• adult onset still’s disease
• inflammation
• treatment

Adult-onset Still’s disease (AOSD) is a rare inflammatory disorder with heterogeneous clinical presentation and unspecific features (spiking fever, pharyngitis, arthritis, skin rash with elevated acute phase reactants).1 Its diagnosis is one of exclusion, and necessitates ruling out many other conditions, notably neoplastic and infectious ones. Based on clinical experience and literature, a ‘dichotomous view’ of AOSD is emerging, with two distinct AOSD clinical subtypes, potentially requiring distinct treatments1 2: a non-Mendelian autoinflammatory disease with pre-eminent systemic symptoms and intense inflammatory state, sometimes associated with life-threatening complications such as reactive haemophagocytic lymphohistiocytosis, and a rheumatic disease with pre-eminent chronic polyarthritis and possibly destructive polyarthritis with lower inflammatory state. Currently, this ‘dichotomous view’ is not only supported by clinical observations, but also by findings on cytokine profiles and responses to biotherapies in some refractory patients.2 Indeed, interleukin (IL)-1β, IL-6 and IL-18 would be associated with ‘systemic AOSD’, whereas tumour necrosis factor alpha (TNF-α), interferon gamma (IFN-γ) and IL-8 would be of greater involvement in ‘rheumatic AOSD’.3–6 Of note, this dichotomous approach remains controversial and the choice of biologics (targeting ‘appropriate’ cytokines) is still empirical in refractory patients. One could hope that cytokine monitoring provides information towards a personalised approach. However, such immunobiological tools are technically difficult to develop for daily practice and remains phantasmagorias even though they would be very useful at the time when several biotherapies are already successfully used or are under evaluation in clinical trials (https://clinicaltrials.gov/).

In Annals of the Rheumatic Diseases, Gabay et al report the results of a multicentre, open-label study evaluating the safety and efficacy of the recombinant IL-18-binding protein (IL-18BP), tadekinig alfa, in patients with difficult-to-treat AOSD.7 IL-18 was indeed reported increased in patients with AOSD and systemic onset juvenile idiopathic arthritis. This work provides the first demonstration of the therapeutic …