title: True infliximab resistance in rheumatoid arthritis: a role for lymphotoxin alpha?
abstract: BACKGROUND
  The combination of methotrexate and the anti-tumour necrosis factor alpha (TNFalpha) antibody infliximab is a very effective treatment for rheumatoid arthritis (RA). However, a proportion of patients are not responsive to this treatment. Inefficacy may represent a TNFalpha independent disease or insufficient drug at the site of action.
  
  
  METHODS
  A patient with RA resistant to repeated high dose infliximab infusions and intra-articular infliximab into an inflamed knee is described. No beneficial clinical effect was observed. Pre-injection arthroscopic biopsy of the study knee demonstrated TNFalpha staining but also confirmed the presence of lymphotoxin alpha (LTalpha or TNFbeta) on immunohistochemistry. Subsequent treatment with etanercept (which blocks LTalpha as well as TNFalpha) resulted in clinical remission of disease.
  
  
  CONCLUSIONS
  This case suggests that resistance to TNF blockade may occur when TNFalpha is not the dominant inflammatory cytokine and suggests that LTalpha may have a pathogenic role in RA.
authors.affiliation: Academic Unit of Musculoskeletal Disease, 1st Floor, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK.
authors.forename: M H
authors.initials: MH
authors.lastname: Buch
authors.forename: P G
authors.initials: PG
authors.lastname: Conaghan
authors.forename: M A
authors.initials: MA
authors.lastname: Quinn
authors.forename: S J
authors.initials: SJ
authors.lastname: Bingham
authors.forename: D
authors.initials: D
authors.lastname: Veale
authors.forename: P
authors.initials: P
authors.lastname: Emery
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D004351:Drug Resistance; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D008233:Lymphotoxin-alpha / Q000037:antagonists & inhibitors / Q000502:physiology*; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D008233:Lymphotoxin-alpha; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept