Background Patients with adult-onset Still's disease (AOSD) experience frequent relapses. Several case series and cohort studies showed the relatively short-term effectiveness of tocilizumab (TCZ), an anti-interleukin-6 receptor monoclonal antibody, on the disease activity of AOSD. However, frequency of AOSD relapses have not ever been investigated thoroughly, and long-term effectiveness of TCZ on preventing relapses is uncertain.
Objectives We aimed to investigate frequency of AOSD relapses and to examine the effectiveness of TCZ on preventing relapses of AOSD.
Methods Clinical data of all the patients with AOSD (n=40) under regular follow up at our institute in June 2013, including 10 patients who used TCZ, were analyzed retrospectively. We confirmed the diagnosis of AOSD by chart review, according to the criteria proposed by Yamaguchi et al. . A relapse was defined as worsening in disease activity requiring the increase in the dose of glucocorticoids at least by 50% or requiring restart of glucocorticoids when the treatments were glucocorticoids-free. Relapse free rate was analyzed by Kaplan-Meier method.
Results Twenty-nine (72.5%) patients were female. Median (interquartile range, IQR) age of disease onset was 39 (29-52) years old. Median (IQR) duration of disease in June 2013 was 86 (41-193) month. Treatments at the time of observation were as follows; glucocorticoid alone, 9; methotrexate alone, 3; glucocorticoid and methotrexate, 8; glucocorticoid and other immunosuppressant, 1; with TCZ, 8; with etanercept, 2; and treatment-free, 9. A total of 87 relapses were documented. Thirteen (32.5%) patients had not experienced any relapse. The number of relapses significantly increased as disease duration became longer (Spearman's ρ=0.63, p<0.01). Of the 27 patients with relapses, 21 (78%) patients relapsed within 3 years after the commencement of treatment for AOSD. Relapse rate per patient-year stratified by the 5-year period decreased gradually from 0.29 to 0.09 times per patient-year. Ten patients with refractory or relapsing disease received 8 mg/kg TCZ every 2 to 4 week. Median (IQR) duration from disease onset to commencement of TCZ and from commencement of TCZ to data collection was 16 (6-77) months and 31 (9-47) months, respectively. Eleven relapses were observed before using TCZ, and no relapse was observed during TCZ. Relapse free rate of the 10 patients after using TCZ was significantly better in the comparison with all the 40 patients at baseline (100% and 79% at 6 month, p=0.03; Figure). Four patients had discontinued TCZ because of sustained remission. Two of these 4 patients relapsed 6 and 14 months after cessation of TCZ, respectively. Both patients restarted TCZ and were in remission in June 2013.
Conclusions TCZ was effective on preventing relapses of AOSD. Prospective, larger study is needed for further investigation.
Yamaguchi M, et al. J Rheumatol 1992;19:424.
Disclosure of Interest : N. Nishina: None declared, Y. Kaneko: None declared, H. Kameda Grant/research support: Chugai Pharmaceutical Co., Ltd., T. Takeuchi Grant/research support: Chugai Pharmaceutical Co., Ltd., Consultant for: Chugai Pharmaceutical Co., Ltd.