title: Patients with RA in remission on TNF blockers: when and in whom can TNF blocker therapy be stopped?
abstract: OBJECTIVE
  Combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockade has increased remission rates in patients with rheumatoid arthritis. However, there are no guidelines regarding cessation of therapy. There is a need for markers predictive of sustained remission following cessation of TNF blocker therapy.
  
  
  METHODS
  Patients in remission (DAS28 <2.6) treated with a TNF blocker and MTX as initial or delayed therapy were recruited. Joints were assessed for grey scale synovitis and power Doppler (PD) activity. Immunological assessment involved advanced six-colour flow cytometry.
  
  
  RESULTS
  Of the 47 patients recruited, 27 had received initial treatment and 20 delayed treatment with TNF blocking drugs. Two years after stopping TNF blocker therapy, the main predictor of successful cessation was timing of treatment; 59% of patients in the initial treatment group sustained remission compared with 15% in the delayed treatment group (p=0.003). Within the initial treatment group, secondary analysis showed that the only clinical predictor of successful cessation of treatment was shorter symptom duration before receiving treatment (median 5.5 months vs 9 months; p=0.008). No other clinical features were associated with successful cessation of therapy. Thirty-five per cent of patients had low PD activity but levels were not informative. Several immunological parameters were significantly associated with sustained remission including abnormal differentiation subset of T cells and regulatory T cells. Similar non-significant trends were observed in the delayed treatment group.
  
  
  CONCLUSIONS
  In patients in remission with low levels of imaging synovitis receiving combination treatment with a TNF blocker and MTX, immunological parameters and short duration of untreated symptoms were associated with successful cessation of TNF blocker therapy.
authors.affiliation: Leeds Institute of Molecular Medicine, University of Leeds, Chapel Allerton Hospital, Chapeltown Road, Leeds, UK.
authors.forename: Benazir
authors.initials: B
authors.lastname: Saleem
authors.forename: Helen
authors.initials: H
authors.lastname: Keen
authors.forename: Vincent
authors.initials: V
authors.lastname: Goeb
authors.forename: Rekha
authors.initials: R
authors.lastname: Parmar
authors.forename: Sharmin
authors.initials: S
authors.lastname: Nizam
authors.forename: Elizabeth M A
authors.initials: EM
authors.lastname: Hensor
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Churchman
authors.forename: Mark
authors.initials: M
authors.lastname: Quinn
authors.forename: Richard
authors.initials: R
authors.lastname: Wakefield
authors.forename: Philip G
authors.initials: PG
authors.lastname: Conaghan
authors.forename: Frederique
authors.initials: F
authors.lastname: Ponchel
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D012074:Remission Induction; D013585:Synovitis / Q000000981:diagnostic imaging / Q000209:etiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate