Have you ever heard of Iguratimod (IGU)? It is a conventional synthetic DMARD that was developed in Japan and has been used for the treatment of rheumatoid arthritis in Asia since 2003!
It was initially developed as an anti-inflammatory medication, but was subsequently found to have disease modifying effects in type II collagen induced mice models. It works by inhibiting B cells and NF-kB, with downstream decreased production of IL-6, IL-8 and TNF-alpha. It also has a direct effect on MMPs and has been shown to protect against cartilage destruction and bone erosion in animal models.
In 2013, Jiantou Li et al. published a systematic review of four published RCTs, two from China and two from Japan, in a total of 1407 RA patients, showing similar efficacy as SSZ and MTX. Ishiguro et al. in 2013 showed that the combination of MTX and IGU was superior to MTX monotherapy.
At EULAR 2017, a group from Japan showed long-term, real-world data on 120 RA patients treated with IGU from April 2013 to July 2016. The study population had a mean age of 64 years, mean disease duration of 10 years, 87% were RF positive, 85% were ACPA positive and the majority had failed at least two previous DMARDs. 60% received concomitant MTX with a mean dose of 5 mg/wk. The reasons for using IGU (instead of biologics) included intolerance to MTX, old age (over 80), low socioeconomic status (unable to afford biologics), chronic infection, interstitial pneumonia, chronic renal failure, severe lung disease, and previous or active malignancy. Retention rates on IGU were 70% at 1 year and 43% at 3 years. 60% of patients stopped due to adverse events and 23% for lack of efficacy. Fifteen patients achieved DAS28 remission at 2 years.
In another poster from Japan, administrative data was used to compare patients receiving the combination of IGU-MTX (n=66) and those receiving SSZ-MTX (n=163) for RA from April 2011 to March 2015. They found DAS28-CRP remission rates to be comparable between the two groups with 77% in the IGU and 71% in the SSZ groups, respectively.
A third poster evaluated the efficacy of IGU in 54 RA patients with clinical assessment and ultrasound at 12 and 24 weeks of therapy and reported improvement of both clinical and ultrasound (grey scale and power Doppler signals) evidence of inflammation.
Based on this limited evidence, I wonder if Iguratimod could be a potential therapeutic agent in the rest of the world? It seems that the Japanese are using it in very high-risk patients – the types of patients that are often not appropriate for biologics or other advanced therapeutics.
It seems to have similar efficacy to sulfasalazine, but could have safety advantages. I think more data are needed, particularly long-term safety and in combination with higher doses of methotrexate.
Dr. Jamal is a Clinical Associate Professor at the University of British Columbia and an active staff physician at Vancouver Coastal Health. Her interests include diagnosis and prognosis of early inflammatory arthritis, and timely assessment and access to care for patients with rheumatoid arthritis.View Full Bio