What is Adult-Onset Still's Disease (AOSD)?

From the Guidelines

Still disease, also known as adult-onset Still's disease (AOSD), is a rare inflammatory disorder that should be treated with IL-6 inhibitors, such as tocilizumab, as the first-line biologic agent, given its high efficacy and safety profile, as demonstrated in recent studies 1.

Overview of Still Disease

Still disease is characterized by high spiking fevers, salmon-pink rash, arthritis, and multi-organ involvement. The disease follows a monocyclic (single episode), polycyclic (recurrent flares), or chronic pattern, with arthritis often being the most persistent symptom requiring ongoing management.

Treatment Approach

Treatment typically begins with NSAIDs like naproxen (500mg twice daily) or ibuprofen (600-800mg three times daily) for mild cases, though most patients require stronger medications. Glucocorticoids such as prednisone (0.5-1mg/kg/day) are often needed for moderate to severe disease. For steroid-sparing and long-term management, conventional DMARDs like methotrexate (15-25mg weekly) or biologic agents targeting IL-1 (anakinra 100mg daily or canakinumab 4mg/kg every 4 weeks) or IL-6 (tocilizumab 8mg/kg IV every 2-4 weeks) are used.

Recent Evidence on IL-6 Inhibitors

Recent studies, including a systematic review informing the EULAR/PRES guidelines for the management of Still's disease, have demonstrated the efficacy and safety of IL-6 inhibitors, such as tocilizumab, in the treatment of AOSD and sJIA 1. The use of tocilizumab has been associated with significant improvements in clinical outcomes, including reductions in fever, arthritis, and systemic features, as well as improvements in quality of life.

Monitoring and Management

Treatment should be individualized based on disease severity, with close monitoring for complications including macrophage activation syndrome, which presents with worsening fevers, cytopenias, liver dysfunction, and coagulopathy. Regular assessments of disease activity, laboratory parameters, and adverse events are crucial to optimize treatment outcomes and minimize potential side effects.

Key Considerations

• The use of IL-6 inhibitors, such as tocilizumab, as the first-line biologic agent in the treatment of AOSD and sJIA, given its high efficacy and safety profile 1.
• Individualized treatment approaches based on disease severity and patient characteristics.
• Close monitoring for complications, including macrophage activation syndrome, and regular assessments of disease activity and laboratory parameters.

From the Research

Overview of Still Disease

• Still disease, also known as Adult-Onset Still's Disease (AOSD), is a rare systemic inflammatory condition characterized by high spiking fever, evanescent rash, and polyarthritis 2, 3, 4.
• The disease can range from self-limiting forms with mild symptoms to life-threatening cases 2.

Clinical Manifestations and Diagnosis

• The clinical presentation of AOSD is highly variable, accompanied by a broad spectrum of disease manifestations 4.
• AOSD patients may experience various life-threatening complications, such as macrophage activation syndrome, which is reported in as high as 23% of AOSD patients 4.
• The ambiguity in presentation and lack of serologic markers make the diagnosis of AOSD difficult, often leading to a delay in diagnosis 4.
• The Yamaguchi and Fautrel criteria are the most widely used diagnostic tools in clinical practice 4.

Treatment Options

• The current AOSD treatment paradigm includes non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids initially, conventional synthetic disease-modifying anti-rheumatic drugs in steroid-refractory patients, and biologics in those resistant to conventional treatment 2, 4.
• Biologic agents such as IL-1, IL-6, and tumor necrosis factor-α antagonists have shown efficacy in certain subsets of patients with AOSD 2, 3, 5.
• Tocilizumab, an IL-6 antagonist, has been shown to be an effective treatment option for refractory AOSD patients 6, 5.
• Canakinumab is the only FDA-approved biologic for the treatment of AOSD 4.

Efficacy and Safety of Treatment Options

• Non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids are effective in controlling clinical manifestations in the majority of AOSD patients 2.
• Conventional DMARDs can be effective in some severe and steroid-dependent cases of AOSD; however, anti-cytokine agents represent an effective and overall more suitable alternative in this specific subset of patients 2.
• IL-1 blockade has an excellent safety profile and represents the first choice of biologic treatment in AOSD patients 2.
• Tocilizumab has been shown to be well-tolerated and effective in treating refractory AOSD patients 6, 5.