Background Adult-onset Still's disease (AOSD) is a systemic inflammatory disease of unknown etiology. Corticosteroids still provide mainstay AOSD therapy despite various adverse effects. Recently, AOSD patients have been successfully treated with anti-cytokine therapies such as with TNF-α blocking agents, an IL-1 receptor antagonist, and an anti-IL-6 receptor monoclonal antibody. Among these case reports, TCZ seems to be highly effective for treating patients refractory to TNF antagonists and IL-1 antagonist.
Objectives To assess the efficacy and safety of tocilizumab (TCZ) monotherapy for the induction therapy of adult onset Still's disease (AOSD) in a prospective single-arm, single-center, cohort, pilot study.
Methods Seven AOSD patients (male 2, female 5) who had agreed with our prospective trial since April 2010 till May 2015 were enrolled. Our study protocol is that patients received 8 mg/kg of intravenous TCZ fortnightly for the first two months (five courses), then monthly for the next 5 months and after that they stop TCZ therapy and we monitor symptoms about AOSD relapses. In this report, we evaluated the efficacy and safety in 52 week. Efficacy was evaluated by serum markers (WBC, CRP and serum ferritin), clinical symptoms and ratio of patients who required additional therapy, and safety was evaluated by adverse events for 52 week.
Results The mean age was 41.4. The ratio of fever, arthralgia, rash and sore throat are 100% (n=7/7), 100% (n=7/7), 85.7% (n=6/7) and 71.4% (n=5/7) respectively. LOCF analysis revealed that WBC, CRP and serum ferritin level decreased significantly from 14757±4667/μl to 6985±2903/μl, from 13.4±7.1mg/dl to 0.3±0.6mg/dl and from 6927±5376ng/ml to 2416±5589ng/ml at month 7 (TCZ final infusion) respectively (each, P<0.01). The improvement rate of fever, arthralgia and eruption were 100% (n=7/7), 85.7% (n=6/7) and 85.7% (n=6/7) respectively at month 7. One patient couldn't continue TCZ therapies because of lack of efficacy (14.3%, n=1) and required additional therapy (prednisolone) at week 2. Another patient also abandoned this trial due to adverse event (14.3%, n=1, urinary tract infection). The other 5 patients could complete the 7-month course of the study and had no symptoms at month 7. Four of five patients had no flare-up signs until month 5 after stopping TCZ. One patient had relapse symptoms such as rash and arthralgia and increased serum level of CRP and serum ferritin at month 2 after final TCZ infusion. There were no serious adverse events during the course of the trial.
Conclusions TCZ monotherapy can be an alternative treatment strategy for AOSD in some patients.
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Disclosure of Interest T. Kondo: None declared, Y. Okada: None declared, A. Shibata: None declared, K. Chino: None declared, T. Kurasawa: None declared, A. Okuyama: None declared, H. Takei: None declared, K. Amano Grant/research support from: Chugai Pharmaceutical Co.Ltd.