SAT0612 The efficacy of calcineurin inhibitors in patients with adult-onset still’s disease: single-centre historical cohort study
Authors: H. Nakamura, Y. Fujieda, M. Kato, K. Oku, T. Bohgaki, O. Amengual, S. Yasuda, T. Atsumi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder generally responsive to corticosteroid therapy, whereas refractory AOSD is often encountered that not controlled by corticosteroid monotherapy. In such cases, methotrexate and biologics including TNF-α, IL-1, or IL-6 inhibitors are used.<sup>1</sup> However, more treatment options are required for refractory AOSD patients who are intolerant to methotrexate or biologics. Calcineurin inhibitors downregulate T cell activation through inhibiting IL-2 transcription and signal transduction. Therefore, calcineurin inhibitors are reasonable therapeutic medication for AOSD since T cells and subsequently activated macrophages play a pathophysiological role in AOSD.<sup>2</sup> Nevertheless, only a few case series have indicated effects of calcineurin inhibitors in clinical practice. <h3>Objectives</h3> To evaluate the efficacy of calcineurin inhibitors in patients with AOSD. <h3>Methods</h3> This is a single-centre historical cohort study comprised of the consecutive patients with AOSD according to Yamaguchi classification criteria, who were attending our Rheumatology Department between January 2000 and December 2016. The primary endpoint was set as the time from the initiation of treatment to event defined as death of any causes, relapse of AOSD requiring an increase of corticosteroid dose, or serious adverse effects. Secondary endpoints were set as the minimum dose of corticosteroid, persistency rate of calcineurin inhibitors, and safety. Based on the recurrent event data analysis, these endpoints were evaluated for each event. We divided the events into two groups according to the treatment that included calcineurin inhibitors (CI+) or conventional therapy without calcineurin inhibitors (CI-), and compared them after adjustment using inverse probability of treatment weighting (IPTW) methods. <h3>Results</h3> Forty-two patients (31 female and 11 male) were enrolled in this study. Mean age was 41 year-old, and median follow-up period 38 months. Thirty-one events in 21 patients were treated with therapeutic regimen including calcineurin inhibitors (CI+, cyclosporine: 7, tacrolimus: 24), and 34 events in 25 patients were treated with the conventional therapy excluding calcineurin inhibitors (CI-). After adjustment, the CI +group had significantly longer event-free survival than the CI- group (figure 1). The weighted hazard ratio (HR) was 0.49 (95% CI, 0.25–0.93, p=0.03). In addition, the CI +group had lower doses of corticosteroid (3.5 vs 6.1 mg/day, p=0.03) when the events occurred. The persistency rate of calcineurin inhibitors was 92% at 5th year. Serious infection occurred in four patients (19%) in the CI +group, and one of them had a fatal course. <h3>Conclusions</h3> Our retrospective analysis suggested that calcineurin inhibitors could be an additional option for AOSD and further prospective studies were desired. <h3>References</h3> [1] Efthimiou P, et al. Diagnosis and management of adult onset Still's disease. Ann Rheum Dis2006. [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 Dis2004. <h3>Disclosure of Interest</h3> None declared