Macrophage activation syndrome in patients with adult-onset Still’s disease under tocilizumab treatment. A single-center observational study

OBJECTIVES Macrophage activation syndrome (MAS) developed under tocilizumab treatment poses a diagnostic challenge. This study aims to demonstrate the frequency and the clinical features of MAS developed in patients with adult-onset Still's disease (AOSD) receiving tocilizumab. METHODS The consecutive AOSD patients treated with tocilizumab in our institution from April 2008 to March 2020 were studied. The frequency of clinically diagnosed MAS during tocilizumab treatment, their conformity to the several criteria relevant for MAS, and laboratory characteristics compared to AOSD flare were investigated. RESULTS Of the 20 AOSD patients treated with tocilizumab, six developed clinically diagnosed MAS, four immediately after starting tocilizumab and two after long-term treatment. Some of them had already met the MAS criteria before starting tocilizumab. At MAS diagnosis, although some did not meet the MAS criteria due to lack of fever and/or the lower ferritin levels, all consistently showed sharp increases in ferritin along with marked abnormal changes in two or more different markers of organ damage, unlike the AOSD flares. CONCLUSION MAS is not a rare complication in AOSD patients receiving tocilizumab. The clinical similarities between systemic AOSD and MAS, and substantial alterations in MAS features by inhibition of interleukin-6 signaling may limit the utility of the existing diagnostic/classification criteria in diagnosing MAS under tocilizumab treatment. The emergence of abnormalities in MAS-related organ damage markers with a rapid elevation of ferritin should be considered as MAS development in AOSD patients receiving tocilizumab even if the patients are afebrile or have relatively low ferritin levels.