Pegylated interferon-alpha-2b reduces corticosteroid requirement in patients with Behcet's disease with upregulation of circulating regulatory T cells and reduction of Th17
File(s)
Accepted version
Author(s)
Type
Journal Article
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.
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.
Date Issued
2015-06-01
Date Acceptance
2014-09-13
Citation
Annals of the Rheumatic Diseases, 2015, 74 (6), pp.1138-1144
ISSN
0003-4967
Publisher
BMJ Publishing Group
Start Page
1138
End Page
1144
Journal / Book Title
Annals of the Rheumatic Diseases
Volume
74
Issue
6
Copyright Statement
© Article author (or their employer) 2014. Produced by BMJ Publishing Group Ltd (& EULAR) under licence.
Sponsor
National Institute for Health Research
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000354371200028&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
CDF-2011-04-051
Subjects
Science & Technology
Life Sciences & Biomedicine
Rheumatology
Behcet's disease
DMARDs (biologic)
Corticosteroids
T Cells
TNF-ALPHA THERAPY
RHEUMATOID-ARTHRITIS
PROSPECTIVE TRIAL
TREG-CELLS
UVEITIS
INFLIXIMAB
EFFICACY
DIFFERENTIATION
AZATHIOPRINE
CYCLOSPORINE
Publication Status
Published
Date Publish Online
2014-09-30