PMID- 33658052
OWN - NLM
STAT- MEDLINE
DCOM- 20210621
LR  - 20210621
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 23
IP  - 1
DP  - 2021 Mar 3
TI  - Safety and efficacy of low-dose intravenous arsenic trioxide in systemic lupus 
      erythematosus: an open-label phase IIa trial (Lupsenic).
PG  - 70
LID - 10.1186/s13075-021-02454-6 [doi]
LID - 70
AB  - 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 < 0.01). In the long term, 6 
      patients attained LLDAS at W52, which continued at last follow-up (median LLDAS 
      duration 3 years, range 2-4). CONCLUSIONS: A short course of ATO has an 
      acceptable safety profile in SLE patients and encouraging efficacy. TRIAL 
      REGISTRATION: ClinicalTrials.gov, NCT01738360  registered 30 November 2012.
FAU - Hamidou, Mohamed
AU  - Hamidou M
AD  - Department of Internal Medicine, CHU Nantes, Nantes Universite, Nantes, France. 
      mohamed.hamidou@chu-nantes.fr.
FAU - Neel, Antoine
AU  - Neel A
AD  - Department of Internal Medicine, CHU Nantes, Nantes Universite, Nantes, France.
FAU - Poupon, Joel
AU  - Poupon J
AD  - Department of Biological Toxicology, AP-HP, Lariboisiere Hospital, University 
      Paris VII, Paris, France.
FAU - Amoura, Zahir
AU  - Amoura Z
AD  - Department of Internal Medicine 2, Centre National de Reference pour le Lupus, 
      Institut E3M, Hopital Pitie-Salpetriere, Paris, France.
FAU - Ebbo, Mikael
AU  - Ebbo M
AD  - Service de Medecine Interne, Aix Marseille Univ, APHM, CNRS, INSERM, CIML, 
      Hopital de la Timone, Marseille, France.
FAU - Sibilia, Jean
AU  - Sibilia J
AD  - Department of Rheumatology, University of Strasbourg, Strasbourg, France.
FAU - Viallard, Jean-Francois
AU  - Viallard JF
AD  - Department of Internal Medicine, Haut-Leveque University Hospital, Bordeaux, 
      France.
FAU - Gaborit, Benjamin
AU  - Gaborit B
AD  - Department of Internal Medicine, CHU Nantes, Nantes Universite, Nantes, France.
FAU - Volteau, Christelle
AU  - Volteau C
AD  - Plateforme de Methodologie et Biostatistiques, CHU Nantes, Universite de Nantes, 
      Nantes, France.
FAU - Hardouin, Jean Benoit
AU  - Hardouin JB
AD  - INSERM UMR 1246-SPHERE, Universite de Nantes, Nantes, France.
FAU - Hachulla, Eric
AU  - Hachulla E
AD  - Department of Internal Medicine, Centre de Reference des Maladies Autoimmunes 
      Systemiques Rares du Nord et Nord-Ouest de France (CeRAINO), University of Lille, 
      Lille, France.
FAU - Rieger, Francois
AU  - Rieger F
AD  - MEDSENIC, SAS, a company with CNRS participation, Strasbourg, France.
LA  - eng
SI  - ClinicalTrials.gov/NCT01738360
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210303
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Immunosuppressive Agents)
RN  - S7V92P67HO (Arsenic Trioxide)
SB  - IM
MH  - Adult
MH  - *Antibodies, Monoclonal, Humanized
MH  - Arsenic Trioxide
MH  - Humans
MH  - Immunosuppressive Agents
MH  - *Lupus Erythematosus, Systemic/drug therapy
MH  - Severity of Illness Index
MH  - Treatment Outcome
PMC - PMC7927234
OTO - NOTNLM
OT  - Arsenic trioxide
OT  - Autoimmune diseases
OT  - Phase II clinical trial
OT  - Systemic lupus erythematosus
OT  - Treatment
COIS- Francois Rieger is currently an employee of MEDSENIC.
EDAT- 2021/03/05 06:00
MHDA- 2021/06/22 06:00
PMCR- 2021/03/03
CRDT- 2021/03/04 05:34
PHST- 2020/04/17 00:00 [received]
PHST- 2021/02/18 00:00 [accepted]
PHST- 2021/03/04 05:34 [entrez]
PHST- 2021/03/05 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2021/03/03 00:00 [pmc-release]
AID - 10.1186/s13075-021-02454-6 [pii]
AID - 2454 [pii]
AID - 10.1186/s13075-021-02454-6 [doi]
PST - epublish
SO  - Arthritis Res Ther. 2021 Mar 3;23(1):70. doi: 10.1186/s13075-021-02454-6.