THU0471 Tocilizumab in Refractory Adult-Onset Still’s Disease: Multicenter Study of 27 Patients

Abstract

Background Adult-onset Still’s disease (AOSD) is often refractory to standard immunosuppressive therapy. Tocilizumab (TCZ) has shown efficacy in isolated cases or in small series. Objectives We assess the efficacy of TCZ in AOSD. Methods Multicenter study of 27 patients with AOSD of 18 hospitals diagnosed according to Yamagouchi’s criteria (J Rheumatol 1992;19:424). TCZ was used due to lack of good response to standard therapy or to other biologic agents. Results The 27 patients (20 women/ 7 men), had a mean age of 37.2±15.9 (range 16-71) and an average duration of AOSD of 5.9±4.6 years (range 0.1-17) to onset of TCZ. Prior to the onset of TCZ and besides corticosteroids, patients had recived the following drugs: Metotrexate (26 patients), Anakinra (12), Etanercept (6), Adalimumab (5) and Infliximab (3). TCZ standard dose was 8 mg/k/iv/4 weeks. At TCZ onset, the most frequent clinical manifestations were joint (27 cases), cutaneous (14) and fever (18), along with analytical abnomalities, increase of ESR or CRP (20 cases), anemia (11) or leukocytosis (15). Clinical and analytical improvement was observed soon, 1st month after the onset of TCZ therapy (TABLE). After a mean follow-up of 20.8±12 months, cutaneous manifestations disappeared in 13 of 14 patients (92,9%), fever in 17 of 18 (94.4%) and joint manifestation in 22 of 27 (81,5%). Improvement of analytical abnormalities was observed in most cases with normalization of the blood cell count in 9 of 15 (60%) patients, anemia in 11 of 11 (100%), ESR in 15 of 19 (78.9 % ), CRP in 17 of 20 (85%), hepatic enzymes (AST/ALT) in 3 of 4 (50 %) and ferritin seric levels in 11 of 13 (84,6%). The median [IQR] dose of steroids was reduced from 15 [8.8-25] to 5 [1.3-7.5]. Conclusions In refractory AOSD, TCZ yields early and maintained clinical-analytical response, even in refractory cases to other biological agents. Although TCZ showed global efficacy, joint are more refractory than other systemic manifestations. Disclosure of Interest None Declared

Response to Interleukin-1 Inhibitors in 140 Italian Patients with Adult-Onset Still’s Disease: A Multicentre Retrospective Observational Study

“…Approximately 68% of the patients were found to be responders; half achieved complete remission defined as the total disappearance of signs and symptoms of disease and normalization of laboratory parameters. As reported in previous reports summarized in Table 10 ( Lequerré et al, 2008 ; Laskari et al, 2011 ; Nordström et al, 2012 ; Giampietro et al, 2013 ; Gerfaud-Valentin et al, 2014b ; Cavalli et al, 2015 ; Ortiz-Sanjuán et al, 2015 ; Rossi-Semerano et al, 2015 ), a complete remission was demonstrated in up to 80% of the patients studied.…”

“…Likewise, in a study carried out by Giampietro et al (2013) the most impressive response was obtained in the systemic AOSD pattern; a slightly less dramatic effect was noted in the chronic articular phenotype. Ortiz-Sanjuán et al (2015) likewise reported a persistence of joint involvement after one year of treatment in 41.5% of the patients studied. Definitive conclusions on the real effectiveness of ANA on joint involvement have yet to be drawn.…”

“…Increasing evidence regarding the global efficacy of IL-1 inhibitors (IL-1-INH), such as Anakinra (ANA; IL-1 receptor antagonist) and Canakinumab (CAN; monoclonal anti-IL-1β antibody) has been collected from refractory systemic and articular AOSD patients ( Kontzias and Efthimiou, 2012 ; Ortiz-Sanjuán et al, 2015 ). ANA is a recombinant, non-glycosylated form of human IL-1 receptor antagonist; since it has a very short half-life, daily subcutaneous administrations are necessary.…”

Efficacy of high-dose anakinra in refractory macrophage activation syndrome in adult-onset Still’s disease: when dosage matters in overcoming secondary therapy resistance

“…A successful clinical use of anakinra at the standard dose, in monotherapy or with concomitant DMARDs, has been described in traditional AOSD resistant to conventional therapies and, in some cases, also resistant to at least one biologic agent. 13–15 However, this contrasts with a frequent off-label use of a higher dose anakinra in practice at the dosage up to 200 mg/day (2 mg/kg/day) among adults and 2–4 mg/kg/day among children. 16 In this survey, the frequency of failure was higher among patients treated with anakinra at a dosage of 100 mg/day than those treated with 2 mg/kg/day.…”

The reduction of concomitant glucocorticoids dosage following treatment with IL-1 receptor antagonist in adult onset Still’s disease. A systematic review and meta-analysis of observational studies

“…Five manuscripts were excluded after assessment of the full text due to the lack of information concerning the concomitant GCs therapy and despite data about the clinical efficacy of anakinra. 19–23 Amongst the selected manuscripts, one open randomized multicenter trial with two parallel groups 24 and eight observational single-arm retrospective studies 25–32 were retrieved. Concerning the randomized trial, 24 22 patients were randomized to anakinra or synthetic disease modifying anti-rheumatic drugs (DMARDs), but we considered only the 12 patients randomized to anakinra according to the general design of this work.…”