A Pilot Study on Tocilizumab for Treating Refractory Adult-Onset Still’s Disease

Abstract

To investigate the efficacy and safety of Tocilizumab (TCZ) in patients with refractory adult-onset Still’s disease (AOSD). We enrolled 8 female patients from October 2013 to July 2014. All patients fulfilled Japan’s Yamaguch AOSD classification and recognized as refractory AOSD. All Patients received TCZ treatment 4–8 mg/kg every 4 weeks. Evaluation of efficacy was conducted after 3 months and 6 months, including clinical manifestations of AOSD patients, improvement of inflammatory markers as well as glucocorticoids dosage adjustments. Treatment-related adverse events were also recorded. Patients treated with Tocilizumab with average age 41.1 years old, the average disease duration 23.6 months. Two patients drop off due to infusion side effects. Others were followed at least 6 months. After 3 months of follow-up, remission rates of fever, arthritis and rashes from 8 patients were 87.5%, 100% and 87.5%. White blood cell counts, erythrocyte sedimentation rate, C-reactive protein and ferritin levels were decreased (P < 0.01) significantly compared to treatment before. Furthermore, the average dose of prednisone was reduced from 51.7 ± 38.4 mg/d to 12.9 ± 7.7 mg/d (P < 0.01). Our findings suggest that tocilizumab could alleviate the clinical manifestations of refractory AOSD rapidly and efficiently.

The Two-Faced Cytokine IL-6 in Host Defense and Diseases

“…It is characterized by elevated levels of inflammatory cytokines in serum including IL-6, IL-18, IL-1, TNFα and IFNγ. An increasing number of case reports or series has shown the effectiveness of TCZ on AOSD and reduction of glucocorticoid dose [ 117 , 118 , 119 ]. A meta-analysis of 10 studies with 147 patients showed that TCZ therapy achieved a partial remission rate in 85.38% and complete remission rate in 77.91%, and even in patients with refractory cases, the remission rate was 87.92% [ 120 ], suggesting a promising effect of TCZ on AOSD.…”

Tofacitinib in refractory adult-onset Still’s disease: 14 cases from a single centre in China

“…In our study, we aim to describe, to our knowledge for the first time, the efficacy of tofacitinib in 14 patients with refractory AOSD. All patients fulfilled Yamaguchi’s criteria and were classified as refractory AOSD as defined previously 6. They were followed up for the shortest of 1 month and the longest for 24 months by the same medical team.…”

Efficacy of Denosumab for Osteoporosis in Two Patients with Adult-Onset Still’s Disease—Denosumab Efficacy in Osteoporotic Still’s Disease Patients

“…Karmakar et al reported that IL-17 promoted bone erosion in a murine collagen-induced arthritis model by upregulating the expression of RANKL and RANK, thereby enhancing osteoclastogenesis [ 11 ]. Li et al recently found that the IL-6 receptor monoclonal antibody, tocilizumab, exerted a favorable effect on recurrent AOSD [ 12 ]. These findings suggest that the RANK/RANKL pathway represents a pathogenic mechanism of bone erosion and/or destruction in arthritic diseases, including AOSD.…”

“…These findings suggest that the RANK/RANKL pathway represents a pathogenic mechanism of bone erosion and/or destruction in arthritic diseases, including AOSD. We and others have found denosumab to be useful for GIO patients [ 8 , 12 , 13 , 14 , 15 ]. Although BPs are first-line drugs for GIO, the current patients exhibited upper gastrointestinal issues that precluded BP use.…”