title: Pegylated interferon-α-2b reduces corticosteroid requirement in patients with Behçet's disease with upregulation of circulating regulatory T cells and reduction of Th17.
abstract: OBJECTIVE
  To determine whether the addition of 26 weeks of subcutaneous peginterferon-α-2b could reduce the requirement for systemic corticosteroids and conventional immunosuppressive medication in patients with Behçet's disease (BD).
  
  
  METHODS
  We conducted a multicentre randomised trial in patients with BD requiring systemic therapy. Patients were randomised to 26 weeks of peginterferon-α-2b in addition to their standard care or to standard care only and followed 6-monthly for 3 years with BD activity scores and quality of life questionnaires. Patients at one centre had blood taken to measure regulatory T cells (Tregs) and Th17 cells.
  
  
  RESULTS
  72 patients were included. At months 10-12, while among the entire patient population there was no difference in the corticosteroid dose or immunosuppression use between the treatment groups (adjusted OR 1.04, 95% CI 0.34 to 3.19), post hoc analysis revealed that in patients who were on corticosteroids at baseline the corticosteroid requirement was significantly lower in the peginterferon-α-2b (6.5 (5-15) mg/day) compared with the non-interferon group (10 (8.25-16.5) mg/day, p=0.039). Furthermore, there was a trend towards an improved quality of life that became significant by 36 months (p=0.008). This was associated with a significant rise in Tregs and a decrease in Th17 cells which was still present at 1 year and 6 months after the interferon was stopped. The safety profile was similar with adverse events in 10% in both groups.
  
  
  CONCLUSIONS
  The addition of peginterferon-α-2b to the drug regime of BD patients did not significantly reduce their corticosteroid dose required at 1 year. However, in those on corticosteroids at baseline post hoc analysis demonstrated that the addition of peginterferon-α-2b did result in a significant reduction in corticosteroid dose with a significantly improved quality of life and trend to reduce other required immunosuppressive agents. This effect was seen at 1 year and associated with a rise in Tregs suggesting a possible mode for interferon action.
  
  
  BACKGROUND
  ISRCTN 36354474; EudraCT 2004-004301-18.
authors.affiliation: Moorfields Eye Hospital NHS Foundation Trust, London, UK UCL Institute of Ophthalmology, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Lightman
authors.affiliation: Moorfields Eye Hospital NHS Foundation Trust, London, UK Imperial College Healthcare NHS Trust, London, UK.
authors.forename: S R J
authors.initials: SR
authors.lastname: Taylor
authors.affiliation: Moorfields Eye Hospital NHS Foundation Trust, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Bunce
authors.affiliation: Barts Health NHS Trust, London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Longhurst
authors.affiliation: Ealing Hospital NHS Trust, London, UK.
authors.forename: W
authors.initials: W
authors.lastname: Lynn
authors.affiliation: Aintree Hospitals NHS Trust, Liverpool, UK.
authors.forename: R
authors.initials: R
authors.lastname: Moots
authors.affiliation: GSTT NHS Foundation Trust, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Stanford
authors.affiliation: Moorfields Eye Hospital NHS Foundation Trust, London, UK UCL Institute of Ophthalmology, London, UK.
authors.forename: O
authors.initials: O
authors.lastname: Tomkins-Netzer
authors.affiliation: UCL Institute of Ophthalmology, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.affiliation: UCL Institute of Ophthalmology, London, UK.
authors.forename: V L
authors.initials: VL
authors.lastname: Calder
authors.affiliation: Imperial College Healthcare NHS Trust, London, UK.
authors.forename: D O
authors.initials: DO
authors.lastname: Haskard
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use; D001528:Behcet Syndrome / Q000188:drug therapy* / Q000276:immunology; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D018655:Lymphocyte Count; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011788:Quality of Life; D011994:Recombinant Proteins / Q000627:therapeutic use; D016037:Single-Blind Method; D011795:Surveys and Questionnaires; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D016559:Tacrolimus / Q000627:therapeutic use; D058504:Th17 Cells / Q000166:cytology*; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D016572:Cyclosporine; C417083:peginterferon alfa-2b; D009173:Mycophenolic Acid; D001379:Azathioprine; D016559:Tacrolimus; D008727:Methotrexate
keywords: Behcet's disease; Corticosteroids; DMARDs (biologic); T Cells