What is the treatment for Still's disease?

Treatment of Still's Disease

IL-1 inhibitors (anakinra) or IL-6 inhibitors (tocilizumab) should be initiated as early as possible when Still's disease is diagnosed, as these biologics have the strongest evidence for controlling both systemic and articular manifestations while minimizing glucocorticoid exposure. 1

First-Line Treatment Strategy

Biologic therapy should be prioritized over traditional approaches:

• IL-1 inhibitors (anakinra, canakinumab, rilonacept) or IL-6 inhibitors (tocilizumab) are the recommended first-line disease-modifying agents based on overwhelming real-world evidence and favorable benefit-risk profiles 1, 2
• Among IL-1 inhibitors, anakinra has the most reassuring safety profile with lower rates of serious adverse events (10.4 per 100 patient-years) compared to tocilizumab (36.5 per 100 patient-years) 1
• Early initiation (within 3 months of symptom onset) improves outcomes and may prevent chronic persistent disease course 1

Role of Glucocorticoids

Glucocorticoids should be used only as bridging therapy, not maintenance:

• Initial doses of 0.8-1 mg/kg/day prednisone may be needed for severe systemic features, but the goal is complete discontinuation 1
• Glucocorticoid dependence is unacceptable—if GCs are needed to maintain disease control, biologic therapy must be added or escalated 1
• Pulse methylprednisolone (5 mg/kg/day for 3 days) can be used for severe presentations but offers no long-term advantage over oral prednisone 1

Treatment Targets and Timeline

Follow a treat-to-target approach with specific milestones:

• Day 7: Resolution of fever and CRP reduction >50% 1
• Week 4: No fever, >50% reduction in active joint count, normal CRP 1
• Month 3: Clinically inactive disease (CID) with glucocorticoids <0.1-0.2 mg/kg/day 1
• Month 6: CID without glucocorticoids 1
• Ultimate goal: Drug-free remission (CID maintained ≥6 months off all therapy) 1

Second-Line and Alternative Agents

When biologics are unavailable or fail:

• Methotrexate (MTX) can be used as a glucocorticoid-sparing agent, though it failed to show superiority over placebo in the only RCT 1
• MTX at 11.5 mg/week allowed prednisone tapering in 85% of patients in observational studies 1
• Conventional DMARDs (hydroxychloroquine, gold, azathioprine) have approximately 40% overall response rates and should only be considered where biologics are unavailable 1
• NSAIDs alone control disease in only 7-15% of patients and should be limited to symptomatic management during diagnostic workup 1, 2

Switching Between Biologics

If initial biologic fails:

• Rotate between IL-1 and IL-6 inhibitors—they target different pathways and may have complementary efficacy 1
• Infliximab may be more effective than etanercept for TNF inhibition, though anti-TNF agents are generally less effective than IL-1/IL-6 blockade 1

Management of Macrophage Activation Syndrome (MAS)

MAS is a life-threatening complication requiring immediate recognition:

• Suspect MAS with: persistent fever, splenomegaly, rising ferritin, falling cell counts, abnormal liver function, elevated triglycerides 1
• Treatment requires high-dose glucocorticoids PLUS anakinra (>4 mg/kg/day or 100 mg twice daily in adults) 1, 2
• Consider adding cyclosporine and/or IFN-γ inhibitors as part of initial MAS therapy 1

Management of Lung Disease

Active screening is essential:

• Screen for clubbing, persistent cough, shortness of breath with pulmonary function tests (pulse oximetry, DLCO) 1
• Investigate with high-resolution CT if symptoms present 1
• IL-1 or IL-6 inhibitors are NOT contraindicated in patients with lung disease 1, 2

Common Pitfalls to Avoid

• Do not maintain patients on chronic glucocorticoids—this represents treatment failure requiring biologic escalation 1
• Do not delay biologic therapy—the therapeutic window of opportunity closes after 3 months 1
• Do not rely on NSAIDs or conventional DMARDs as primary therapy when biologics are available 1, 2
• Do not miss MAS—it can develop at any point and requires immediate aggressive treatment 1
• Refer difficult-to-treat patients, those with severe MAS, or lung disease to Still's disease expert centers 1