Abstract
BackgroundAdult-onset Still’s disease (AOSD) is a rare inflammatory condition characterized by fever, rash, and arthritis. Because of its rarity, clinical trials are inherently small and often uncontrolled. Our objective was to develop recommendations for the use of interleukin (IL)-1 inhibitors in the management of patients with AOSD, based on the best evidence and expert opinion.MethodsA panel of 10 experts (9 rheumatologists and 1 pediatrician) was established. The first step was dedicated to a comprehensive literature review and development of statements. Two separate literature searches were performed on the MEDLINE (Pubmed), EMBASE, and BIOSIS databases through April 2018 to identify (1) differences and similarities between AOSD and pediatric Still’s disease (systemic juvenile idiopathic arthritis [SJIA]) and (2) the efficacy and safety of IL-1 inhibitors in AOSD treatment. 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, > 66% of voters selected scores 3 to 5; negative, > 66% of voters selected scores 1 or 2. In the third step, the voting results were analyzed, and the statements were finalized.ResultsEleven statements were developed. Forty-six of 67 rheumatologists (72%) participated in the Delphi process. A positive consensus was reached after the first round of voting and was full (> 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 the first and as a 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 response to another one. The lack of studies comparing early versus late treatment did not allow to draw conclusions; however, data from SJIA suggest a better response in early treatment.ConclusionsThe Delphi method was used to develop recommendations that we hope will help clinicians in the management of patients with AOSD refractory to conventional therapies.
Highlights
Still’s disease is a rare systemic inflammatory disorder that can develop both in adults and children and is characterized by a wide spectrum of manifestations, including a typical triad of symptoms: daily spiking fever, polyarthritis, and a characteristic salmon-colored skin rash [1]
A comprehensive search of the literature was planned to gather the available evidence on the relationship between Systemic Juvenile Idiopathic Arthritis (SJIA) and Adult Onset Still’s Disease (AOSD) and on IL-1β blockade in AOSD
A total of 60 case reports, mostly related to the use of anakinra were identified; 7 case reports described the use of canakinumab in AOSD [79,80,81,82,83,84,85], and 3 case reports documented the use of rilonacept in AOSD [83, 86, 87]; the complete list of case reports can be viewed in Additional file 1: Table S3 [27, 59, 79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134]
Summary
Still’s disease is a rare systemic inflammatory disorder that can develop both in adults and children and is characterized by a wide spectrum of manifestations, including a typical triad of symptoms: daily spiking fever, polyarthritis, and a characteristic salmon-colored skin rash [1]. The childhood form of the disease is currently termed systemic juvenile idiopathic arthritis (SJIA), while the adult form is known as adult-onset Still’s disease (AOSD) [1]. Based on the presence of predominant “systemic” or “chronic articular” manifestations, two different subtypes of AOSD have been proposed [6]. These two subtypes are characterized by distinct serological profiles, with evidence of a major pro-inflammatory state in the systemic form compared to the articular form [6,7,8,9,10]. Adult-onset Still’s disease (AOSD) is a rare inflammatory condition characterized by fever, rash, and arthritis. Our objective was to develop recommendations for the use of interleukin (IL)-1 inhibitors in the management of patients with AOSD, based on the best evidence and expert opinion
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