title: Relapse after withdrawal from anti-TNF therapy for inflammatory bowel disease: an observational study, plus systematic review and meta-analysis.
abstract: Infliximab and adalimumab have established roles in inflammatory bowel disease (IBD) therapy. UK regulators mandate reassessment after 12 months' anti-TNF therapy for IBD, with consideration of treatment withdrawal. There is a need for more data to establish the relapse rates following treatment cessation.
  
  
  
  To establish outcomes following anti-TNF withdrawal for sustained remission using new data from a large UK cohort, and assimilation of all available literature for systematic review and meta-analysis.
  
  
  
  A retrospective observational study was performed on 166 patients with IBD (146 with Crohn's disease (CD) and 20 with ulcerative colitis [UC) and IBD unclassified (IBDU)] withdrawn from anti-TNF for sustained remission. Meta-analysis was undertaken of all published studies incorporating 11 further cohorts totalling 746 patients (624 CD, 122 UC).
  
  
  
  Relapse rates in the UK cohort were 36% by 1 year and 56% by 2 years for CD, and 42% by 1 year and 47% by 2 years for UC/IBDU. Increased relapse risk in CD was associated with age at diagnosis [hazard ratio (HR) 2.78 for age <22 years], white cell count (HR 3.22 for >5.25 × 109/L) and faecal calprotectin (HR 2.95 for >50 μg/g) at drug withdrawal. Neither continued immunomodulators nor endoscopic remission were predictors. In the meta-analysis, estimated 1-year relapse rates were 39% and 35% for CD and UC/IBDU respectively. Retreatment with anti-TNF was successful in 88% for CD and 76% UC/IBDU.
  
  
  
  Assimilation of all available data reveals remarkable homogeneity. Approximately one-third of patients with IBD flare within 12 months of withdrawal of anti-TNF therapy for sustained remission.
authors.affiliation: Edinburgh, UK.
authors.forename: N A
authors.identifier: 0000-0003-4368-1961
authors.initials: NA
authors.lastname: Kennedy
authors.affiliation: London, UK.
authors.forename: B
authors.initials: B
authors.lastname: Warner
authors.affiliation: London, UK.
authors.forename: E L
authors.initials: EL
authors.lastname: Johnston
authors.affiliation: London, UK.
authors.forename: L
authors.initials: L
authors.lastname: Flanders
authors.affiliation: London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Hendy
authors.affiliation: London, UK.
authors.forename: N S
authors.initials: NS
authors.lastname: Ding
authors.affiliation: Winchester, UK.
authors.forename: R
authors.initials: R
authors.lastname: Harris
authors.affiliation: London, UK.
authors.forename: A S
authors.initials: AS
authors.lastname: Fadra
authors.affiliation: Edinburgh, UK.
authors.forename: C
authors.initials: C
authors.lastname: Basquill
authors.affiliation: Newcastle Upon Tyne, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Lamb
authors.affiliation: Edinburgh, UK.|Glasgow, UK.
authors.forename: F L
authors.initials: FL
authors.lastname: Cameron
authors.affiliation: London, UK.
authors.forename: C D
authors.initials: CD
authors.lastname: Murray
authors.affiliation: Cambridge, UK.
authors.forename: M
authors.initials: M
authors.lastname: Parkes
authors.affiliation: Colchester, UK.
authors.forename: I
authors.initials: I
authors.lastname: Gooding
authors.affiliation: Exeter, UK.
authors.forename: T
authors.initials: T
authors.lastname: Ahmad
authors.affiliation: Glasgow, UK.
authors.forename: D R
authors.initials: DR
authors.lastname: Gaya
authors.affiliation: London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Mann
authors.affiliation: London, UK.
authors.forename: J O
authors.initials: JO
authors.lastname: Lindsay
authors.affiliation: Winchester, UK.
authors.forename: J
authors.initials: J
authors.lastname: Gordon
authors.affiliation: Edinburgh, UK.
authors.forename: J
authors.initials: J
authors.lastname: Satsangi
authors.affiliation: London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Hart
authors.affiliation: London, UK.
authors.forename: S
authors.initials: S
authors.lastname: McCartney
authors.affiliation: London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Irving
authors.affiliation: Edinburgh, UK.
authors.forename: C W
authors.initials: CW
authors.lastname: Lees
mesh_terms: D000068879:Adalimumab / Q000008:administration & dosage; D000328:Adult; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003424:Crohn Disease / Q000188:drug therapy*; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D000069285:Infliximab / Q000008:administration & dosage; D008297:Male; D016016:Proportional Hazards Models; D012008:Recurrence; D012189:Retrospective Studies; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab