thomsen OØ, Ainsworth MA. Cut-off levels and diagnostic accuracy of infliximab trough levels and anti-infliximab antibodies in Crohn’s disease. Scand J Gastroenterol. 2011;46:310–318. doi: 10.3109/00365521.2010.536254. [PubMed] [CrossRef] [Google Scholar]

24. Steenholdt C, Brynskov J, Thomsen OØ, et al. 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. 2014;63:919–927. doi: 10.1136/gutjnl-2013-305279. [PubMed] [CrossRef] [Google Scholar]


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Baseline Characteristics at Baseline Infliximab (n=39)

CharacteristicGroup A (n=16)Group B (n=23)p-value
Male sex12 (75)14 (61)0.4946
Crohn’s disease13 (81)16 (70)0.4798
 Location of disease
  Lower GI location0.6322
   L100
   L23 (23)2 (12.5)
   L310 (77)14 (87.5)
  Upper GI location0.7194
   No involvement9 (69)12 (75)
   L4a3 (23)2 (12.5)
   L4b1 (8)2 (12.5)
   L4a+b00
  Perianal fistulas10 (77)14 (87.5)0.6322
  PCDAI at IFX32.5 (17.5–55.0)31.3 (12.5–60.0)0.8259
Ulcerative colitis3 (19)7 (30)0.4798
 Location of disease1.0000
  E302 (29)
  E43 (100)5 (71)
 PUCAI at IFX65 (55–70)50 (35–65)NA
Age at diagnosis, yr14.5 (10.0–17.4)14.0 (7.4–18.5)0.3376
Age at IFX, yr14.7 (13.3–17.5)14.8 (9.0–18.8)0.7123
Duration from diagnosis to IFX infusion, mo3 (0.5–48)8 (0.2–37)0.4669
Concomitant IMM at start IFX16 (100)23 (100)NA
Concomitant mesalazine at start IFX16 (100)23 (100)NA
Corticosteroid use prior to IFX4 (25)13 (57)0.0994
Hematocrit, %37.0 (28.3–44.3)33.8 (26.0–44.2)0.1058
Albumin, g/dL4.0 (2.8–4.6)3.7 (2.3–4.5)0.3295
ESR, mm/hr50 (6–106)54 (21–99)0.5522
C-reactive protein, mg/dL1.14 (0.04–7.51)0.76 (0.05–7.12)0.9209