Adult-onset Still’s disease (AOSD) is a rare systemic autoinflammatory disorder that can lead to symptoms like fever, arthritis, and hyperferritinaemia. It is seen as an adult form of systemic juvenile idiopathic arthritis (SJIA). Treatment options such as glucocorticoids and biologic DMARDs are available, but there are no standardized criteria for assessing disease activity. Current studies have used inconsistent definitions of response, which have affected the quality and comparability of research. After this, the European Alliance of Associations for Rheumatology (EULAR) launched an initiative to develop consensus-based Points to Consider (PtCs) to help create a validated set of criteria for AOSD activity assessment.
This study aimed to evaluate the EULAR Points to Consider for assessing disease activity in AOSD. These PtCs were intended to guide the development of specific, validated criteria for disease activity and to enable consistent clinical evaluation, improved research methodology, and harmonisation with the concept of Still’s disease as a continuum across pediatric and adult populations.
After approval by the EULAR Executive Committee, a multinational Task Force was formed comprising rheumatologists, paediatric rheumatologists, health professionals, methodologists, fellows, and patient representatives from 7 European countries. The work followed revised EULAR standardised operating procedures. The Task Force conducted 2 main components: (1) a systematic literature review (SLR) and (2) a structured, three-round Delphi consensus process.
The SLR identified clinical, laboratory, radiological, and patient-reported variables linked to AOSD disease activity. In the first round of the Delphi exercise, experts suggested additional features for potential inclusion. A refined list of 28 variables and 5 patient-reported outcomes (PROs) was rated in Delphi rounds 2 and 3. Consensus was defined as ≥75% agreement on variables judged required or important. The results informed the development of draft PtCs. Each PtC underwent iterative discussion and voting; ≥75% approval in the first voting round was required for acceptance. Levels of evidence were assigned according to Oxford Centre for Evidence-Based Medicine standards, and all Task Force members rated their level of agreement with each final statement.
A total of 11 EULAR Points to Consider were formulated, supported by evidence from the SLR and the consensus process. Fever was identified as the single most frequent and reliable clinical marker of disease activity, with experts agreeing on a threshold of ≥38.5°C. Although the characteristic spiking pattern of fever is common, it was not deemed essential. A fever duration of 3 to 7 days was suggested for defining flares, though further study is required. Skin rash, particularly evanescent, salmon-pink eruptions occurring with fever, was accepted as a meaningful indicator of activity.
Joint involvement, including arthralgia and arthritis, was recognised as common at onset and during flares. Swollen joints were considered more reliable than tender joints due to the multifactorial nature of pain. Systemic symptoms like splenomegaly, lymphadenopathy, and serositis (pleuritis and pericarditis) were strongly linked to disease activity. Their assessment is limited in routine practice due to imaging requirements and the need to exclude infection or malignancy.
Laboratory markers got strong support. Hyperferritinaemia was detected as a laboratory marker consistently linked to disease activity and reflecting both relapse and onset. CRP and ESR are widely recognized as helpful, readily available markers, though their interpretation is confounded in MAS and in patients treated with IL-6 inhibitors. Increased liver enzymes and neutrophilic leukocytosis were accepted as valid indicators. The only PRO that obtained consensus was the patient global assessment (VAS), which was recognised as useful but needed further validation.
Researchers have highlighted the need for a precise definition of remission in AOSD, which currently lacks standardization. The Task Force advocates that remission be defined as the sustained absence of disease activity, an important target in a treat-to-target approach. They underlined the need for disease-specific patient-reported outcomes, given the lack of qualitative research on the patient perspective.
The EULAR Task Force developed 11 consensus-based Points to Consider guiding the development of validated criteria for assessing disease activity in AOSD. These points highlight the integration of clinical symptoms, laboratory findings, and patient-reported results and acknowledge limitations in current evidence and feasibility. Future studies are required to refine these criteria through collaboration across rheumatology disciplines and to recognize Still’s disease as a single condition.
References: Ruscitti P, et al. The EULAR points to consider regarding the development of criteria for the assessment of the disease activity in adult-onset Still’s disease. EULAR Rheumatology Open. 2025;0(0). doi:10.1016/j.ero.2025.11.015
