Posted by on Feb 5, 2023 in Rheumatoid Arthritis | 0 comments

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

Original Title :

Safety and efficacy of the miR-124 upregulator ABX464 (obefazimod, 50 and 100 mg per day) in patients with active rheumatoid arthritis and inadequate response to methotrexate and/or anti-TNFα therapy: a placebo-controlled phase II study.

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