Background Adult onset Still's disease (AOSD) is a rare inflammatory disorder of unknown etiology. Non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoid and disease modifying anti-rheumatic drugs (DMARDs) are prescribed as therapeutic agents for AOSD. The pathogenesis of AOSD remains partially unknown, but the pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-6 and IL-18 have a major role in its pathogenesis. Therefore, these cytokines have been considered of promising therapeutic target in AOSD patients. Recently, there are some reports on the treatment with various biologic agents in refractory AOSD patients with conventional therapy.
Objectives In this study, we described and compared the clinical responsiveness of biologic agents in refractory Korean AOSD patients.
Methods We retrospectively collected medical records of AOSD patients who were refractory to conventional therapy and treated with biologic agents such as TNF-α inhibitors, anakinra, tocilizumab and abatacept from 2003 to 2013 in Hanyang University Hospital.
Results There were 37 patients composed of 24.3% of male and 75.7% of female. The mean age was 39.8±12.7 and the mean age of disease onset was 32.1±13.5 years. The disease duration was 78.7±49.9 months and the prescribed time of biologics was 34.9±37.3 months from initial diagnosis. Among them, 13 patients prescribed more than two biologic agents. TNF-α inhibitors (etanercept n=8, adalimumab n=5, infliximab n=16, infliximab biosimilar n=6, 69.8%), tocilizumab (n=13, 24.5%), anakinra (n=2, 3.8%) and abatacept (n=1, 1.9%) were prescribed in order. Their doses and administration were similar to the conventional therapy of rheumatoid arthritis. The response rate of tocilizumab (84.6%) was higher than TNF-α inhibitors (45.9%) and anakinra (50.0%) (P<0.05). There was no statistical difference of laboratory findings and clinical disease activity at initial point of biologic agents. There were 7 cases who switched from one TNF-α inhibitor to another TNF-α inhibitor due to lack of efficacy, but only 2 cases showed response to switched TNF-α inhibitor. And there were also 6 cases who changed from TNF-α inhibitor to tocilizumab, only 1 case was unresponsive to tocilizumab. The mean duration of prescribed biologic agents was 7.0±10.8 months. The causes of discontinuation were less effectiveness (40.5%), adverse events (24.3%), remission (13.5%) and other causes such as economics, patient's desire and so on (13.5%). Biologic agents were discontinued in 3 cases because of both lack of effectiveness and adverse events. The adverse events were developed in all of patients with anakinra and abatacept, 46.2% of patients with tocilizumab and 27% of patients with TNF-α inhibitors.
Conclusions Tocilizumab showed the most responsiveness among biologic agents in Korean AOSD patients refractory to conventional therapy. This finding suggested that tocilizumab could be considered as the first therapeutic option in refractory patients with conventional treatment when anakinra is not available.
Disclosure of Interest : None declared