THU0569 MANAGEMENT OF ADULT-ONSET STILL’S DISEASE (AOSD) WITH IL-1 INHIBITORS: EVIDENCE- AND CONSENSUS-BASED STATEMENTS BY A PANEL OF ITALIAN EXPERTS
Authors: Serena Colafrancesco, Maria Manara, Alessandra Bortoluzzi, Teodora Serban, Gerolamo Bianchi, Luca Cantarini, Francesco Ciccia, Lorenzo Dagna, Marcello Govoni, Carlomaurizio Montecucco, Roberta Priori, Angelo Ravelli, Paolo Sfriso, Luigi Sinigaglia
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Still's disease is a rare autoinflammatory disease, presenting in both pediatric [systemic juvenile idiopathic arthritis (SJIA)] and adult patients [adult-onset Still's disease (AOSD]. Due to the rarity of the disease, clinical trials are limited and treatment guidelines are not available. In patients refractory to the classical therapy with NSAIDs, corticosteroids and DMARDs, the introduction of drugs targeting IL-1 has greatly expanded treatment options. Among these, canakinumab, a human monoclonal anti-IL-1β antibody, and anakinra, a human recombinant IL-1RA, have been recently approved for the treatment of refractory patients. <h3>Objectives:</h3> To produce recommendations, based on evidence and expert consensus, that can help clinicians in choosing the most appropriate treatment of AOSD, with particular attention to anti-IL-1 therapies, in order to achieve disease remission before the development of complications. <h3>Methods:</h3> The recommendations development process took place from April to October 2018 and consisted of three steps. The first step was dedicated to a comprehensive literature review and development of statements. Two separate literature searches were performed: a) similarities and differences between SJIA and AOSD; b) efficacy and safety of IL-1 blockade in AOSD. The issue related to the treatment of AOSD with anti-IL1 therapies was specified into 4 questions: 1) efficacy and safety; 2) comparison among IL-1 inhibitors; 3) early versus late treatment; 4) systemic versus chronic articular pattern of the disease. In the second step, the statements were submitted in a Delphi process to a panel of 67 rheumatologists. Consensus threshold was set at 66%: positive, &gt; 66% of voters selected scores 3 to 5; negative, &gt; 66% of voters selected scores 1 or 2. At the third step of the consensus process, the voting results were analyzed, and the statements were finalized. <h3>Results:</h3> In the two literature searches, 332 and 358 publications were identified; 30 and 25 publications, respectively, were selected according to the inclusion criteria. Based on the review of the literature and personal clinical experience, 11 statements were developed. 48/67 rheumatologists (72%) participated to the Delphi process. Positive consensus was reached after the first round of voting and was full (&gt; 95%) on the majority of statements. A large consensus was achieved in considering AOSD and SJIA as the same disease. The use of anti-IL-1 therapies in refractory patients was considered quite safe and effective both as first and as subsequent line of biologic treatment, especially in systemic patients. Because of the lack of head-to-head comparisons, a different profile of efficacy among IL-1 inhibitors could not be established. There was a large consensus that failure of the first IL-1 inhibitor does not preclude a therapeutic response with another one. The lack of studies comparing early versus late treatment in AOSD patients did not allow to draw conclusions, however data from SJIA suggest a better response in early treated patients. <h3>Conclusion:</h3> The Delphi method was used to develop recommendations that we hope will help clinicians in the management of patients with AOSD refractory to conventional therapies. <h3>Acknowledgement:</h3> Editorial support was provided by Springer Healthcare Communications and funded by Novartis Farma, Italy. <h3>Disclosure of Interests:</h3> Serena Colafrancesco: None declared, Maria Manara: None declared, Alessandra Bortoluzzi: None declared, Teodora Serban: None declared, Gerolamo Bianchi: None declared, Luca Cantarini: None declared, Francesco Ciccia Grant/research support from: CELGENE, PFIZER, Consultant for: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, Paid instructor for: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, JANSSEN, Speakers bureau: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, JANSSEN, MSD, ROCHE, AMGEN, Lorenzo Dagna Consultant for: Prof Lorenzo Dagna received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Sanofi-Genzyme, and SOBI., Marcello Govoni: None declared, Carlomaurizio Montecucco: None declared, Roberta Priori: None declared, Angelo Ravelli Grant/research support from: Angelini, AbbVie, Bristol-Myers Squibb, Johnson &amp; Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Consultant for: Angelini, AbbVie, Bristol-Myers Squibb, Johnson &amp; Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Speakers bureau: Angelini, AbbVie, Bristol-Myers Squibb, Johnson &amp; Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Paolo Sfriso: None declared, Luigi Sinigaglia Speakers bureau: Yes, I,ve been invited speaker by Amgen, Ely Lilly, UCB, Abbvie, Roche and BMS.