Tocilizumab in refractory adult Still's disease

Abstract

Objective. There is an unmet need for the treatment of adult Still's disease (ASD), the pathogenesis of which may involve interleukin-6 (IL-6). We report the first series of patients with ASD treated with tocilizumab (TCZ), a humanized anti-IL-6 receptor antibody. Methods. All ASD patients treated with TCZ in France between July 2006 and July 2009 after failure to all available therapies were included in this cohort study. The main outcome measures were the European League Against Rheumatism (EULAR) improvement criteria and resolution of systemic symptoms at the 3-and 6-month followup periods. Results. Fourteen patients with refractory ASD were included. At the start of TCZ treatment, despite a mean prednisone dosage of 23.3 mg/day, based on a 28-joint count, mean tender joints were 10.5, mean swollen joints were 7.9, and the mean Disease Activity Score in 28 joints was 5.61. Recurrent systemic involvement, including fever and rash, was present in 7 patients. TCZ was administered at 5-8 mg/kg every 2 or 4 weeks (8 mg/kg/month, n ‫؍‬ 9). Eleven patients successfully completed the 6-month study; 1 withdrew due to necrotizing angiodermatitis, another due to chest pain at each TCZ infusion, and a third due to systemic flare. A good EULAR response was observed in 64% of patients (9 of 14) at 3 months and EULAR remission was observed in 57% (8 of 14) at 6 months. Systemic symptoms were resolved in 86% of patients (6 of 7). Moreover, corticosteroid dose was reduced by 56%. No other severe adverse effects occurred. Conclusion. TCZ is a promising new treatment for ASD.

Efficacy of Tocilizumab in Conventional Treatment–Refractory Adult‐Onset Still's Disease: Multicenter Retrospective Open‐Label Study of Thirty‐Four Patients

“…In keeping with previous series (8,14), a high number of our patients had received other synthetic immunosuppressive agents (Table 1). Moreover, in many of these patients, AOSD had also been refractory to treatment with biologic agents such as anakinra or anti-TNF␣ ( Table 1).…”

“…Moreover, in many of these patients, AOSD had also been refractory to treatment with biologic agents such as anakinra or anti-TNF␣ ( Table 1). As in our series, the patients described by Puechal et al (8) and Elkayam et al (14) received variable dosages of TCZ (4-8 mg/kg every 2, 4, or 8 weeks). In this regard, although the dosage of TCZ in RA or systemic JIA is well established (6,7), there is no consensus on the dosage of TCZ that should be given to patients with AOSD.…”

“…To the best of our knowledge, 2 small series of patients with conventional treatment-refractory AOSD who received therapy with TCZ have been reported. One of these studies assessed 14 patients (8), and the other assessed 11 patients (14). In both series, the patients were followed up for 6 months.…”

“…Because IL-6 has been implicated in the pathogenesis of AOSD (3), several studies have assessed the potential effect of TCZ in patients with AOSD refractory to multiple therapies (8)(9)(10). However, in most cases, information related to this issue is based on small series or case reports.…”

Targeting Interleukin-6 in Rheumatoid Arthritis

“…There are also case reports in regards to the use of tocilizumab in other auto-immune conditions such as giant cell arteritis [30,31], adult onset Still's disease [32] , systemic lupus erythematosus [33], ANCA-associated vasculitis [34], Behcet's disease [35,36], systemic sclerosis [37] and polymyositis [38]. These reports showed that tocilizumab was the salvage therapy used after disease resistance to various former drugs.…”