Extended versus standard azathioprine maintenance therapy in newly diagnosed proteinase-3 anti-neutrophil cytoplasmic antibody-associated vasculitis patients who remain cytoplasmic anti-neutrophil cytoplasmic antibody-positive after induction of remission: a randomized clinical trial

• Published in: Nephrology, dialysis, transplantation Vol. 31; no. 9; pp. 1453 - 1459
• Main Authors: Sanders, Jan-Stephan F, de Joode, Anoek A E, DeSevaux, Ruud G, Broekroelofs, Jan, Voskuyl, Alexandre E, van Paassen, Pieter, Kallenberg, Cees G M, Tervaert, Jan Willem Cohen, Stegeman, Coen A
• Format: Journal Article
• Language: English
• Published: England 01.09.2016
• Subjects: Adrenal Cortex Hormones - therapeutic use; Adult; Aged; Aged, 80 and over; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - drug therapy; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - epidemiology; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - immunology; Antibodies, Antineutrophil Cytoplasmic - immunology; Azathioprine - therapeutic use; Cyclophosphamide - therapeutic use; Female; Humans; Immunosuppressive Agents - therapeutic use; Incidence; Male; Middle Aged; Myeloblastin - immunology; Netherlands - epidemiology; Recurrence; Remission Induction; Standard of Care; Young Adult; maintenance therapy; proteinase 3; ANCA; relapse; vasculitis
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfw211

Cytoplasmic anti-neutrophil cytoplasmic antibody (C-ANCA) positivity at remission has been associated with an increased relapse rate in patients with proteinase 3 anti-neutrophil cytoplasmic antibody-associated vasculitis (PR3-AAV) after a switch to azathioprine maintenance therapy. We therefore hypothesized that extended azathioprine maintenance therapy could reduce the incidence of relapse in this setting. Patients newly diagnosed with PR3-AAV at 12 centres in The Netherlands during 2003-11 who received a standardized induction regimen consisting of oral cyclophosphamide and corticosteroids were enrolled (n = 131). Patients were randomized to standard or extended azathioprine maintenance therapy when C-ANCA was positive at the time of stable remission. Standard maintenance treatment consisted of azathioprine (1.5-2.0 mg/kg) until 1 year after diagnosis and subsequent tapering to 25 mg every 3 months. Extended azathioprine maintenance therapy (1.5-2.0 mg/kg) was continued until 4 years after diagnosis and tapered thereafter. The primary endpoint was relapse-free survival at 4 years after diagnosis. In patients with PR3-AAV who were C-ANCA positive at the time of stable remission, relapse-free survival at 4 years after diagnosis did not differ significantly between standard azathioprine (n = 24) and extended azathioprine (n = 21) maintenance therapy (P = 0.40). There was also no significant difference in relapse-free survival between patients receiving standard azathioprine (n = 106) versus extended azathioprine maintenance therapy (n = 21; P = 0.94). In addition, there was no difference in the relapse rate between patients with PR3-AAV who were C-ANCA positive (n = 45) at the time of remission versus patients who became C-ANCA negative at the time of remission (n = 82; P = 0.62). This randomized trial suggests that extended azathioprine maintenance therapy has only a limited effect on the prevention of relapse in patients with PR3-AAV at 4 years after diagnosis. Moreover, positive C-ANCA status at stable remission was not associated with an increased rate of relapse. ClinicalTrials.gov NCT 00128895.