Treatment of Adult-Onset Still's Disease (AOSD)
The first-line treatment for Adult-Onset Still's Disease should be IL-1 inhibitors (such as anakinra) or IL-6 receptor inhibitors (such as tocilizumab), as these biologics show the highest level of evidence for efficacy and safety in managing AOSD. 1
Disease Patterns and Treatment Approach
AOSD typically follows one of three clinical patterns, each affecting approximately one-third of patients 1:
- Self-limited/monocyclic pattern: Characterized by systemic symptoms with remission within 1 year (median 9 months) 1
- Intermittent/polycyclic pattern: Recurrent flares with complete remission between episodes 1
- Chronic articular pattern: Dominated by joint manifestations that can lead to severe joint destruction 1
Treatment Algorithm
Initial Treatment
For active AOSD with high disease activity:
- Start with IL-1 inhibitors (anakinra) or IL-6 receptor inhibitors (tocilizumab) 1
- May combine with high-dose glucocorticoids (≥1 mg/kg/day prednisone equivalent) initially, with rapid tapering once improvement begins 1
- Anakinra is preferred for patients with impending macrophage activation syndrome (MAS) 1
For AOSD with moderate disease activity:
- IL-1 inhibitors or IL-6 receptor inhibitors with low-dose glucocorticoids (≤0.1 mg/kg/day prednisone equivalent) 1
Traditional Treatment Approach (Less Effective)
- NSAIDs: Only effective as monotherapy in 7-15% of patients 1
- Glucocorticoids: Historically the mainstay of treatment with 76-95% response rates, but most patients require long-term maintenance with significant side effects 1
- Conventional DMARDs (particularly methotrexate): Used as steroid-sparing agents with modest efficacy (approximately 40% overall response) 1
Treatment Targets and Monitoring
- Primary target: Clinically inactive disease (CID) off glucocorticoids 1
- Intermediate targets:
- Resolution of fever
- Decrease of active joints by 50% 1
- Monitoring: Regular assessment of disease activity with adjustment of therapy accordingly 1
Management of Refractory Disease
- If no response to initial biologic therapy, rotate between IL-1 and IL-6 inhibitors 1
- For difficult-to-treat cases, consult with specialized centers 1
- Experimental therapies (JAK inhibitors, IFN-γ inhibitors) may be considered for refractory cases 1
Management of Complications
Macrophage Activation Syndrome (MAS)
- Most severe complication with high mortality rate 2
- Treatment includes:
Lung Disease
- Screen for symptoms (clubbing, persistent cough, shortness of breath) 1
- Monitor with pulmonary function tests and high-resolution CT when indicated 1
- IL-1 or IL-6 inhibitors are not contraindicated in patients with lung disease 1
Evidence for Biologic Therapies
IL-1 inhibitors (anakinra, canakinumab):
IL-6 receptor inhibitors (tocilizumab):
Important Considerations
- Early initiation of biologic therapy improves outcomes ("window of opportunity") 3
- Treatment should follow a treat-to-target approach with regular disease activity assessment 1
- Maintain clinically inactive disease for at least 6 months off glucocorticoids before considering tapering of biologic therapy 1
- Patients with chronic articular disease generally have worse prognosis and may require more aggressive therapy 1
Pitfalls to Avoid
- Relying solely on NSAIDs or glucocorticoids as long-term therapy, as most patients will require more advanced treatment 1
- Delaying biologic therapy in patients not responding to conventional treatments 3
- Failing to screen for and promptly treat MAS, which is the most life-threatening complication 1, 2
- Overlooking the need for regular monitoring of disease activity and treatment response 1