title: Increased pretreatment serum IFN-β/α ratio predicts non-response to tumour necrosis factor α inhibition in rheumatoid arthritis.
abstract: Studies suggest that circulating type I interferon (IFN) may predict response to biological agents in rheumatoid arthritis (RA). Prediction of response prior to initiating therapy would represent a major advancement.
  
  
  
  We studied sera from a test set of 32 patients with RA from the Auto-immune Biomarkers Collaborative Network Consortium and a validation set of 92 patients with RA from the Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository registry. The test set included those with good response or no response to tumour necrosis factor (TNF) inhibitors at 14 weeks by European League Against Rheumatism criteria. The validation set included subjects with good, moderate or no response at 12 weeks. Total serum type I IFN activity, IFN-α and IFN-β activity were measured using a functional reporter cell assay.
  
  
  
  In the test set, an increased ratio of IFN-β to IFN-α (IFN-β/α activity ratio) in pretreatment serum associated with lack of response to TNF inhibition (p=0.013). Anti-cyclic citrullinated peptide antibody titre and class of TNF inhibitor did not influence this relationship. A receiver-operator curve supported a ratio of 1.3 as the optimal cut-off. In the validation set, subjects with an IFN-β/α activity ratio >1.3 were significantly more likely to have non-response than good response (OR=6.67, p=0.018). The test had 77% specificity and 45% sensitivity for prediction of non-response compared with moderate or good response. Meta-analysis of test and validation sets confirmed strong predictive capacity of IFN-β/α activity ratio (p=0.005).
  
  
  
  Increased pretreatment serum IFN-β/α ratio strongly associated with non-response to TNF inhibition. This study supports further investigation of serum type I IFN in predicting outcome of TNF inhibition in RA.
authors.affiliation: Division of Rheumatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Theresa
authors.initials: T
authors.lastname: Wampler Muskardin
authors.affiliation: Division of Rheumatology, University of Nebraska Medical Center, Omaha, USA.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Vashisht
authors.affiliation: Division of Rheumatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Dorschner
authors.affiliation: Division of Rheumatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jensen
authors.affiliation: Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois, USA.
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Chrabot
authors.affiliation: Center for Genomics and Human Genetics, Feinstein Institute Medical Research, North Shore LIJ Health System, New York, New York, USA.
authors.forename: Marlena
authors.initials: M
authors.lastname: Kern
authors.affiliation: Division of Clinical Immunology and Rheumatology, University of Alabama, Birmingham, Alabama, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Curtis
authors.affiliation: Division of Clinical Immunology and Rheumatology, University of Alabama, Birmingham, Alabama, USA.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Danila
authors.affiliation: Division of Clinical Immunology and Rheumatology, University of Alabama, Birmingham, Alabama, USA.
authors.forename: Stacey S
authors.initials: SS
authors.lastname: Cofield
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Shadick
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Nigrovic
authors.affiliation: Division of Rheumatology and Immunology, Duke University, Durham, USA.
authors.forename: E William
authors.initials: EW
authors.lastname: St Clair
authors.affiliation: Divisions of Rheumatology and Allergy, Johns Hopkins University, Baltimore, USA.
authors.forename: Clifton O
authors.initials: CO
authors.lastname: Bingham
authors.affiliation: Division of Rheumatology and Allergy-Clinical Immunology, North Shore-LIJ Health System, Lake success, New York, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Furie
authors.affiliation: Division of Immunology and Rheumatology, Stanford University, Stanford, California, USA.
authors.forename: William
authors.initials: W
authors.lastname: Robinson
authors.affiliation: Division of Immunology and Rheumatology, Stanford University, Stanford, California, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Genovese
authors.affiliation: Division of Rheumatology, University of Colorado Denver, Denver, USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Striebich
authors.affiliation: Division of Rheumatology, University of Nebraska Medical Center, Omaha, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: O'Dell
authors.affiliation: Division of Rheumatology, University of Nebraska Medical Center, Omaha, USA.
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Thiele
authors.affiliation: Division of Rheumatology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Larry W
authors.initials: LW
authors.lastname: Moreland
authors.affiliation: Division of Rheumatology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Levesque
authors.affiliation: Division of Clinical Immunology and Rheumatology, University of Alabama, Birmingham, Alabama, USA.
authors.forename: S Louis
authors.initials: SL
authors.lastname: Bridges
authors.affiliation: Center for Genomics and Human Genetics, Feinstein Institute Medical Research, North Shore LIJ Health System, New York, New York, USA.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
authors.affiliation: Division of Rheumatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Timothy B
authors.identifier: 0000-0003-3532-6660
authors.initials: TB
authors.lastname: Niewold
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D016208:Databases, Factual; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000097:blood*; D016899:Interferon-beta / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012042:Registries; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D016898:Interferon-alpha; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta
keywords: Cytokines; Rheumatoid Arthritis; TNF-alpha; Treatment