title: Personalized biological treatment for rheumatoid arthritis: a systematic review with a focus on clinical applicability.
abstract: OBJECTIVE
  To review studies that address prediction of response to biologic treatment in RA and to explore the clinical utility of the studied (bio)markers.
  
  
  METHODS
  A search for relevant articles was performed in PubMed, Embase and Cochrane databases. Studies that presented predictive values or in which these could be calculated were selected. The added value was determined by the added value on prior probability for each (bio)marker. Only an increase/decrease in chance of response ⩾15% was considered clinically relevant, whereas in oncology values >25% are common.
  
  
  RESULTS
  Of the 57 eligible studies, 14 (bio)markers were studied in more than one cohort and an overview of the added predictive value of each marker is presented. Of the replicated predictors, none consistently showed an increase/decrease in probability of response ⩾15%. However, positivity of RF and ACPA in case of rituximab and the presence of the TNF-α promoter 308 GG genotype for TNF inhibitor therapy were consistently predictive, yet low in added predictive value. Besides these, 65 (bio)markers studied once showed remarkably high (but not validated) predictive values.
  
  
  CONCLUSIONS
  We were unable to address clinically useful baseline (bio)markers for use in individually tailored treatment. Some predictors are consistently predictive, yet low in added predictive value, while several others are promising but await replication. The challenge now is to design studies to validate all explored and promising findings individually and in combination to make these (bio)markers relevant to clinical practice.
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands b.v.j.cuppen@umcutrecht.nl.
authors.forename: Bart V J
authors.initials: BV
authors.lastname: Cuppen
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Paco M J
authors.initials: PM
authors.lastname: Welsing
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Sprengers
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Johannes W J
authors.initials: JW
authors.lastname: Bijlsma
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Anne C A
authors.initials: AC
authors.lastname: Marijnissen
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: van Laar
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Floris P J G
authors.initials: FP
authors.lastname: Lafeber
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Sandhya C
authors.initials: SC
authors.lastname: Nair
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D001688:Biological Products / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D057285:Precision Medicine / Q000379:methods; D011237:Predictive Value of Tests
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D015415:Biomarkers
keywords: ACR; EULAR; TNF inhibitors; abatacept; anakinra; biologics; biomarkers; markers; prediction; response; rheumatoid arthritis; rituximab; tocilizumab; treatment