PMID- 34621712
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211009
IS  - 2296-2360 (Print)
IS  - 2296-2360 (Electronic)
IS  - 2296-2360 (Linking)
VI  - 9
DP  - 2021
TI  - Combination Immunotherapy Use and Withdrawal in Pediatric Inflammatory Bowel 
      Disease-A Review of the Evidence.
PG  - 708310
LID - 10.3389/fped.2021.708310 [doi]
LID - 708310
AB  - Evidence-based guidelines have been developed outlining the concomitant use of 
      anti-tumor necrosis factor alpha (anti-TNF) agents and immunomodulators including 
      azathioprine (AZA) and methotrexate (MTX) in both adult and pediatric 
      populations. However, there exists a paucity of data guiding evidence-based 
      strategies for their withdrawal in pediatric patients in sustained remission. 
      This narrative review focuses on the available pediatric evidence on this 
      question in the context of what is known from the larger body of evidence 
      available from adult studies. The objective is to provide clarity and practical 
      guidance around who, what, when, and how to step down pediatric patients with 
      inflammatory bowel disease (IBD) from combination immunotherapy. Outcomes 
      following withdrawal of either of the two most commonly used anti-TNF therapies 
      [infliximab (IFX) or adalimumab (ADA)], or immunomodulator therapies, from a 
      combination regimen are examined. Essentially, a judicious approach must be taken 
      to identify a significant minority of patients who would benefit from treatment 
      rationalization. We conclude that step-down to anti-TNF (rather than 
      immunomodulator) monotherapy after at least 6 months of sustained clinical 
      remission is a viable option for a select group of pediatric patients. This group 
      includes those with good indicators of mucosal healing, low or undetectable 
      anti-TNF trough levels, lack of predictors for severe disease, and no prior 
      escalation of anti-TNF therapy. Transmural healing and specific human leukocyte 
      antigen (HLA) typing are some of the emerging targets and tools that may help 
      facilitate improved outcomes in this process. We also propose a simplified 
      evidence-based schema that may assist in this decision-making process. Further 
      pediatric clinical studies are required to develop the evidence base for 
      decision-making in this area.
CI  - Copyright (c) 2021 Meredith, Henderson, Wilson and Russell.
FAU - Meredith, Joseph
AU  - Meredith J
AD  - Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for 
      Children and Young People, Edinburgh, United Kingdom.
AD  - Child Life and Health, College of Medicine and Veterinary Medicine, University of 
      Edinburgh, Edinburgh, United Kingdom.
FAU - Henderson, Paul
AU  - Henderson P
AD  - Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for 
      Children and Young People, Edinburgh, United Kingdom.
AD  - Child Life and Health, College of Medicine and Veterinary Medicine, University of 
      Edinburgh, Edinburgh, United Kingdom.
FAU - Wilson, David C
AU  - Wilson DC
AD  - Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for 
      Children and Young People, Edinburgh, United Kingdom.
AD  - Child Life and Health, College of Medicine and Veterinary Medicine, University of 
      Edinburgh, Edinburgh, United Kingdom.
FAU - Russell, Richard K
AU  - Russell RK
AD  - Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for 
      Children and Young People, Edinburgh, United Kingdom.
AD  - Child Life and Health, College of Medicine and Veterinary Medicine, University of 
      Edinburgh, Edinburgh, United Kingdom.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210921
PL  - Switzerland
TA  - Front Pediatr
JT  - Frontiers in pediatrics
JID - 101615492
PMC - PMC8490777
OTO - NOTNLM
OT  - anti-TNF
OT  - combination therapy
OT  - drug withdrawal
OT  - immunomodulators
OT  - pediatric inflammatory bowel disease (PIBD)
COIS- DW has received speaker's fees, travel support, and participated in medical board 
      meetings with AbbVie, Roche, and Nestle Heath Sciences. RR has received speaker's 
      fees, travel support, and participated in medical board meetings with Abbvie, 
      Janssen, Takeda, Celltrion, Pharmacosmos, and Nestle. The remaining authors 
      declare that the research was conducted in the absence of any commercial or 
      financial relationships that could be construed as a potential conflict of 
      interest.
EDAT- 2021/10/09 06:00
MHDA- 2021/10/09 06:01
PMCR- 2021/09/21
CRDT- 2021/10/08 07:11
PHST- 2021/05/11 00:00 [received]
PHST- 2021/07/26 00:00 [accepted]
PHST- 2021/10/08 07:11 [entrez]
PHST- 2021/10/09 06:00 [pubmed]
PHST- 2021/10/09 06:01 [medline]
PHST- 2021/09/21 00:00 [pmc-release]
AID - 10.3389/fped.2021.708310 [doi]
PST - epublish
SO  - Front Pediatr. 2021 Sep 21;9:708310. doi: 10.3389/fped.2021.708310. eCollection 
      2021.