Calcineurin inhibitors for adult-onset Still's disease: a multicentre retrospective cohort study

Objective. To clarify the efficacy and safety of calcineurin inhibitors (CNI) for treating adult-onset Still's disease (AOSD). Methods. This multicentre historical cohort study enrolled the consecutive patients with AOSD according to Yamaguchi classification criteria. The endpoints were set as the time from the initiation of treatment to events, the persistency rate of CNI and safety. Based on the recurrent event data analysis, these endpoints were evaluated for each event. We divided the events into two groups according to the treatment that included CNI or conventional therapy without CNI. Results. One hundred and seventyeight patients with 247 events were analysed. CNI were predominantly used in 72 events with a recurrent history, typical skin rash, high ferritin levels, and/or severe complications such as macrophage activation syndrome, disseminated intravascular coagulation, serositis, meningitis. CNI led to a significantly longer event-free survival (hazard ratio: 0.57, 95% confidential interval: 0.32-0.99) after adjustment of concomitant medications. Subgroup analysis showed that CNI were effective for AOSD patients with high ALT level (hazard ratio: 0.11, 95% confidential interval: 0.02-0.59) and severe complications (hazard ratio: 0.11, 95% confidential interval: 0.01-0.94). The persistency rate of CNI was 71% at 5th year. Adverse events occurred more frequently in the CNI group (18% vs. 8%, p=0.02); however, CNI did not involve in increased risk of adverse events, including nephrotoxicity, after adjustment (p=0.23). Conclusion. Our retrospective analysis suggested that CNI could be an effective and safe option for treating AOSD.