Development and validation of clinical criteria for the definition of disease activity in adult-onset Still's disease: a cohort study.

The use of heterogeneous empirical definitions to assess disease activity in adult-onset Still's disease limits evidence on the efficacy of immunosuppressive agents. Thus, we aimed to specifically develop and validate definitions of clinical criteria for the assessment of disease activity in adult-onset Still's disease. We used data from the GIRRCS (Gruppo Italiano Di Ricerca in Reumatologia Clinica e Sperimentale) adult-onset Still's disease cohort to develop and validate clinical criteria for disease activity. From Jan 1, 2022, to Dec 31, 2023, consecutive patients attending the Italian rheumatological centres involved in the GIRRCS adult-onset Still's disease were included if they were aged ≥18 years and fulfilled the Yamaguchi criteria for diagnosis of adult-onset Still's disease. Patients' clinical characteristics were assessed at baseline and 3 months and 6 months. Additionally, we used baseline data from the CONSIDER (Canakinumab for treatment of adult-onset Still's disease to achieve reduction of arthritic manifestation) trial to externally validate the criteria (recruitment June 21, 2012, to May 5, 2018). The item reduction was based on correlations between clinical characteristics and disease activity as scored by physicians, principal component analysis, and a longitudinal linear mixed model with disease activity as the dependent variable. Performance of the developed criteria was evaluated using area under the receiver operating characteristic curves (AUROCs), separately for development and validation data. People with lived experience of adult-onset Still's disease were involved in study design and implementation. 187 patients from GIRRCS (130 [70%] in the development cohort and 57 [30%] in the preliminary validation cohort; 94 [50%] female and 93 [50%] male; mean age 40·8 years [SD 17·3]) and 41 patients from the CONSIDER trial (28 [68%] female and 13 [32%] male; mean age 43·0 years [13·1]) were evaluated. Fever, skin rash, arthritis, patient global assessment of at least 2 cm, and C-reactive protein (CRP) greater than 10 mg/L were selected as the criteria for disease activity assessment. Active adult-onset Still's disease was defined as fever and one of the following criteria: skin rash, arthritis, patient global assessment of at least 2 cm, CRP greater than 10 mg/L; or as no fever but at least three of the other criteria (AUROC of 0·93 in development cohort, 0·85 in the preliminary validation cohort, and 0·88 in the external validation cohort). Patients with no fever and no more than one of the aforementioned criteria were considered to have low disease activity (AUROC of 0·86 at 3 months and 0·94 at 6 months in the preliminary validation cohort). Clinically inactive disease was defined as the absence of all five criteria. Disease activity criteria in adult-onset Still's disease were developed to support the attainment of clinically inactive disease as the main treatment target in patient management. None.