title: Intra-patient variability in adalimumab drug levels within and between cycles in Crohn's disease.
abstract: Whether therapeutic drug monitoring for adalimumab needs to be performed at trough has not been defined.
  
  
  
  To determine intra-patient adalimumab drug-level variation and to identify modulating patient and disease factors.
  
  
  
  In this prospective observational study, adult patients with Crohn's disease established on maintenance adalimumab had drug levels measured repeatedly according to pre-defined schedules (visit 1: day 4-6, visit 2: day 7-9, trough: day 13-14) across two consecutive fortnightly cycles. Disease activity was assessed using Harvey-Bradshaw Index, C-reactive protein and faecal calprotectin. For this analysis, trough levels ≥4.9 μg/mL were considered therapeutic.
  
  
  
  Nineteen patients underwent 111 evaluations. Mean intra-patient drug levels from paired visits between cycles did not differ (visit1 cycle1: 4.81, cycle2: 5.21 μg/mL, P = 0.24, visit2 cycle1: 4.86, cycle2: 4.82, P = 0.91 and trough cycle1: 3.95, cycle2: 3.95, P = 0.99), irrespective of disease activity. Drug levels were stable over the first 9 days (visit 1-2), but declined to trough by a mean 1.06 and 0.89 μg/mL between visit 1 or 2, respectively (P < 0.001). Models using nontemporal factors (smoking, syringe delivery device) and levels at earlier visits accounted for 66-80% of the variance in trough levels. On receiver-operating curve analysis, thresholds identified in the first 9 days that predicted a therapeutic trough level were similar to the trough threshold itself, with high sensitivity but modest specificity.
  
  
  
  While therapeutic drug monitoring should be performed at trough, a drug level ≥4.9 μg/mL obtained during the first 9 days predicts a therapeutic trough drug level with reasonable confidence.
authors.affiliation: Department of Gastroenterology, Alfred Hospital, Melbourne, Vic., Australia.|Department of Gastroenterology, Eastern Health, Melbourne, Vic., Australia.|Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Vic., Australia.
authors.forename: M G
authors.identifier: 0000-0002-2840-0108
authors.initials: MG
authors.lastname: Ward
authors.affiliation: Department of Gastroenterology, Alfred Hospital, Melbourne, Vic., Australia.
authors.forename: P A
authors.initials: PA
authors.lastname: Thwaites
authors.affiliation: Department of Gastroenterology, Eastern Health, Melbourne, Vic., Australia.
authors.forename: L
authors.initials: L
authors.lastname: Beswick
authors.affiliation: Department of Gastroenterology, Alfred Hospital, Melbourne, Vic., Australia.
authors.forename: J
authors.initials: J
authors.lastname: Hogg
authors.affiliation: Department of Gastroenterology, Alfred Hospital, Melbourne, Vic., Australia.
authors.forename: G
authors.initials: G
authors.lastname: Rosella
authors.affiliation: Department of Gastroenterology, Eastern Health, Melbourne, Vic., Australia.|Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Vic., Australia.
authors.forename: D
authors.initials: D
authors.lastname: Van Langenberg
authors.affiliation: Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Vic., Australia.
authors.forename: J
authors.initials: J
authors.lastname: Reynolds
authors.affiliation: Department of Gastroenterology, Alfred Hospital, Melbourne, Vic., Australia.|Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Vic., Australia.
authors.forename: P R
authors.initials: PR
authors.lastname: Gibson
authors.affiliation: Department of Gastroenterology, Alfred Hospital, Melbourne, Vic., Australia.|Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Vic., Australia.
authors.forename: M P
authors.initials: MP
authors.lastname: Sparrow
mesh_terms: D000068879:Adalimumab / Q000097:blood / Q000627:therapeutic use*; D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D003424:Crohn Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007206:Individuality; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D011379:Prognosis; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D002097:C-Reactive Protein; D000068879:Adalimumab