AB0426 COMPARISON OF INFLUENCES OF DIFFERENT CONCOMITANT DRUGS IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH IGURATIMOD, A CONVENTIONAL SYNTHETIC DISEASE-MODIFYING ANTI-RHEUMATIC DRUG DEVELOPED IN JAPAN, IN REAL-WORLD CLINICAL SETTING
Authors: Yuji Hirano, Daisuke Kihira, Yukiyoshi Oishi
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Iguratimod (IGU) is csDMARDs developed in Japan and used in Japanese daily practice since 2012. Although IGU was developed as an anti-inflammatory drug at first, anti-rheumatic effect was found in experiments using type II collagen-induced arthritis model mice <sup>1)</sup>. Main mode of action of IGU was thought to be inhibition of NF-kB resulted in decreased production of IL-6, IL-8 and TNF-alpha <sup>2)</sup>. Clinical trials performed in Japan showed that efficacy of IGU was equal to sulfasalazine when used as monotherapy in patients with RA <sup>3)</sup>. Additive efficacy to MTX was also shown in double-blind randomised trial in RA patients <sup>4)</sup>. We reported efficacy of IGU in daily clinical practice in EULAR2017 <sup>5)</sup>. IGU is prescribed as monotherapy or concomitantly with other DMARDs such as MTX, csDMARDs other than MTX or biological DMARDs. <h3>Objectives</h3> Influences of different concomitant drugs were compared in RA patients treated with IGU in this retrospective study. <h3>Methods</h3> 178 RA patients treated with IGU in our institute from April 2013 to June 2017 were included. Patients were divided into four groups. (1) Group in which IGU was started as monotherapy (MONO-G: n=59). (2) Group in which IGU was added on to MTX treatment without bDMARDs (MTX-G: n=81). (3) Group in which IGU was added on to csDMARDs treatment other than MTX (sulfasalazine, tacrolimus, bucillamin) (CSD-G: n=26). (4) Group in which IGU was added onto bDMARDs treatment. (BIO-G: n=12). Patients' characteristics, time course of disease activity (LOCF analysis), continuation rates of IGU (Kaplan-Meier) and reasons of stopping IGU were investigated and compared between groups. <h3>Results</h3> Baseline characteristics was as below. Mean age was 71.4 years old (yo) in MONO-G, 58.3 yo in MTX-G, 70.1 yo in CSD-G, and 58.7 yo in BIO-G. RA duration was 10.2 years in MONO-G, 8.9 years in MTX-G, 11.2 years in CSD-G, and 15.1 years in BIO-G. SDAI at initiation of IGU was 14.2 in MONO-G, 12.8 in MTX-G, 21.3 in CSD-G, and 18.4 in BIO-G. SDAI was significantly improved over time in all four groups (Fig. 1). There were no significant differences in ΔSDAI from baseline to 1 year between groups by one-way ANOVA (Bonferroni). Continuation rates of IGU at one year and three years were 66.6% and 21.2% in MONO-G, 77.8% and 57.1% in MTX-G, 69.2% and 39.7% in CSD-G and 75.0% and 75.0% in BIO-G. Continuation rate in MTX-G was significantly favorable compared with that in MONO-G and CSD-G by Log-rank test (Fig. 2). Most frequent reason for stopping IGU was liver damage (10 cases). Second frequent reason was intermittent pneumonia in 4 cases and infectious pneumonia in 4 cases. <h3>Conclusion</h3> IGU seemed to be the most tolerant in MTX-G and the second most tolerant in BIO-G. Although higher aged population who might have several comorbidities was included in MONO-G and CSD-G, moderate efficacy of IGU was seen in those groups. Although biological DMARDs is effective in RA patients, the cost is very expensive. IGU is comparative cheap (¥9,200/month) and suitable for RA patients with economic difficulties. As IGU decreased TNF-alpha production via inhibition of NF-kB, MTX+IGU may have similar mode of action with MTX+TNF inhibitor. Although small cases were included in BIO-G, Continuation rate of IGU in BIO-G was good. <h3>References</h3> [1] Aikawa, et al. Inflamm res. 51; 188-194 2002. [2] Kohno, et al. J Rheumatol. 28; 2591-2596 2001. [3] Hara, et al. Mod Rheumatol. 17; 1-9 2007. [4] Ishiguro, et al. Mod Rheumatol. 23; 430-439 2013. [5] Hirano, et al. Ann Rheum Dis. suppl2; 285 2017. <h3>Disclosure of Interests</h3> None declared