OP0205 Efficacy and safety evaluation of iguratimod, a novel anti-rheumatic agent – a double-blind, comparative study of iguratimod-MTX combination in rheumatoid arthritis patients with an inadequate response to MTX

Background Iguratimod is a novel small-molecule DMARD characterized by inhibitory effects on immunoglobulin production without suppression of proliferative response in B cells. Iguratimod also inhibits cytokine production by macrophages and synovial cells. It was shown that the rate of 20% improvement in ACR criteria (ACR20) with iguratimod was not inferior to that of salazosulfapyridine in Japanese rheumatoid arthritis (RA) patients (63.1% for iguratimod vs 57.7% for salazosulfapyridine). Different from iguratimod, the anti-inflammatory mechanism of MTX increased release of extracellular adenosine and decreased production of inflammatory mediators such as leukotriene B4 and collagenase. Iguratimod in combination with MTX is expected to have the synergistic effects for RA treatment. Objectives This study was conducted to evaluate the efficacy and safety of a combination therapy of iguratimod and MTX in Japanese RA patients with an inadequate response to MTX. Methods A placebo-controlled, double-blind, comparative study (24 weeks) was conducted in patients who had been treated with MTX at 6–8 mg per week for over 12 weeks. Iguratimod was orally administered in 165 patients at 25 mg/day for the first 4 weeks followed by 50 mg/day until Week 24. A matching placebo treatment was given to 88 patients. Upon completion of a comparative study (24 weeks) of iguratimod-MTX combination therapy, iguratimod + MTX Group (IM) continued the same regimen until Week 52 and placebo + MTX Group (PM) received iguratimod in substitution of placebo until Week 52. Folic acid was orally administered in all patients at 5 mg/week. Results ACR20 response rate at Week 24 was 69.5% (114/164) in IM and 30.7% (27/88) in PM, demonstrating superiority of IM to PM. ACR50 and ACR70 response rates were 38.4% and 17.1% in IM, 15.9% and 5.7% in PM respectively; therefore, the response rates in IM were statistically higher than those in PM. Incidence of adverse events was 80.5% in IM and 75.0% in PM and the difference was not statistically significant. Serious adverse events were reported by 5 patients in IM and 3 patients in PM.Response rates of ACR20, ACR50 and ACR70 in IM at Week 52 were 71.3%, 49.4% and 23.8%, respectively. Conclusions Iguratimod in combination with MTX is promising to become an alternate effective treatment for RA patients with an inadequate response to MTX. Disclosure of Interest M. Hara Consultant for: Toyama Chemical, N. Ishiguro Speakers Bureau: Abbott Japan, Astellas P