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Efficacy and Safety of Belimumab and Azathioprine for Maintenance of Remission in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis: A Randomized Controlled Study
Author(s) -
Jayne David,
Blockmans Daniel,
Luqmani Raashid,
Moiseev Sergey,
Ji Beulah,
Green Yulia,
Hall Leanne,
Roth David,
Henderson Robert B.,
Merkel Peter A.
Publication year - 2019
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40802
Subject(s) - medicine , azathioprine , vasculitis , rituximab , population , microscopic polyangiitis , belimumab , clinical endpoint , cyclophosphamide , anti neutrophil cytoplasmic antibody , gastroenterology , randomized controlled trial , immunology , chemotherapy , antibody , disease , lymphoma , environmental health , b cell , b cell activating factor
Objective To evaluate the safety and efficacy of belimumab as adjunctive therapy to maintain remission in antineutrophil cytoplasmic antibody ( ANCA )–associated vasculitis ( AAV ). Methods In this multicenter, double‐blind, placebo‐controlled study, patients with AAV (ages ≥18 years) were randomized 1:1 to receive azathioprine (2 mg/kg/day), low‐dose oral glucocorticoids (≤10 mg/day), and either intravenous belimumab (10 mg/kg) or placebo, following remission induction with rituximab or cyclophosphamide along with glucocorticoids. The primary end point was time to first protocol‐specified event ( PSE ), with first PSE defined as a Birmingham Vasculitis Activity Score ( BVAS ) of ≥6, presence of ≥1 major BVAS item, or receipt of prohibited medications for any reason, resulting in treatment failure (adjusted for ANCA type [proteinase 3 ( PR 3) or myeloperoxidase ( MPO )], disease stage at induction, and induction regimen). Vasculitis relapse was defined as the PSE of either a BVAS activity score of ≥6 or receipt of prohibited medications for vasculitis. Changes in treatment practice led to truncation of the study population from ~300 patients to ~100 patients. Results The intent‐to‐treat population totaled 105 patients with AAV , of whom 52 (40 with PR 3‐ ANCA s, 12 with MPO ‐ ANCA s) received placebo and 53 (41 with PR 3‐ ANCA s, 12 with MPO ‐ ANCA s) received belimumab; 27 of the patients were in rituximab‐induced disease remission, while 78 were in cyclophosphamide‐induced disease remission at baseline. Compared with placebo, treatment with belimumab did not reduce the risk of a PSE (adjusted hazard ratio [ HR ] 1.07, 95% confidence interval [95% CI ] 0.44–2.59; P = 0.884) or vasculitis relapse (adjusted HR 0.88, 95% CI 0.29–2.65; P = 0.821). The overall rate of PSE s was low (11 [21.2%] of 52 patients receiving placebo, 10 [18.9%] of 53 patients receiving belimumab). Vasculitis relapse in the placebo group (n = 8) occurred independent of the induction regimen, disease stage, or ANCA type. All vasculitis relapses in the belimumab group (n = 6) occurred in patients who had PR 3‐ ANCA –associated vasculitis with cyclophosphamide‐induced disease remission. Adverse events occurred in 49 (92.5%) of 53 patients receiving belimumab and 43 (82.7%) of 52 patients receiving placebo, with no new safety concerns. Conclusion Belimumab plus azathioprine and glucocorticoids for the maintenance of remission in AAV did not reduce the risk of relapse.