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

Lightman, S, Taylor, SR, Bunce, C, Longhurst, H, Lynn, W, Moots, R, Stanford, M, Tomkins-Netzer, O, Yang, D, Calder, VL and Haskard, DO (2015) Pegylated interferon-α-2b reduces corticosteroid requirement in patients with Behcet's disease with upregulation of circulating regulatory T cells and reduction of Th17. Annals of the rheumatic diseases, 74 (6). pp. 1138-1144.

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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.

Item Type: Article
Authors :
NameEmailORCID
Lightman, SUNSPECIFIEDUNSPECIFIED
Taylor, SRs.r.taylor@surrey.ac.ukUNSPECIFIED
Bunce, CUNSPECIFIEDUNSPECIFIED
Longhurst, HUNSPECIFIEDUNSPECIFIED
Lynn, WUNSPECIFIEDUNSPECIFIED
Moots, RUNSPECIFIEDUNSPECIFIED
Stanford, MUNSPECIFIEDUNSPECIFIED
Tomkins-Netzer, OUNSPECIFIEDUNSPECIFIED
Yang, DUNSPECIFIEDUNSPECIFIED
Calder, VLUNSPECIFIEDUNSPECIFIED
Haskard, DOUNSPECIFIEDUNSPECIFIED
Date : June 2015
Identification Number : https://doi.org/10.1136/annrheumdis-2014-205571
Uncontrolled Keywords : Humans, Behcet Syndrome, Polyethylene Glycols, Mycophenolic Acid, Tacrolimus, Methotrexate, Azathioprine, Cyclosporine, Adrenal Cortex Hormones, Interferon-alpha, Recombinant Proteins, Immunosuppressive Agents, Antiviral Agents, Lymphocyte Count, Treatment Outcome, Drug Therapy, Combination, Questionnaires, Single-Blind Method, Quality of Life, Adult, Middle Aged, Female, Male, T-Lymphocytes, Regulatory, Th17 Cells
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:41
Last Modified : 17 May 2017 14:51
URI: http://epubs.surrey.ac.uk/id/eprint/828809

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