Tocilizumab in patients with adult-onset still’s disease refractory to glucocorticoid treatment: a randomised, double-blind, placebo-controlled phase III trial

Abstract

ObjectiveTo evaluate the efficacy and safety of tocilizumab, an interleukin-6 receptor antibody, in patients with adult-onset Still’s disease.MethodsIn this double-blind, randomised, placebo-controlled phase III trial, 27 patients with adult-onset Still’s disease refractory to glucocorticoids were randomised to tocilizumab at a dose of 8 mg/kg or placebo given intravenously every 2 weeks during the 12-week, double-blind phase. Patients received open-label tocilizumab for 40 weeks subsequently. The primary outcome was American College of Rheumatology (ACR) 50 response at week 4. The secondary outcomes included ACR 20/50/70, systemic feature score, glucocorticoid dose and adverse events at each point.ResultsIn the full analysis set, ACR50 response at week 4 was achieved in 61.5% (95% CI 31.6 to 86.1) in the tocilizumab group and 30.8% (95% CI 9.1 to 61.4) in the placebo group (p=0.24). The least squares means for change in systemic feature score at week 12 were –4.1 in the tocilizumab group and –2.3 in the placebo group (p=0.003). The dose of glucocorticoids at week 12 decreased by 46.2% in the tocilizumab group and 21.0% in the placebo group (p=0.017). At week 52, the rates of ACR20, ACR50 and ACR70 were 84.6%, 84.6% and 61.5%, respectively, in both groups. Serious adverse events in all participants who received one dose of tocilizumab were infections, aseptic necrosis in the hips, exacerbation of adult-onset Still’s disease, drug eruption and anaphylactic shock.ConclusionThe study suggests that tocilizumab is effective in adult-onset Still’s disease, although the primary endpoint was not met and solid conclusion was not drawn.

Adult-onset Still’s disease biological treatment strategy may depend on the phenotypic dichotomy

“…The efficacy of these medications in AOSD is controversial, but some studies suggest that they have a place in the treatment of the chronic articular form [31][32][33], while others have showed rather disappointing results [19,20,34]. The excellent efficacy and clear steroid-sparing effect of tocilizumab determined in our study, concurring with the findings of a recent meta-analysis showing that AOSD patients treated with tocilizumab had a pooled remission rate of approximately 85% regardless of the phenotype [35], and of the first RCT investigating tocilizumab in AOSD [36], should make clinicians prioritize tocilizumab to anti-TNF blockers for patients with a chronic articular form of AOSD. Canakinumab showed some inconsistent results in AOSD [37][38][39] but is currently being investigated for its efficacy on AOSD's joint involvement (NCT02204293).…”

Translating IL-6 biology into effective treatments

“…AOSD and sJIA are increasingly considered to be the same disease, with AOSD occurring in adulthood and sJIA in childhood. In a double-blind RCT of 27 patients with AOSD refractory to treatment with glucocorticoids, an ACR50 response (reflecting 50% improvement) at week 4 was achieved in ~61% of patients treated with tocilizumab, compared with ~31% of placebo-treated patients, although the difference was not statistically significant 94 . Patients in the tocilizumab group also had improvements in systemic symptoms and a decreased dose of glucocorticoids compared with the placebo group.…”

Coronavirus disease 2019 (COVID-19): a clinical update

“…Tocilizumab is a humanized IgG1k monoclonal antibody which can specifically bind soluble or membrane-type IL-6 receptors (Sil-6R and Mil-6R), and has been widely used in the treatment of autoimmune diseases such as rheumatoid arthritis [58], adult-onset Still's disease [59], and large vessel vasculitis [60]. For COVID-19 infection, clinical studies have shown that serum levels of inflammatory mediators in severe patients are significantly higher than those in common patients [22].…”