What is the recommended management for systemic Still’s disease (adult‑onset Still’s disease)?

Management of Adult-Onset Still's Disease (Still's Disease)

Start an IL-1 inhibitor (anakinra or canakinumab) or IL-6 inhibitor (tocilizumab) as early as possible once the diagnosis is established, combined with short-duration glucocorticoids, to achieve drug-free remission. 1

Treatment Strategy Framework

Immediate Goals: Treat-to-Target Approach

The management follows a strict treat-to-target (T2T) strategy with defined milestones 1:

Day 7 targets:

• Complete resolution of fever
• CRP reduction by >50% 1

Week 4 targets:

• No fever present
• Active/swollen joint count reduced by >50%
• Normal CRP
• Physician and patient global assessment <20 on 0-100 visual analog scale 1

Month 3 target:

• Clinically inactive disease (CID) with glucocorticoids ≤0.1-0.2 mg/kg/day 1

Month 6 target:

• CID without any glucocorticoids 1

Ultimate goal:

• Drug-free remission (CID maintained for ≥6 months off all therapy) 1

First-Line Therapy: Biologic DMARDs

IL-1 or IL-6 inhibitors should be prioritized and initiated early to avoid prolonged systemic glucocorticoid use, as these agents have the highest level of evidence for efficacy and safety 1, 2. The 2024 EULAR/PReS guidelines explicitly state these biologics should be started "as early as possible when the diagnosis is established" 1.

Specific agents with evidence:

• Anakinra (IL-1 receptor antagonist): Daily subcutaneous injection 3
• Canakinumab (IL-1β monoclonal antibody): FDA-approved for AOSD, administered every 4 weeks 3, 4
• Tocilizumab (IL-6 receptor inhibitor): Approved for systemic juvenile idiopathic arthritis with extensive evidence 3

Glucocorticoid Management

Glucocorticoids should be used for short duration only as bridging therapy while biologics take effect 1. The goal is rapid tapering:

• Initial dosing for acute systemic manifestations (high-dose may be needed for severe features like pericarditis) 2
• Taper to ≤0.1-0.2 mg/kg/day by month 3 1
• Complete discontinuation by month 6 1

Critical pitfall: Prolonged glucocorticoid monotherapy leads to significant morbidity and should be avoided 1.

Conventional Synthetic DMARDs

Methotrexate and other conventional DMARDs (gold, azathioprine, leflunomide) have historically been used primarily for articular manifestations but are not recommended as first-line for systemic disease given the superior efficacy of biologics 3, 5. They may have a role in chronic articular patterns after systemic features are controlled.

Monitoring and Adjustment

Disease activity must be assessed regularly with dynamic adjustment of therapy (step-up or step-down) 1. While specific composite measures like sJADAS exist, the guidelines provide pragmatic clinical criteria for the targets listed above 1.

Important consideration: IL-6 inhibitors may blunt CRP elevation, so clinical assessment becomes paramount when using tocilizumab 1.

Biologic Tapering Strategy

Do not attempt biologic tapering until:

• CID maintained for 3-6 months without glucocorticoids 1
• This conservative approach minimizes flare risk

Life-Threatening Complications Requiring Immediate Action

Macrophage Activation Syndrome (MAS)

MAS is the most severe complication occurring in up to 23% of patients with high mortality 1, 6, 4. It can occur at disease onset, during treatment, or even during remission (especially with concurrent infection) 1, 6.

MAS treatment requires:

• High-dose glucocorticoids
• IL-1 inhibitors
• Ciclosporin
• Interferon-γ inhibitors 1

Maintain constant vigilance: Monitor with adequate laboratory workups and be prepared to rapidly adjust treatment 1.

Severe Lung Disease

A recently recognized complication in Still's disease patients requires:

• Screening with chest imaging and pulmonary function tests (pulse oximetry, DLCO) in symptomatic patients 1
• High-resolution CT scan for investigation 1
• T cell-directed immunosuppressants for treatment 1

Important: Presence of lung disease risk factors or active lung disease is not a contraindication to IL-1 or IL-6 inhibitors 1.

Refractory Disease Management

Difficult-to-treat patients should be managed in collaboration with Still's disease expert centers 1. This includes:

• Patients not achieving targets at specified timepoints
• Those with severe MAS
• Those with lung disease complications 1

Shared Decision-Making

All treatment targets and therapeutic strategies must be based on shared decision-making between patients and the treating team 1. This is particularly important given the chronic nature of therapy and the goal of eventual drug-free remission.

Key Clinical Pitfalls to Avoid

1. Delaying biologic therapy: Early initiation improves outcomes and shortens time to remission 3
2. Prolonged glucocorticoid monotherapy: Leads to significant toxicity without addressing underlying pathophysiology 1
3. Missing MAS: Requires high index of suspicion with persistent fever, hepatosplenomegaly, cytopenias, and hyperferritinemia 7, 6
4. Requiring arthritis for diagnosis: Arthralgia alone is sufficient; arthritis typically appears later (median 1 month delay) 1, 6
5. Inadequate monitoring: Regular assessment is essential for T2T approach 1