What is the treatment for Adult Onset Still's Disease (AOSD)?

Treatment of Adult-Onset Still's Disease

The American College of Rheumatology recommends IL-1 inhibitors (anakinra) or IL-6 receptor inhibitors (tocilizumab) as first-line treatment for AOSD, with the primary goal of achieving clinically inactive disease off glucocorticoids. 1

First-Line Treatment Strategy

For active AOSD with high disease activity, start with IL-1 inhibitors (anakinra) or IL-6 receptor inhibitors (tocilizumab) as these biologics show the highest level of evidence for efficacy and safety. 2

• For moderate disease activity, combine IL-1 or IL-6 inhibitors with low-dose glucocorticoids (≤0.1 mg/kg/day prednisone equivalent). 2
• Anakinra is specifically preferred when impending macrophage activation syndrome (MAS) is present, as this complication occurs in up to 23% of patients and carries high mortality. 2, 3
• Early initiation of biologic therapy improves outcomes through a "window of opportunity" effect—the earlier treatment begins, the sooner clinical inactivity can be achieved. 1, 4

Why Traditional Therapies Are Inadequate

• NSAIDs as monotherapy are effective in only 7-15% of patients and should not be relied upon for long-term management. 2
• Glucocorticoids, while historically the mainstay with 76-95% response rates, require long-term maintenance in most patients with significant side effects. 2
• Conventional DMARDs (particularly methotrexate) have modest efficacy with approximately 40% overall response and are primarily used as steroid-sparing agents, not primary therapy. 2

Treatment Targets and Monitoring

The primary treatment target is clinically inactive disease (CID) off glucocorticoids, defined as absence of Still's disease-related symptoms with normal ESR or CRP. 2, 3

• Intermediate targets include a 50% decrease in active joints. 2
• Follow a treat-to-target approach with regular disease activity assessment and therapy adjustment accordingly. 1, 2
• Maintain clinically inactive disease for at least 6 months off glucocorticoids before considering tapering of biologic therapy. 2

Management of Refractory Disease

• If no response to initial biologic therapy, rotate between IL-1 and IL-6 inhibitors. 2
• For difficult-to-treat cases, consult with specialized centers. 2
• Experimental therapies including JAK inhibitors and IFN-γ inhibitors may be considered for refractory cases. 2
• Canakinumab is the only FDA-approved biologic specifically for AOSD treatment. 5

Management of Life-Threatening Complications

Macrophage activation syndrome requires immediate recognition and aggressive treatment with high-dose glucocorticoids and high-dose anakinra (>100 mg twice daily in adults). 2

• Cyclosporine A and/or IFN-γ inhibitors may be added for MAS treatment. 2, 6
• High-dose methylprednisolone pulses, cyclosporine A, and etoposide are essential for MAS/HLH with Hscore above 150. 7
• Features distinguishing MAS from active AOSD include persistent (not spiking) fever, sharp decrease in leukocytes and platelets, further elevation of transaminases and ferritin, significant hepatosplenomegaly, CNS symptoms, and DIC. 7

Disease Pattern Considerations

AOSD follows three clinical patterns, each affecting approximately one-third of patients: 2

• Self-limited/monocyclic: Systemic symptoms with remission within 1 year (median 9 months)
• Intermittent/polycyclic: Recurrent flares with complete remission between episodes
• Chronic articular: Dominated by joint manifestations that can lead to severe joint destruction and generally requires more aggressive therapy

Monitoring for Organ Complications

• Screen for lung disease symptoms (clubbing, persistent cough, shortness of breath) with pulmonary function tests and high-resolution CT when indicated. 2
• IL-1 or IL-6 inhibitors are not contraindicated in patients with lung disease. 2
• Monitor for cardiac complications including myocarditis, which can present atypically. 8

Critical Pitfalls to Avoid

• Do not rely solely on NSAIDs or glucocorticoids as long-term therapy—most patients will require biologic treatment. 2
• Do not delay biologic therapy initiation—early treatment significantly improves outcomes. 1
• Do not miss MAS, which is the most life-threatening complication requiring immediate recognition and treatment. 2, 3
• Do not wait for arthritis to develop before making the diagnosis—arthralgia alone is sufficient per current guidelines. 3