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

Seerapani Gopaluni, Rona Smith, Donna Goymer, Hugh Cahill, Elizabeth Broadhurst, Elizabeth Wallin, Mark McClure, Afzal Chaudhry, David Jayne, Seerapani Gopaluni, Rona Smith, Donna Goymer, Hugh Cahill, Elizabeth Broadhurst, Elizabeth Wallin, Mark McClure, Afzal Chaudhry, David Jayne

Abstract

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 observed in 7 (30%) patients; 4 were related to alemtuzumab. There were no differences in clinical endpoints between the 60 and 30 mg alemtuzumab treatment groups.

Conclusion: In a selected group of refractory vasculitis patients, alemtuzumab led to remission in two thirds of patients at 6 months. Remission was maintained to 12 months in a third of the patients, and the safety profile was acceptable.

Trial registration: ClinicalTrials.gov identifier: NCT01405807, EudraCT Number: 2009-017087-17. Registered on April 07, 2011.

Keywords: ANCA; Alemtuzumab; Behçet’s disease; Clinical trial; Lymphocytes; T cells; Vasculitis.

Conflict of interest statement

DJ has received research grants from Chemocentryx, GSK, Roche/Genentech and Sanofi-Genzyme and consultancy fees from Astra-Zeneca, Boehringer-Ingelheim, Chemocentryx, Chugai, GSK, Infla-RX, Insmed and Takeda. RS has received lecture fess from Roche and consultancy fees from GSK and Nordic Pharma. SG, DG, HC, EB, EW, MM, AC none.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
BVAS/WG items scored at randomisation
Fig. 2
Fig. 2
Proportion of patients with different organ system involvement at the time of recruitment into the trial
Fig. 3
Fig. 3
a Boxplot showing median and IQR of BVAS/WG scores at entry, 6 months and 12 moths. b Boxplot showing of oral prednisolone dose (in mg) at baseline, 6 months and 12 months
Fig. 4
Fig. 4
Individual response to therapy for each patient at each visit during the trial
Fig. 5
Fig. 5
Absolute counts (1 × 109/L) of CD4, CD8 and CD19 subsets tracked over the course of the trial. Plots represent median, lower and upper quartiles

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