OP0164 LONG-TERM SAFETY OF ANAKINRA IN PATIENTS WITH SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS FROM THE PHARMACHILD REGISTRY
Authors: G. Giancane, R. Papa, S. Vastert, F. Bagnasco, J. F. Swart, P. Quartier, M. Hofer, J. Anton, S. Kamphuis, H. Sanner, M. Glerup, F. De Benedetti, E. Tsitsami, A. Remesal, E. Moreno Ruzafa, J. De Inocencio, C. Myrup, C. Pallotti, I. Koné-Paut, K. Franck-Larsson, H. Malmstrom, S. Cederholm, A. Pistorio, N. Wulffraat, N. Ruperto
Journal: Annals of the Rheumatic Diseases (2021)

Background: Systemic juvenile idiopathic arthritis (SJIA) is characterized by extra-articular manifestations, as fever and rash, and rarely associated by a potentially lethal complication as macrophage activation syndrome (MAS). Anakinra is a recombinant human interleukin (IL)-1 receptor antagonist whose efficacy and safety profile has been studied for patients with SJIA. Objectives: To evaluate the long-term safety profile of anakinra in patients with SJIA. Methods: Data from patients with SJIA enrolled in the Pharmachild registry before 30 September 2018 and treated with anakinra were analyzed. The study endpoints were the occurrence of non-serious adverse events (AEs) of at least moderate severity and serious AEs (SAEs), including macrophage activation syndrome (MAS), and the duration of anakinra treatment with reasons for discontinuation. All endpoints were analyzed overall, by 6 month-time windows and in different treatment sets represented by those patients continuously treated with anakinra for at least 12, 18 and 24 months (set-12, -18, -24, respectively). Results: 306 patients were enrolled. 46%, 34% and 28% of them had been treated for at least 12, 18 and 24 months, respectively. 201 AEs, mostly represented by infections, were reported for 509.3 patient-years (py) with an overall incidence rate (IR) of 39.5/100 py. Among 56 SAEs (IR 11.0/100 py), (Table 1) 23.2% were infections and 19.6% MAS episodes. The IR of AEs was higher during the first 6 months of anakinra, followed by decreasing IR in the different long-term treatment sets. Treatment discontinuation occurred in 76% of patients, most in the first 6 months, due to inefficacy (43%), remission (31%) or AEs/intolerance (15%). No deaths or malignancies occurred during anakinra treatment. Table 1. Number of SAEs and incidence rates (95% CI) by overall PT decreasing order and time window in the complete set (events with a frequency &gt;1 by overall SOC and &gt;1 by overall PT were reported) Only time windows &lt;13 months were reported in the present table. Time window 1-6 months 7-12 months Overall N 306 194 306 Patient-time (years) 117.3 80.2 509.3 SOC PT n Rate (95% CI) n Rate (95% CI) n Rate(95% CI) All All 33 28.1 (19.1-41.5) 4 5.0 (1.9-13.2) 56 11.0 (7.9-15.2) Infections and infestations All 7 6.0 (2.9- 12.4) 1 1.2 (0.2- 8.8) 13 2.6 (1.4- 4.8) Pneumonia 2 1.7 (0.4- 6.8) 1 1.2 (0.2- 8.8) 4 0.8 (0.3- 2.1) Immune system disorders All 7 6.0 (2.8- 12.5) 1 1.2 (0.2- 8.8) 11 2.2 (1.1- 4.1) Haemophagocytic lymphohistiocytosis 7 6.0 (2.8- 12.5) 1 1.2 (0.2- 8.8) 11 2.2 (1.1- 4.1) Injury, poisoning and procedural complications All 5 4.3 (1.8- 10.2) - - 9 1.8 (0.9- 3.4) Infusion related reaction 1 0.9 (0.1- 6.0) - - 2 0.4 (0.1- 1.6) Injection related reaction 4 3.4 (1.3- 9.1) - - 6 1.2 (0.5- 2.6) Metabolism and nutrition disorders All 3 2.6 (0.8- 7.9) - - 4 0.8 (0.3- 2.1) Skin and subcutaneous tissue disorders All 3 2.6 (0.8- 7.9) 1 1.2 (0.2- 8.8) 4 0.8 (0.3- 2.1) Blood and lymphatic system disorders All 1 0.9 (0.1- 6.1) - - 2 0.4 (0.1- 1.6) General disorders and administration site conditions All 1 0.9 (0.1- 6.1) 1 1.2 (0.2- 8.8) 2 0.4 (0.1- 1.6) Investigations All 2 1.7 (0.4- 6.8) - - 2 0.4 (0.1- 1.6) Nervous system disorders All 1 0.9 (0.1- 6.0) - - 2 0.4 (0.1- 1.6) Surgical and medical procedures All 1 0.9 (0.1- 6.0) - - 2 0.4 (0.1- 1.5) Abbreviations: SAE, serious adverse event; SOC, system organ class; PT, preferred term, MedDRA version 21.1; N, number of patients ever treated with anakinra during the time window irrespectively of the length of any unexposed periods; 95% CI, 95% Confidence Interval. Conclusion: The results of the present study confirm the long-term safety profile of anakinra in SJIA patients and show a decreasing overall incidence rate of AEs over time. Disclosure of Interests: Gabriella Giancane Grant/research support from: The study was funded by SOBI Swedish, Riccardo Papa Grant/research support from: The study was funded by SOBI Swedish, Sebastian Vastert Grant/research support from: The study was funded by SOBI Swedish, Francesca Bagnasco Grant/research support from: The study was funded by SOBI Swedish, Joost F. Swart Grant/research support from: The study was funded by SOBI Swedish, Pierre Quartier Grant/research support from: The study was funded by SOBI Swedish, michael hofer Grant/research support from: The study was funded by SOBI Swedish, Jordi Anton Grant/research support from: The study was funded by SOBI Swedish, Sylvia Kamphuis Grant/research support from: The study was funded by SOBI Swedish, Helga Sanner Grant/research support from: The study was funded by SOBI Swedish, Mia Glerup Grant/research support from: The study was funded by SOBI Swedish, Fabrizio De Benedetti Grant/research support from: The study was funded by SOBI Swedish, Elena Tsitsami Grant/research support from: The study was funded by SOBI Swedish, Agustin Remesal Grant/research support from: The study was funded by SOBI Swedish, Estefania Moreno Ruzafa Grant/research support from: The study was funded by SOBI Swedish, Jaime de Inocencio Grant/research support from: The study was funded by SOBI Swedish, Charlotte Myrup Grant/research support from: The study was funded by SOBI Swedish, Chiara Pallotti Grant/research support from: The study was funded by SOBI Swedish, Isabelle Koné-Paut Grant/research support from: The study was funded by SOBI Swedish, Karin Franck-Larsson Employee of: I am employee of SOBI pharmaceutical company, Hakan Malmstrom Employee of: I am employee of SOBI pharmaceutical company, Susanna Cederholm Employee of: I am employee of SOBI pharmaceutical company, Angela Pistorio Grant/research support from: The study was funded by SOBI Swedish, Nico Wulffraat Grant/research support from: The study was funded by SOBI Swedish, Nicolino Ruperto Speakers bureau: NR has received honoraria for consultancies or speaker bureaus (&lt; 10.000 USD each) from the following pharmaceutical companies in the past 3 years: Ablynx, Astrazeneca-Medimmune, Bayer, Biogen, Boehringer, Bristol Myers and Squibb, Celgene, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Hoffmann-La Roche,Janssen, Merck, Novartis, Pfizer, R-Pharma, Sinergie, Sobi and UCB., Consultant of: NR has received honoraria for consultancies or speaker bureaus (&lt; 10.000 USD each) from the following pharmaceutical companies in the past 3 years: Ablynx, Astrazeneca-Medimmune, Bayer, Biogen, Boehringer, Bristol Myers and Squibb, Celgene, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Hoffmann-La Roche,Janssen, Merck, Novartis, Pfizer, R-Pharma, Sinergie, Sobi and UCB., Grant/research support from: The IRCCS Istituto Giannina Gaslini (IGG), where NR works as full-time public employee has received contributions (&gt; 10.000 USD each) from the following industries in the last 3 years: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties.