title: Serum Concentration of Anti-TNF Antibodies, Adverse Effects and Quality of Life in Patients with Inflammatory Bowel Disease in Remission on Maintenance Treatment.
abstract: OBJECTIVE
  High serum concentrations of infliximab [IFX] and adalimumab [ADA] may be associated with adverse effects in patients with inflammatory bowel disease [IBD]. We aimed to investigate whether high anti-tumour necrosis factor [TNF] trough levels [TLs] were associated with toxicity and impaired quality of life [QoL].
  
  
  METHODS
  We conducted a prospective cohort study in IBD patients in clinical and biochemical remission on IFX or ADA maintenance therapy. Trough serum concentrations and antidrug antibodies were measured in addition to biochemical markers of inflammation in serum and stool to confirm quiescent disease. QoL was assessed using the Inflammatory Bowel Disease Questionnaire and 36-item short form]. Side effects such as fatigue and arthralgia were measured with a visual analogue score [VAS]. Skin toxicity was reported with a European Organization for Research and Treatment of Cancer-derived score.
  
  
  RESULTS
  In all, 252 IBD patients on maintenance anti-TNF therapy were screened, of whom 95 [73 with Crohn's disease, 22 with ulcerative colitis; 72 on IFX, 23 on ADA] were in clinical and biochemical remission and were included. Median TLs were 5.5 µg/ml and 6.6 µg/ml for IFX and ADA, respectively. Patients with anti-TNF TLs above median had lower IBDQ scores than patients with lower TLs [IBDQ 176 vs 187, p = 0.02], particularly regarding systemic symptoms and emotional status. A trend towards lower SF-36 and higher fatigue scores was observed in the higher anti-TNF TL group. Skin and arthralgia scores were not significantly different between the groups.
  
  
  CONCLUSIONS
  IBD patients with higher anti-TNF serum concentrations had significantly lower disease-specific QoL. Fatigue, arthralgia, and skin lesions do not occur more often in these patients. These data are reassuring that high serum concentrations of anti-TNF antibodies are not toxic.
authors.affiliation: Inflammatory Bowel Disease Centre, Department of Gastroenterology & Hepatology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Johannan F
authors.initials: JF
authors.lastname: Brandse
authors.affiliation: Inflammatory Bowel Disease Centre, Department of Gastroenterology & Hepatology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Laura M C
authors.initials: LM
authors.lastname: Vos
authors.affiliation: Department of Gastroenterology & Hepatology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Jansen
authors.affiliation: Department of Gastroenterology & Hepatology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
authors.forename: Toos
authors.initials: T
authors.lastname: Schakel
authors.affiliation: Inflammatory Bowel Disease Centre, Department of Gastroenterology & Hepatology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Cyriel I J
authors.initials: CI
authors.lastname: Ponsioen
authors.affiliation: Inflammatory Bowel Disease Centre, Department of Gastroenterology & Hepatology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Gijs R
authors.initials: GR
authors.lastname: van den Brink
authors.affiliation: Inflammatory Bowel Disease Centre, Department of Gastroenterology & Hepatology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Geert R
authors.initials: GR
authors.lastname: D'Haens
authors.affiliation: Inflammatory Bowel Disease Centre, Department of Gastroenterology & Hepatology, Academic Medical Centre, Amsterdam, The Netherlands m.lowenberg@amc.uva.nl.
authors.forename: Mark
authors.initials: M
authors.lastname: Löwenberg
mesh_terms: D000068879:Adalimumab / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000069285:Infliximab / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D060046:Maintenance Chemotherapy / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000069285:Infliximab; D000068879:Adalimumab
keywords: Anti-TNF; inflammatory bowel disease; quality of life; side effects; trough levels