In a nutshell
This study investigated the safety and effectiveness of ABX464 (Obefazimod) in patients with active rheumatoid arthritis (RA) with inadequate responses to methotrexate (Trexall) or anti-tumor necrosis factor alpha (anti-TNFα) treatment. The authors concluded that ABX464 was safe and well-tolerated with promising effectiveness in these patients at a daily dose of 50 mg.
Some background
RA is a progressive, inflammatory disease that causes joint damage, disabilities, and reduced quality of life. First line therapy for RA usually involves the use of conventional disease-modifying anti-rheumatic drugs (cDMARDS) such as methotrexate (MTX). If treatment responses are inadequate, a biological DMARD like anti-TNFα or a targeted synthetic DMARD may be added.
ABX464 regulates the production of micro-RNA-124 (miR-124). miR-124 is a biological molecule that has been implicated in inflammation. The anti-inflammatory effects of ABX464 had been recognized in the treatment of ulcerative colitis (UC; a bowel inflammatory disease) for patients. Based on this, there is a need to investigate potential uses of ABX464 in patients with active RA that have had inadequate responses to first line therapy.
Methods & findings
This study included 60 patients with active RA. Patients were randomly assigned to 3 groups. Group 1 included 21 patients who received 50 mg of daily, orally-administered ABX464. Group 2 included 19 patients who were given oral ABX464 at a daily dose of 100 mg. Group 3 included 20 patients who received a daily, orally administered placebo. Patients were evaluated for safety, ACR 20 and ACR 50 responses, and disease activity over 12 weeks. ACR 20 means a 20% improvement in RA symptoms and signs. ACR 50 means a 50% improvement in RA symptoms and signs.
More patients in groups 1 (85.7%) and 2 (94.7%) experienced side effects compared to group 3 (70%). Mild-to-moderate treatment side effects such as upper abdominal pain, diarrhea, vomiting, and headache were higher in group 2. Serious side effects were slightly more common in groups 1 (14.3%) and 2 (15.8%) compared to group 3 (5%).
After 8 weeks, disease activity was significantly decreased in groups 1 and 2 compared to the placebo group. Slightly more patients in group 2 achieved ACR 20 and ACR 50 compared to placebo.
The bottom line
The study showed that 50 mg of ABX464 was safe and well-tolerated in patients with RA unresponsive to standard treatments.
The fine print
The study included a very small number of patients. Larger scale studies are needed for more definitive conclusions to be drawn. This study was funded by Abivax, the manufacturer of ABX464.
Published By :
Annals of the rheumatic diseases
Date :
May 31, 2022
