title: Concurrent immunomodulator therapy is associated with higher adalimumab trough levels during scheduled maintenance therapy.
abstract: BACKGROUND
  Combination therapy with infliximab and immunomodulators is superior to monotherapy, resulting in better outcomes and higher trough levels of infliximab. The role of concurrent immunomodulatory therapy on adalimumab trough levels has not been adequately investigated. We evaluated the impact of concomitant immunomodulation on adalimumab trough levels in patients on scheduled maintenance therapy.
  
  
  METHODS
  We conducted a prospective observational, cross-sectional study of all inflammatory bowel disease patients on maintenance therapy who had adalimumab trough levels measured between January 2013 and January 2016. Drug level and anti-drug antibody measurements were performed on sera using a solid phase assay. Pairwise comparison of means was used to compare trough levels in patients with and without concomitant immune modulator therapy.
  
  
  RESULTS
  In total, 79 patients were included. Twenty-three patients (29.1%) were on weekly dosing whereas 56 (70.9%) were on alternate weeks. Median adalimumab trough levels were comparable in patients with and without clinical remission (6.8 μg/ml (IQR 5.6-8.1) versus 6.7 μg/ml (IQR 3.9-8.1), respectively. Patients with an elevated faecal calprotectin >250 μg/g had lower adalimumab trough levels (median 6.7, IQR 3.9-8) compared to patients with faecal calprotectin <250 μg/g (median 7.7, IQR 6.1-8.1) though this did not achieve statistical significance (p = .062). Median adalimumab trough levels among patients on concurrent immunomodulators was 7.2 μg/ml (IQR 5.7-8.1) compared to those not on concurrent immunomodulator, 6.1 μg/ml (IQR 2.7-7.7, p = .0297).
  
  
  CONCLUSIONS
  Adalimumab trough levels were significantly higher in patients on concurrent immunomodulators during maintenance therapy. There was a trend towards a lower adalimumab trough level in patients with elevated calprotectin.
authors: a Department of Gastroenterology , Royal Liverpool and Broadgreen University Hospital Trust , Liverpool , UK.
authors: Ashley
authors: A
authors: Bond
authors: b Department of Biostatistics , University of Liverpool , Liverpool , UK.
authors: Susanna
authors: S
authors: Dodd
authors: a Department of Gastroenterology , Royal Liverpool and Broadgreen University Hospital Trust , Liverpool , UK.
authors: Gareth
authors: G
authors: Fisher
authors: a Department of Gastroenterology , Royal Liverpool and Broadgreen University Hospital Trust , Liverpool , UK.
authors: Thomas
authors: T
authors: Skouras
authors: a Department of Gastroenterology , Royal Liverpool and Broadgreen University Hospital Trust , Liverpool , UK.
authors: Sreedhar
authors: S
authors: Subramanian
mesh_terms: D000068879:Adalimumab / Q000008:administration & dosage*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003131:Combined Modality Therapy; D003430:Cross-Sectional Studies; D016903:Drug Monitoring; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D006113:United Kingdom; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D007155:Immunologic Factors; D039841:Leukocyte L1 Antigen Complex; D000068879:Adalimumab
keywords: IBD-basic; IBD-clinical; immunology