What is the initial treatment for Still's Disease?

Initial Treatment for Still's Disease

An IL-1 inhibitor (preferably anakinra) or an IL-6 inhibitor (tocilizumab) should be initiated as early as possible—ideally within 3 months of symptom onset—when the diagnosis of Still's disease is established. 1

Treatment Priority and Rationale

The 2024 EULAR/PReS guidelines fundamentally changed the treatment paradigm for Still's disease by prioritizing biologic therapy over traditional approaches. IL-1 and IL-6 inhibitors are now the treatment of choice, not glucocorticoids or conventional DMARDs. 1

Why Biologics First?

• Window of opportunity exists: Real-life data demonstrate that initiating IL-1 or IL-6 inhibitors before 3 months from symptom onset achieves higher rates of clinically inactive disease off glucocorticoids and may prevent chronic persistent disease patterns. 1
• Superior efficacy: These biologics control both systemic manifestations (fever, rash, serositis) and articular disease, while dramatically reducing glucocorticoid exposure. 1
• Favorable safety profile: The benefit-risk balance is extremely favorable, with these agents proven safe even in critically ill patients with sepsis and severe COVID-19. 1

Specific Biologic Selection

Among the biologics, anakinra (an IL-1 inhibitor) has the most reassuring safety profile and should be preferred in most cases. 1

Safety Comparison Data:

• Anakinra: 10.4 serious adverse events per 100 patient-years, 18.1 infectious adverse events per 100 patient-years 1
• Tocilizumab (IL-6 inhibitor): 36.5 serious adverse events per 100 patient-years, 104.6 infectious adverse events per 100 patient-years 1
• Canakinumab: 38.9 serious adverse events per 100 patient-years, 190.2 infectious adverse events per 100 patient-years 1

Anakinra is specifically preferred when macrophage activation syndrome (MAS) is impending or present, as it can be used at high doses (>4 mg/kg/day in children or 100 mg twice daily in adults) for this life-threatening complication. 2

Role of Traditional Therapies

NSAIDs

• Use only as symptomatic treatment during diagnostic workup to manage fever and arthralgia. 1
• No RCT evidence supports efficacy in Still's disease, and monotherapy controls disease in only 7-15% of patients. 1

Glucocorticoids

• Should NOT be used as maintenance therapy to achieve treatment targets. 1
• May be used briefly at low doses (≤0.1-0.2 mg/kg/day prednisone equivalent) during biologic initiation, but the goal is rapid withdrawal. 1
• Glucocorticoid dependence mandates adding or switching biologics rather than continuing steroids. 1

Conventional DMARDs (Methotrexate)

• Not recommended as initial therapy. 1
• The only RCT of methotrexate in systemic juvenile idiopathic arthritis showed no superiority over placebo. 1
• Should be considered only in countries where IL-1 and IL-6 inhibitors are unavailable. 1

Treatment Targets and Timeline

The treat-to-target approach requires achieving specific milestones: 1

• Day 7: Resolution of fever and CRP reduction >50% 1
• Week 4: No fever, active joint count reduced >50%, normal CRP 1
• Month 3: Clinically inactive disease with glucocorticoids <0.1-0.2 mg/kg/day 1
• Month 6: Clinically inactive disease WITHOUT glucocorticoids 1

Clinically inactive disease (CID) is defined as absence of Still's disease-related symptoms with normal ESR or CRP. 1, 3

Critical Pitfalls to Avoid

Delayed Biologic Initiation

The most common error is treating Still's disease like other rheumatic conditions by starting with NSAIDs, then glucocorticoids, then DMARDs, and only using biologics as "last resort" therapy. This approach is outdated and leads to worse outcomes, including chronic persistent disease patterns. 1

Glucocorticoid Dependence

Never maintain patients on glucocorticoids to control disease activity. If disease control requires ongoing steroids, this represents treatment failure requiring biologic initiation or switching. 1

Missing MAS

Macrophage activation syndrome occurs in up to 23% of patients and can develop at any time—even during remission. Maintain high vigilance and monitor for persistent fever, splenomegaly, rising ferritin, cytopenias, abnormal liver function, and elevated triglycerides. 1, 3

Special Considerations

Lung Disease

The presence of lung disease or risk factors for Still's lung disease is NOT a contraindication to IL-1 or IL-6 inhibitors. 1 Screen actively for clubbing, persistent cough, and shortness of breath, and investigate with high-resolution CT when symptoms are present. 1

Resource-Limited Settings

In countries where biologics are unavailable, conventional DMARDs (particularly methotrexate) can be used as glucocorticoid-sparing agents, though efficacy is modest. 1