FRI0585 EFFICACY OF CANAKINUMAB AS FIRST-LINE BIOLOGIC AGENT IN ADULT-ONSET STILL’S DISEASE
Authors: Giulio Cavalli, Alessandro Tomelleri, Giacomo De Luca, Corrado Campochiaro, Elena Baldissera, Lorenzo Dagna
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Adult-onset Still's disease (AOSD) is a rare auto-inflammatory condition characterized by fever, arthritis, skin rash, and multi-organ inflammation. The pathogenesis of AOSD is centrally mediated by the pro-inflammatory cytokine interleukin (IL)-1β; anakinra, a recombinant inhibitor of the IL-1β receptor, has thereby become the cornerstone of biologic therapy for AOSD. More recently, a new agent blocking IL-1β has become available, that is, the monoclonal antibody canakinumab. <h3>Objectives</h3> So far, canakinumab has been used in the treatment of AOSD following failure of multiple lines of biologic therapy, including anakinra. Here, we describe the use of canakinumab as first-line biologic agent in 6 patients with AOSD, and report the highly promising results of this treatment approach. <h3>Methods</h3> Six patients with severe, DMARD-refractory AOSD received canakinumab at the approved dose of 4 mg/kg once every 4 weeks following failure of conventional treatment with corticosteroids and methotrexate. Patient characteristics and response to therapy were recorded. <h3>Results</h3> In all patients, treatment with canakinumab led to striking and rapid clinical responses, within days of initiation. Fever and skin rash disappeared first and did not recur, followed by progressive and sustained improvement in arthritis. Inflammatory organ involvement also responded to treatment: for example, we observed resolution of pericardial inflammation in two patients, as revealed by cardiac ultrasound; another patient had hepatosplenomegaly, which also reverted to normal upon treatment. A striking reduction in serum pro-inflammatory markers C-reactive protein, erythrocyte sedimentation rate, and ferritin mirrored the efficacy on clinical manifestations. These effects amounted to a significant decrease in the modified Pouchot score for measuring disease severity (average score before canakinumab treatment: 6; after: 1.25; statistical significance of difference evaluated with Mann-Whitney: p=0.02), and allowed for tapering or discontinuation of concomitant therapy: specifically, corticosteroid treatment was completely discontinued in two patients and substantially reduced in two patients, whereas methotrexate was stopped in one patient. <h3>Conclusion</h3> In this study, first-line biologic therapy of AOSD with canakinumab resulted in rapid and marked efficacy, ultimately leading to full clinical remissions in all patients, and allowing for robust steroid-sparing effects. So far, canakinumab in AOSD has mostly been used as a last line of treatment following failure of multiple other agents, including anakinra. Early treatment, as described in this study, is nevertheless advisable and may reduce chances of chronic disease and permanent damage. <h3>References</h3> [1] Cavalli G, Dinarello CA: Treating rheumatological diseases and co-morbidities with interleukin-1 blocking therapies. Rheumatology (Oxford)2015, 54(12):2134-2144. [2] Cavalli G, Franchini S, Aiello P, Guglielmi B, Berti A, Campochiaro C, Sabbadini MG, Baldissera E, Dagna L: Efficacy and safety of biological agents in adult-onset Still's disease. Scand J Rheumatol2015, 44(4):309-314. <h3>Disclosure of Interests</h3> Giulio Cavalli: None declared, Alessandro Tomelleri: None declared, Giacomo De Luca Speakers bureau: Pfeizer, Sobi, Corrado Campochiaro Consultant for: Dr Corrado Campochiaro received consultation honoraria from Pfizer., Elena Baldissera Consultant for: Consultation honoraria from Novartis and Rottapharm, Speakers bureau: Pfeizer, Sobi, Novartis, Lorenzo Dagna: None declared