What is the initial treatment for adult-onset Still's disease?

Initial Treatment for Adult-Onset Still's Disease

IL-1 inhibitors (particularly anakinra) or IL-6 inhibitors (tocilizumab) should be initiated as early as possible—ideally within 3 months of symptom onset—once the diagnosis of adult-onset Still's disease is established. 1

Primary Treatment Recommendation

The 2024 EULAR/PReS guidelines strongly recommend IL-1 or IL-6 inhibitors as first-line therapy based on overwhelming real-world evidence demonstrating their ability to control both systemic and articular manifestations while minimizing glucocorticoid exposure. 1

Choice Between IL-1 and IL-6 Inhibitors

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

The comparative safety data clearly favors IL-1 inhibition:

• Serious adverse events: IL-1 inhibitors show significantly lower rates (22.6 per 100 patient-years) compared to tocilizumab (36.5 per 100 patient-years) 1
• Infectious complications: Total infections are substantially lower with IL-1 inhibitors (94.5 per 100 patient-years) versus tocilizumab (104.6 per 100 patient-years) 1
• Among IL-1 inhibitors, anakinra demonstrates the best safety profile with only 10.4 serious adverse events per 100 patient-years and 18.1 infectious adverse events per 100 patient-years 1

Special consideration: Anakinra is specifically preferred when macrophage activation syndrome is impending or suspected. 2

Timing is Critical: The Window of Opportunity

Initiate biologic therapy before 3 months from symptom onset to optimize outcomes. 1

Real-world observational data demonstrates that early initiation of IL-1 or IL-6 inhibitors:

• Achieves higher rates of clinically inactive disease off glucocorticoids 1
• Decreases the proportion of patients developing chronic persistent disease 1
• Translational data from murine models supports this therapeutic window, showing that early but not late IL-1 inhibition prevents arthritis development and Th17 cell expansion 1

Role of Glucocorticoids

Glucocorticoids may be used temporarily during diagnostic workup or for severe systemic manifestations, but should not be maintained long-term. 1, 2

• Short-term glucocorticoids at low doses (≤0.1 mg/kg/day prednisone equivalent) can be used alongside biologics for moderate disease activity 2
• High-dose glucocorticoids are reserved for life-threatening complications like pericarditis or macrophage activation syndrome 2, 3
• Glucocorticoid dependence must be avoided—if disease control requires ongoing steroids, additional therapy should be added rather than maintaining steroid treatment 1

What NOT to Use as Initial Therapy

NSAIDs alone are inadequate for initial treatment, controlling disease in only 7-15% of patients and should be limited to symptomatic management of fever and arthralgia during diagnostic evaluation. 1

Conventional synthetic DMARDs (like methotrexate) should not be first-line therapy. 1

• The only RCT of methotrexate in Still's disease showed no superiority over placebo even at a low response threshold 1
• These agents are now relegated to settings where IL-1 and IL-6 inhibitors are unavailable 1
• Historical use showed only ~40% overall response rates 1

Treatment Target

The primary goal is clinically inactive disease (CID) off glucocorticoids. 2, 3

• Maintain CID for 3-6 months without glucocorticoids before considering biologic tapering 1, 2
• Regular disease activity assessment with treatment adjustment is mandatory 2, 3

Common Pitfalls to Avoid

Do not delay biologic therapy while attempting prolonged trials of NSAIDs or conventional DMARDs. The evidence clearly shows that 88% of patients eventually require more advanced therapy, and delaying biologics beyond 3 months may worsen long-term outcomes. 1

Do not maintain patients on long-term glucocorticoids as definitive therapy. While 76-95% initially respond to steroids, this approach leads to significant toxicity and does not prevent joint destruction in chronic articular disease. 1

Do not overlook the need to screen for macrophage activation syndrome, which occurs in up to 23% of AOSD patients and represents the most life-threatening complication requiring immediate escalation of therapy. 4