Alemtuzumab for refractory primary systemic vasculitis—a randomised controlled dose ranging clinical trial of efficacy and safety (ALEVIATE)

作者：Seerapani Gopaluni, Rona Smith, Goymer Donna, Hugh Cahill, Elizabeth Broadhurst, Elizabeth Wallin, Mark McClure, Afzal Chaudhry, David Jayne · 发表于：Arthritis Research & Therapy · 年份：2022 · DOI：10.1186/s13075-022-02761-6 · 被引用次数：30 · 研究领域：Vasculitis and related conditions、Ocular Diseases and Behçet’s Syndrome、Otitis Media and Relapsing Polychondritis

BACKGROUND: Primary systemic vasculitis (PSV) is a heterogeneous group of autoimmune conditions. There is an unmet need for alternative therapies that lead to sustained remission in patients with refractory disease. Alemtuzumab, an anti-CD52 antibody, depletes lymphocytes for prolonged periods and, in retrospective studies, has induced sustained, treatment-free remissions in patients with refractory/relapsing vasculitis but has raised safety concerns of infection and secondary autoimmunity. This phase IIb clinical trial aimed to assess the efficacy and safety of alemtuzumab, at two different doses, in inducing remission in refractory vasculitis patients. METHODS: The ALEVIATE trial was a randomised, prospective, open-label, dose ranging clinical trial. Patients with refractory ANCA-associated vasculitis (AAV) or Behçet's disease (BD) were randomised to receive either 60 mg or 30 mg alemtuzumab. Treatments were administered at baseline and 6 months or earlier where clinically appropriate. A maximum of three treatments were allowed within the 12-month study period. RESULTS: Twenty-three patients received at least one dose of alemtuzumab. Twelve had AAV, and 11 a diagnosis of BD. The median age was 40 years (range 28-44), with a prior disease duration of 61 months (42-103). Sixteen (70%) achieved either complete (6/23, 26%) or partial (10/23, 44%) response at 6 months. Eight (35%) maintained remission to the end of the trial without relapse. Ten severe adverse events were observ...