Treatment of Adult-Onset Still's Disease (AOSD)

Introduction to AOSD Treatment

The American College of Rheumatology recommends 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, 2

AOSD typically follows one of three clinical patterns, each affecting approximately one-third of patients, including self-limited/monocyclic, intermittent/polycyclic, and chronic articular patterns 3, 4
The self-limited/monocyclic pattern is characterized by systemic symptoms with remission within 1 year (median 9 months) 3, 5
The intermittent/polycyclic pattern is characterized by recurrent flares with complete remission between episodes 5
The chronic articular pattern is dominated by joint manifestations that can lead to severe joint destruction 5

For active AOSD with high disease activity, the European League Against Rheumatism recommends starting with IL-1 inhibitors (anakinra) or IL-6 receptor inhibitors (tocilizumab) 1, 6
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) may be used 1
Anakinra is preferred for patients with impending macrophage activation syndrome (MAS) 1

NSAIDs are only effective as monotherapy in 7-15% of patients 5, 7
Glucocorticoids have historically been the mainstay of treatment with 76-95% response rates, but most patients require long-term maintenance with significant side effects 5, 7
Conventional DMARDs (particularly methotrexate) are used as steroid-sparing agents with modest efficacy (approximately 40% overall response) 8

The primary target is clinically inactive disease (CID) off glucocorticoids 1, 6
Intermediate targets include decrease of active joints by 50% 6
Regular assessment of disease activity with adjustment of therapy accordingly is recommended 6

If no response to initial biologic therapy, rotating between IL-1 and IL-6 inhibitors may be considered 1
For difficult-to-treat cases, consulting with specialized centers is recommended 1, 6
Experimental therapies (JAK inhibitors, IFN-γ inhibitors) may be considered for refractory cases 1, 2

High-dose glucocorticoids and high-dose anakinra (>4 mg/kg/day in children or 100 mg twice daily in adults) are used to treat macrophage activation syndrome (MAS) 1, 6
Cyclosporine A and/or IFN-γ inhibitors may be considered for MAS treatment 6
Screening for lung disease symptoms (clubbing, persistent cough, shortness of breath) and monitoring with pulmonary function tests and high-resolution CT when indicated is recommended 6
IL-1 or IL-6 inhibitors are not contraindicated in patients with lung disease 6

Early initiation of biologic therapy improves outcomes ("window of opportunity") 6
Treatment should follow a treat-to-target approach with regular disease activity assessment 6
Maintaining clinically inactive disease for at least 6 months off glucocorticoids before considering tapering of biologic therapy is recommended 1
Patients with chronic articular disease generally have worse prognosis and may require more aggressive therapy 5

Relying solely on NSAIDs or glucocorticoids as long-term therapy, as most patients will require more advanced treatment 5, 7
Failing to screen for and promptly treat MAS, which is the most life-threatening complication 6
Overlooking the need for regular monitoring of disease activity and treatment response 1, 6