OP0166 THE EFFICACY OF CALCINEURIN INHIBITORS IN PATIENTSWITH ADULT-ONSET STILL’S DISEASE: MULTI-CENTRE HISTORICAL COHORT STUDY
Authors: Masato Tarumi, Hiroyuki Nakamura, Yuichiro Fujieda, Hirohiko Kitagawa, Ryo Hisada, Yuka Shimizu, Ikuma Nakagawa, Akito Tsutsumi, Takashi Kurita, Hiroshi Kataoka, Masaya Mukai, Hideki Kasahara, Atsushi Noguchi, Yoshiharu Amasaki, Tetsuya Horita, Tatsuya Atsumi
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder generally responsive to corticosteroid (CS) therapy, whereas cases not responding CS monotherapy are frequently found in clinical practice. In such cases, methotrexate and/or biologics including TNF-α, IL-1, or IL-6 inhibitors are used [1]. However, further treatment options are required for refractory AOSD patients who are intolerant to methotrexate and/or biologics. Calcineurin inhibitors (CNI) downregulate T cell activation through inhibiting IL-2 transcription and signal transduction. Therefore, they are reasonable therapeutic medication for AOSD considering T cells and subsequently activated macrophages play a pathophysiological role in AOSD [2]. Nevertheless, only a few case series have indicated effects of CNI for difficult AOSD. <h3>Objectives</h3> To evaluate the efficacy of CNI in patients with AOSD. <h3>Methods</h3> This is a multi-centre historical cohort study comprised the consecutive patients with AOSD in accordance with Yamaguchi classification criteria. The primary endpoint was set as the time from the initiation of treatment to event defined as death of any causes or relapse of AOSD requiring an increase of CS dose. Secondary endpoints were set as persistency rate of CNI and safety. Based on the recurrent event data analysis, these endpoints were evaluated for each event. We compared the frequency of events between two groups according to the treatment that included calcineurin inhibitors (CNI+) or conventional therapy without calcineurin inhibitors (CNI-). <h3>Results</h3> One hundred seventy-eight patients were enrolled in this study. Mean age was 46 year-old, and median follow-up period 36 months. Seventy-one events in 56 patients were treated with therapeutic regimen including CNI (CNI+, cyclosporine: 14, tacrolimus: 60), and 176 events in 138 patients were treated with the conventional therapy excluding CNI (CNI-). CNI were used in AOSD patients with recurrent history, high ferritin level, serositis, hemophagocytic syndrome (HPS) and/or disseminated intravascular coagulation (DIC). The CNI+ group had longer event-free survival than the CNI- group (83% versus 75% at 5th year). The hazard ratio (HR) was 0.57 (95% CI, 0.32-0.99) after adjustment of initial dose of CS and other concomitant medications. Subgroup analysis showed that CNI were more effective for AOSD patients with high ALT levels (≥ 80 IU/L) and/or severe complications such as HPS and DIC. The persistency rate of CNI was 71% at 5th year. Adverse events occurred more frequently in the CNI+ group than in the CNI- group (18% versus 8%, p = 0.04); however, serious adverse events did not increase in the CNI+ group (3% versus 2%). AOSD-related mortality had never been found in the observation period. One patient had a fatal course due to septic shock in the CNI+ group. <h3>Conclusion</h3> Our retrospective analysis suggested that CNI could be an additional option for treating AOSD with acceptable safety. <h3>References</h3> [1] Efthimiou P, et al. Diagnosis and management of adult onset Still's disease. Ann Rheum Dis. 2006. [2] Chen DY, et al. Predominance of Th1 cytokine in peripheral blood and pathological tissues of patients with active untreated adult onset Still's disease Ann Rheum Dis. 2004. <h3>Disclosure of Interests</h3> Masato Tarumi: None declared, Hiroyuki Nakamura: None declared, Yuichiro Fujieda: None declared, Hirohiko Kitagawa: None declared, Ryo Hisada: None declared, Yuka Shimizu: None declared, Ikuma Nakagawa: None declared, Akito Tsutsumi: None declared, Takashi Kurita: None declared, Hiroshi Kataoka: None declared, Masaya Mukai: None declared, Hideki Kasahara: None declared, Atsushi Noguchi: None declared, Yoshiharu Amasaki: None declared, Tetsuya Horita: None declared, Tatsuya Atsumi Grant/research support from: Astellas Pharma Inc., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co. Ltd., Otsuka Pharmaceutical Co., Ltd. and Pfizer Inc., Alexion Inc., Bayer Yakuhin, Ltd,Otsuka Pharmaceutical Co., Ltd. Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Eisai Co., Ltd., Bristol-Myers Squibb Co., Daiichi Sankyo Co. Ltd., Mitsubishi Tanabe Pharma Co., Asahi Kasei Pharma Co., Consultant for: ONO PHARMACEUTICAL CO., LTD Sanofi K.K. Daiichi Sankyo Co., Ltd. Pfizer Inc., Speakers bureau: Mitsubishi Tanabe Pharma Co., Chugai Pharmaceutical Co., Ltd., Astellas Pharma Inc., Takeda Pharmaceutical Co., Ltd., Pfizer Inc.,Daiichi Sankyo Co. Ltd., Bristol-Myers Squibb Co., Eli Lilly Japan K.K.