What is the recommended treatment regimen for adult-onset Still disease?

Treatment of Adult-Onset Still's Disease

IL-1 or IL-6 inhibitors should be initiated as early as possible once the diagnosis is established, combined with short-term glucocorticoids that are rapidly tapered, with the ultimate goal of achieving drug-free remission through a treat-to-target approach. 1

First-Line Treatment Strategy

The 2024 EULAR/PRES guidelines fundamentally changed the treatment paradigm for AOSD by prioritizing biologic DMARDs over conventional approaches 1:

Biologic DMARDs (Preferred Initial Therapy)

• IL-1 inhibitors (anakinra, canakinumab, or rilonacept) are the preferred first-line biologics

  • Anakinra has the most reassuring safety profile with lowest rates of serious adverse events (10.4 per 100 patient-years vs 36.5 for tocilizumab) 1
  • Effective for both systemic and joint manifestations
  • Can be used as primary therapy in moderate-to-severe disease 2

• IL-6 inhibitors (tocilizumab) are an alternative first-line option

  • Higher rates of infectious adverse events compared to IL-1 inhibitors (104.6 vs 94.5 per 100 patient-years) 1
  • May be preferred in patients with prominent joint involvement 3

Glucocorticoid Use (Minimize and Taper)

Critical caveat: While glucocorticoids are still widely used in practice (97.7% of patients in real-world data 4), the guidelines strongly emphasize limiting their use 1:

• Short-term high-dose glucocorticoids may be necessary at disease onset, particularly with severe symptoms or impending macrophage activation syndrome (MAS)
• Some patients may not require glucocorticoids at all when IL-1 or IL-6 inhibitors can be initiated immediately 1
• Glucocorticoid dependence must be avoided—if GCs are needed to maintain disease control, add other therapies rather than continuing steroids 1
• Long-term glucocorticoid use causes severe side effects including metabolic syndrome 1

Treatment Algorithm

Step 1: Initial Therapy

1. Start IL-1 inhibitor (preferably anakinra) OR IL-6 inhibitor (tocilizumab)
2. Add short-term glucocorticoids only if severe symptoms, impending MAS, or severe pericarditis
3. Begin rapid glucocorticoid taper as soon as disease control achieved

Step 2: If Inadequate Response to IL-1 Inhibitor

• Switch to IL-6 inhibitor, particularly if prominent joint involvement 3
• Alternative: Try different IL-1 inhibitor 3

Step 3: If Inadequate Response to IL-6 Inhibitor

• Switch to IL-1 inhibitor if not previously tried
• Consider TNF inhibitors as further option in patients with prominent joint involvement 3

Step 4: Conventional Synthetic DMARDs (Limited Role)

Important limitation: Methotrexate was not superior to placebo in the only RCT performed 1

Use csDMARDs only when:

• IL-1 and IL-6 inhibitors are unavailable 1
• Predominant arthritis at onset with inadequate response to glucocorticoids 3
• As glucocorticoid-sparing agents (though biologics are preferred) 1

Options include:

• Methotrexate
• Cyclosporin A (particularly useful in MAS risk) 1

Step 5: Achieving Remission

• Once sustained clinical and laboratory remission achieved, consider drug tapering or discontinuation 3
• Ultimate goal is drug-free remission, which is realistic for substantial proportion of patients 1

Treat-to-Target Approach

Apply dynamic treatment adjustments based on disease activity 1:

• Regularly assess disease activity
• Step-up therapy if inadequate control
• Step-down therapy once remission achieved
• Sequential therapeutic targets with ultimate goal of drug-free remission

Critical Complications Requiring Immediate Action

Macrophage Activation Syndrome (Life-Threatening)

This is the main life-threatening complication that can occur at onset, during treatment, or even in remission 1:

• Monitor with adequate biological workups continuously
• If MAS develops: High-dose glucocorticoids PLUS anakinra, ciclosporin, and/or IFNγ inhibitors as initial therapy 1
• Can present as disease relapse, especially with concurrent infection 1

Lung Disease

• Actively screen with clinical symptoms (clubbing, persistent cough, dyspnea) and pulmonary function tests 1
• Investigate with high-resolution CT if symptoms present
• Important: Lung disease is NOT a contraindication to IL-1 or IL-6 inhibitors 1

Real-World Practice Gap

Major pitfall: Real-world data shows significant non-compliance with guidelines 4:

• Glucocorticoids still used in 97.7% of patients (should be minimized)
• Biologics administered early (within 3 months) in only minority of patients (should be initiated immediately)
• This gap between recommendations and practice may result in worse outcomes and unnecessary glucocorticoid toxicity

NSAIDs

Limited to symptomatic treatment of fever and arthralgia during diagnostic workup only—no evidence supporting efficacy for disease control 1