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

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

Evaluation of Vitamin D Status in Rheumatoid Arthritis and Its Association with Disease Activity across 15 Countries: “The COMORA Study”

The aims of this study are to evaluate vitamin D status in 1413 RA patients of COMORA study from 15 countries and to analyze relationship between patients’ RA characteristics and low levels of vitamin D. All demographic, clinical, and biological data and RA comorbidities were completed. The results showed that the average of vitamin D serum dosage was 27.3 ng/mL ± 15.1 [0.1–151]. Status of vitamin D was insufficient in 54.6% and deficient in 8.5% of patients. 43% of RA patients were supplemented with vitamin D and absence of supplementation on vitamin D was related to higher prevalence of vitamin D deficiency (p<0.001). Finally, our study shows that the status of low levels of vitamin D is common in RA in different countries and under different latitudes. Absence of supplementation on vitamin D was related to higher prevalence of vitamin D deficiency. Low levels of vitamin D were associated with patients characteristics (age, BMI, and educational level), RA (disease activity and corticosteroid dosage), and comorbidities (lung disease and osteoporosis therapy). This suggests the need for a particular therapeutic strategy to improve vitamin D status in RA patients.