Pegylated interferon-α-2b reduces corticosteroid requirement in patients with Behçet's disease with upregulation of circulating regulatory T cells and reduction of Th17

Ann Rheum Dis. 2015 Jun;74(6):1138-44. doi: 10.1136/annrheumdis-2014-205571. Epub 2014 Sep 30.

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.

Trial registration number: ISRCTN 36354474; EudraCT 2004-004301-18.

Keywords: Behcet's disease; Corticosteroids; DMARDs (biologic); T Cells.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage*
  • Adult
  • Antiviral Agents / therapeutic use*
  • Azathioprine / therapeutic use
  • Behcet Syndrome / drug therapy*
  • Behcet Syndrome / immunology
  • Cyclosporine / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / therapeutic use
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Lymphocyte Count
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / therapeutic use
  • Polyethylene Glycols / therapeutic use*
  • Quality of Life
  • Recombinant Proteins / therapeutic use
  • Single-Blind Method
  • Surveys and Questionnaires
  • T-Lymphocytes, Regulatory / cytology*
  • Tacrolimus / therapeutic use
  • Th17 Cells / cytology*
  • Treatment Outcome

Substances

  • Adrenal Cortex Hormones
  • Antiviral Agents
  • Immunosuppressive Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • Cyclosporine
  • peginterferon alfa-2b
  • Mycophenolic Acid
  • Azathioprine
  • Tacrolimus
  • Methotrexate

Associated data

  • EudraCT/2004-004301-18
  • ISRCTN/ISRCTN36354474