Annals of the Rheumatic Diseases

Background: The pro-inflammatory cytokine interleukin (IL)-1 has a central role in the pathogenesis of adult-onset Still’s disease (AOSD), a rare auto-inflammatory condition. Anakinra, has been for years the cornerstone of IL-1-blocking therapy in AOSD. More recently, the monoclonal antibody canakinumab, a new agent blocking IL-1, has become available Objectives: To describe our real-life experience with CNK in a cohort of AOSD patients from a single Italian Center Methods: AOSD patients diagnosed according to Yamaguchi’s criteria followed-up at our Autoinflammatory Unit and treated with CNK for at least 3 months were included. Demographic features, disease characteristics, reasons for CNK introduction, concomitant therapies, variation in systemic steroids dose, adverse events, and response to treatment were retrospectively evaluated. Non-parametric tests were used for statistical comparison Results: 13 patients (5 women; median age 49 years, range 21-74), treated with subcutaneous CNK 4 mg/kg 4-weekly, were identified. Median disease duration before CNK introduction was 12 (6-240) months. After CNK introduction, 2 patients were followed-up for 18 months, 3 for 12 months, 6 for 6 months, 2 for 3 months. CNK was introduced as first-line biologic DMARD in 6 patients. The other 7 patients had been already treated with at least one other bDMARD, for a total of 15 treatment courses (7, anakinra, ANK; 4, tocilizumab; 4, TNF-inhibitors), with a median bDMARD therapy duration of 8 (4-178) months. Previous bDMARDs had been interrupted because of inefficacy (8 cases) or adverse events (AE, 7 cases); of the 7 ANK-treated patients, therapy interruption was due to inefficacy in 3 cases. At CNK introduction, 11 patients were on systemic steroid therapy, prednisone (PDN) equivalent dose 15 (5-80) mg, and 10 were concomitantly receiving a conventional DMARD (7, methotrexate; 2, colchicine; 1, cyclosporine-A). Graphic 1 summarizes main clinical features at CNK introduction. After CNK start, a striking and rapid clinical response was observed, as demonstrated by a substantial decrease of modified Pouchot score and a normalization of acute phase reactants after only 3 months (see Table 1 for details). CNK showed also a significant steroid-sparing effect: median PDN dose was reduced to 7.5 (2.5-12.5) mg at month 3 and 5 (0-7.5) mg at month 6; PDN was stopped in 3 patients (1 at month 3, 1 at month 6, 1 at month 12) due to optimal disease control. CNK was temporarily held-off in 3 patients (zoster reactivation, 1; prostatitis, 1; mild leukopenia, 1). We observed no case of primary inefficacy Table 1. Disease activity and blood tests at canakinumab introduction and during follow-up Daily prednisone dose mg Baseline (n=13 ) 3 months (n=13 ) 6 months (n=11 ) 12 months (n=5 ) 18 months (n=2 ) Pouchot score 15 (5-80) 7.5 (2.5-12.5) 5 (0-7.5) 5 (0-7.5) 2.5 VAS pain 3 (2-5) 1 (0-2) 0 (0-1) 0 0 Erythrocyte sedimentation rate mm/h 7 (2-10) 3 (1-8) 2 (1-4) 1 (1-2) 1 C-reactive protein mg/L 42 (8-120) 21 (2-69) 13 (2-55) 14 (2-41) 11 Ferritin ng/mL 20.8 (3-180) 3.1 (0.5-22.5) 1.6 (0.5-8.4) 1 (0.3-6.3) 0.5 Hemoglobin g/dL 379.5 (161-914) 282 (82-552) 215 (34-464) 177 (77-401) 199 13.1 (9.4-15.7) 13.2 (10.7-15.3) 13.8 (11.5-15.5) 13.9 (11.3-14.3) 13.5 Figure 1. Graphic 1 Main clinical features at canakinumab introduction Conclusion: Our real-life data confirm that CNK is highly effective and safe in AOSD treatment and has significant steroid-sparing effects. CNK showed its efficacy both as first-line therapy and after other bDMARDs failure, also in patients who have previously failed IL-1 inhibition through ANK References: [1] Cavalli G, et al. Treating rheumatological diseases and co-morbidities with interleukin-1 blocking therapies. Rheumatology (2015) [2] Cavalli G, et al. Efficacy of Canakinumab as First-Line Biologic Agent in Adult-Onset Still’s Disease. Arthritis Res Ther (2019) Disclosure of Interests: Alessandro Tomelleri: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, Pfizer, MSD, Nicola Farina: None declared, Elena Baldissera Speakers bureau: Novartis, Pfizer, Roche, Alpha Sigma, Sanofi, Giulio Cavalli Speakers bureau: SOBI, Novartis, Pfizer, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI

FRI0506 EFFICACY AND SAFETY OF CANAKINUMAB IN ADULT-ONSET STILL’S DISEASE: A SINGLE-CENTER REAL-LIFE EXPERIENCE