Safety and efficacy of low-dose intravenous arsenic trioxide in systemic lupus erythematosus: an open-label phase IIa trial (Lupsenic).

ABSTRACT:

Background

Lupus animal model has shown that arsenic trioxide (ATO), a treatment of acute promyelocytic leukaemia, could be effective in SLE. This is the first clinical study to determine the safety and efficacy of a short course of intravenous ATO in patients with active SLE.

Methods

This phase IIa, open-label, dose-escalating study enrolled 11 adult SLE patients with a non-organ threatening disease, clinically active despite conventional therapy. Patients received 10 IV infusions of ATO within 24?days. The first group received 0.10?mg/kg per injection, with dose-escalating to 0.15?mg/kg in a second group, and to 0.20?mg/kg in a third group. The primary endpoint was the occurrence of adverse events (AEs) and secondary endpoints were the number of SLE Responder Index 4 (SRI-4) responders at week 24 and reduction of corticosteroid dosage. In an exploratory analysis, we collected long-term data for safety and attainment of lupus low disease activity state (LLDAS).

Results

Four serious AEs occurred (grade 3 neutropenia, osteitis, neuropathy), 2 of which were attributable to ATO (neutropenia in the 2 patients treated with mycophenolate). Two patients suffered a severe flare during the last 4?weeks of the trial. At W24, five patients among 10 were SRI-4 responders. Overall, mean corticosteroid dosage decreased from 11.25?mg/day at baseline to 6?mg/day at W24 (P?ConclusionsA short course of ATO has an acceptable safety profile in SLE patients and encouraging efficacy.

Trial registration

ClinicalTrials.gov, NCT01738360  registered 30 November 2012.

SUBMITTER: Hamidou M 

PROVIDER: S-EPMC7927234 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature