title: A Systematic Review on Infliximab and Adalimumab Drug Monitoring: Levels, Clinical Outcomes and Assays.
abstract: Immunogenicity to therapeutic proteins has been linked to loss of response by a large percentage of patients taking anti-tumor necrosis factor-alpha agents. Drug monitoring can be extremely useful, allowing physicians to adjust the therapeutic scheme individually. This article aims to systematically review the published data with respect to cutoff levels of infliximab (IFX) and adalimumab (ADA) and relate them to the methodology adopted for quantification of IFX and ADA levels and clinical outcomes.
  
  
  
  The PubMed database was searched to identify studies focusing on the association between IFX or ADA cutoff levels and clinical outcomes in patients with inflammatory bowel disease.
  
  
  
  Of the 1654 articles initially selected by queries, 20 were included. A receiver operating characteristic curve analysis was performed to identify cutoff levels of IFX or ADA that correlated with a clinical outcome, but only 6 studies performed the same analysis for antidrug antibody levels. Cutoff levels were different between studies. The methodology chosen for level quantifications, clinical outcomes, and sample size and characteristics were also different. Nevertheless, measurement of drug levels should be performed during maintenance, and with loss of response, with persistent high levels of C-reactive protein, and when mucosal lesions are still present. In these scenarios, drug and antidrug levels were correlated with clinical outcomes.
  
  
  
  Concerning drug levels monitoring any methodology is adequate. With respect to antidrug antibody levels, it will be necessary to define a gold standard method or to establish different cutoff levels for different methodologies.
authors: *Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal; †MedInUP, Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal;and ‡Departments of Internal Medicine, and §Gastroenterology, Faculty of Medicine, Centro Hospitalar S. João, Porto, Portugal.
authors: Filipa
authors: F
authors: Silva-Ferreira
authors: Joana
authors: J
authors: Afonso
authors: Pedro
authors: P
authors: Pinto-Lopes
authors: Fernando
authors: F
authors: Magro
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D016903:Drug Monitoring; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D000069285:Infliximab / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000069285:Infliximab; D000068879:Adalimumab